Otevřené Ph.D. pozice

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Neuroscience

TRAK1 and TRAK2 adaptor proteins in brain development and neurodevelopmental disorders

Laboratory name: Molecular Neurobiology

Supervisor (email): Martin Balastik (martin.balastik@fgu.cas.cz)

Laboratory website: Molecular Neurobiology

PhD project: TRAK1 and TRAK2 adaptor proteins in brain development and neurodevelopmental disorders

Mitochondrial transport is essential for nearly all cellular processes but is particularly critical in neurons, where it ensures energy distribution and availability within their long, polarized processes. Dysregulation of microtubule-based mitochondrial transport in neurons has been implicated in numerous neurodevelopmental and neurodegenerative disorders. Mitochondrial transport is tightly regulated by adaptor proteins, and in humans, mutations in the adaptor protein TRAK1 have been linked to severe developmental and epileptic encephalopathies (DEE). Through a large-scale whole-genome and exome sequencing project on DEE patients, we have identified several new TRAK1 and TRAK2 gene variants, underscoring the critical role of both genes in neural development and disease. Additionally, we have generated mouse models with various mutations in TRAK1 gene that exhibit severe developmental encephalopathy, and premature lethality.

In this PhD project, the selected candidate will investigate the effects of TRAK1 and TRAK2 gene variants identified in DEE patients on mitochondrial transport and neural development. Specifically, the project will involve: In vitro studies – characterizing the impact of the identified variants on mitochondrial transport in cultured neurons. In vivo analysis – using in utero electroporation to study the role of these variants in cortical development. Comparative studies – performing phenotypic analyses of TRAK1 and TRAK2 mutant mice to assess their roles in neuron migration, brain connectivity, and function. The project will employ advanced techniques, including microfluidic chambers for neuron cultures, molecular biology methods, and imaging-based assays for mitochondrial transport. The project is supported by Czech Health Research Council grant ensuring comprehensive financial and technical support. This project offers a unique opportunity to elucidate the role of TRAK proteins in mitochondrial transport and their broader implications in neural development and disease.

Candidate’s profile (requirements):

We are seeking outstanding highly motivated candidates with master’s degree or equivalent in molecular biology, biochemistry, physiology, medicine or related fields, or those expecting to obtain their degree this year. Candidates must be fluent in English. Experience with in vivo models (mouse, rat) as well as with in vitro cell cultures and molecular biology techniques are advantage.

References:

Siahaan V., Weissova R., et al, Tau phosphorylation impedes functionality of protective tau envelopes. Nat. Chem. Biol. 2026 Jan 27; 10.1038/s41589-025-02122-9
Gavoci A., et al., Polyglutamylation of microtubules drives neuronal remodeling.

Nat Commun. 2025 Jun 25, 16(1):5384.

Maimon R, et al, A CRMP4-dependent retrograde axon-to-soma death signal in amyotrophic lateral sclerosis EMBO J, 2021, Sep 1;40(17):e107586
Ziak J, et al, CRMP2 mediates Sema3F-dependent axon pruning and dendritic spine remodeling, EMBO Rep, 2020 Mar 4;21(3):e48512.

Rare disease-associated variants in NMDAR genes: impact on synaptic transmission and plasticity

Laboratory: Laboratory of Cellular Neurophysiology

Supervisor: T. Smejkalova, Ph.D. (tereza.smejkalova@fgu.cas.cz)

Laboratory website: Laboratory of Cellular Neurophysiology – FGU

PhD project: Rare disease-associated variants in NMDAR genes: impact on synaptic transmission and plasticity

N-methyl-D-aspartate receptors (NMDARs) are synaptic glutamate receptors with a key role in synaptic plasticity. NMDAR function is therefore critical for the development of neural circuits and for their ability to process and store information. In recent years, changes in GRIN genes encoding NMDAR subunits have been detected in patients with neurodevelopmental disorders typically manifested by developmental delay, intellectual disability, and often some form of epilepsy. Over 700 different disease-associated GRIN gene variants have been identified so far, including several in pediatric patients in the Czech Republic, but how these variants may be involved in disease etiology and what therapeutic interventions may be beneficial for individual patients remains poorly understood.

The selected PhD candidate will use patch-clamp electrophysiology and live-cell Ca²⁺ imaging to study NMDAR function, synaptic transmission and plasticity, and circuit properties in neuronal preparations expressing individual patient GRIN gene variants. The effects of variants on NMDAR assembly and subcellular localization will also be investigated using biochemical methods and high-resolution immunofluorescence microscopy, in part in collaboration with leading experts abroad. The observed functional changes associated with pathogenic GRIN gene variants will be targeted with pharmacological modulation, to test personalized therapy approaches suitable for individual GRIN patients.

Candidate’s profile (requirements):

We are seeking a motivated candidate with a master’s degree or equivalent in genetics, molecular biology, biochemistry, physiology, medicine, or related fields, or a student expecting to obtain their degree this year. Experience with molecular biology techniques, cell culture, animal models, and/or microscopy is an advantage.

References:

Candelas Serra et al. (2024) Characterization of mice carrying a neurodevelopmental disease-associated GluN2B(L825V) variant. Journal of Neuroscience 44(31):e2291232024. doi: 10.1523/JNEUROSCI.2291-23.2024.
Korinek et al. (2024) Disease-associated variants in GRIN1, GRIN2A and GRIN2B genes: Insights into NMDA receptor structure, function, and pathophysiology. Physiological Research 73(Suppl 1):S413-S434. doi: 10.33549/physiolres.935346.
Kysilov, Kuchtiak et al. (2024) Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids. Cellular and Molecular Life Sciences 81(1):36. doi: 10.1007/s00018-023-05062-6.
Smejkalova et al., (2021) Endogenous neurosteroids pregnanolone and pregnanolone sulfate potentiate presynaptic glutamate release through distinct mechanisms. British Journal of Pharmacology 178(19):3888-3904. doi: 10.1111/bph.15529.

The role of Dorsal Root Ganglion (DRG) neurons in neuropathic pain

Laboratory name: Laboratory of Pain Research

Supervisor (email): Jiri Palecek, M.D., Ph.D. (Jiri.Palecek@fgu.cas.cz)

Laboratory website: https://www.fgu.cas.cz/departments/vyzkum-bolesti

PhD project: The role of Dorsal Root Ganglion (DRG) neurons in neuropathic pain

The main research interest of our department is to study mechanisms of pain and to explore new possibilities of pain treatment, especially in chronic states. Our experimental work is concentrated on the modulation of nociceptive information at the spinal cord level that is the first relay center between the periphery and higher brain areas. Our goal is to study these modulatory mechanisms in order to improve therapy for pain conditions such as neuropathic and cancer related pain. This PhD project will be focused to study properties of different types of DRG neurons, their role in peripheral and spinal mechanisms of acute and especially chronic pain syndromes. Properties of DRG neurons will be studied using electrophysiological, optogenetic, OMICS analysis, functional imaging, immunohistochemical, molecular and behavioral methods. Different models of pathological states of chemotherapy, nerve injury and diabetes induced neuropathy will be employed. The goal will be also to introduce cultivation of human pluripotent stem cells (iPSCs) and their differentiation into nociceptors and potentially also human DRG neurons, for their direct comparison with rodent DRG cells. The research is supported by several ongoing grant projects. The PhD program will be conducted at the Faculty of Science at the Charles University in Prague and the dissertation work will be conducted at the Institute of Physiology, Czech Academy of Science in Prague.

Candidate’s profile (requirements):

The candidate should have a Masters‘ degree in biological, medical or chemical sciences, or be due to complete their studies in this academic year. Experience in physiology, neurophysiology, cell biology, molecular biology or electrophysiology techniques would be an advantage. Candidates should be fluent in Czech or English.

Selected References:

Nerandzic V, Mrozkova P, Adamek P, Spicarova D, Nagy I, Palecek J. Peripheral inflammation affects modulation of nociceptive synaptic transmission in the spinal cord induced by N-arachidonoylphosphatidylethanolamine. British Journal of Pharmacology 2018, 175, 2322-2356. IF = 6.8

Adamek P, Heles M, Palecek J, Mechanical allodynia and enhanced responses to capsaicin are mediated by PI3K in paclitaxel model of peripheral neuropathy. Neuropharmacology. 2019,146:163-174. IF=4.3

Heleš M, Mrózková P, Šulcová D, Adámek P, Špicarová D, Paleček J. Chemokine CCL2 prevents opioid-induced inhibition of nociceptive synaptic transmission in spinal cord dorsal horn. Journal of Neuroinflammation. 2021; 18(1)); 279 . IF = 9.6

Adamek, M. Heles, A. Bhattacharyya, M. Pontearso, J. Slepicka, J. Palecek. Dual PI3K-δ/γ Inhibitor Duvelisib Prevents Development of Neuropathic Pain in Model of Paclitaxel-Induced Peripheral Neuropathy. Journal of Neuroscience. 2022 Mar 2; 42(9):1864-1881. IF=6.7

Spicarova D, Nerandzic V, Muzik D, Pontearso M, Bhattacharyya A, Nagy I and Palecek J. Inhibition of synaptic transmission by anandamide precursor 20:4-NAPE is mediated by TRPV1 receptors under inflammatory conditions. Frontiers in Mol. Neuroscience 2023, 16:1188503,1-11, 2023, IF = 6.2.

Pontearso M, Slepička J, Bhattacharyya A, Špicarová D, Paleček J. Dual effect of anandamide on spinal nociceptive transmission in control and inflammatory conditions. Biomedicine & Pharmacotherapy. 2024; 173(April); 116369. IF=7,5

Mechanisms of neuropathic pain

Laboratory name: Laboratory of Pain Research

Supervisor (email): Diana Spicarova, Ph.D. (Diana.Spicarova@fgu.cas.cz

Laboratory website: https://www.fgu.cas.cz/departments/vyzkum-bolesti

PhD project: Mechanisms of neuropathic pain

The primary research interest of our laboratory is to investigate the mechanisms of pain and to explore new possibilities for its treatment, with a particular focus on neuropathic conditions. Our experimental work focuses on the modulation of nociceptive information at the dorsal root ganglia (DRG) and the spinal cord, which serve as the primary relay center between the periphery and higher brain areas. Our goal is to study these modulatory mechanisms to improve therapy for pain conditions such as neuropathic pain, including cancer-related conditions. This project will introduce the cultivation of human pluripotent stem cells (iPSCs) and their differentiation into nociceptors as a model of human DRG neurons. The emphasis of this project will be on the comparison of the rodent and human DRG. Further, the modulation of nociceptive synaptic transmission at synapses formed by the central ending of DRG neurons and spinal neurons will be studied in acute spinal cord slices. Mainly, electrophysiological, optogenetic, calcium imaging, OMICS analysis, molecular, immunohistochemical, and behavioral methods will be used. In collaboration with clinics, we aim to investigate human pathology in patients with pain. Several ongoing grants support our research. The PhD program will be conducted at the Faculty of Science of Charles University in Prague, and the dissertation work will be carried out at the Institute of Physiology, Czech Academy of Sciences in Prague.

Candidate’s profile (requirements):

The candidate should have a Master’s degree in biological, medical, or chemical sciences, or be due to complete their studies in this academic year. Experience in physiology, neurophysiology, cell biology, molecular biology, or electrophysiology techniques would be an advantage. Candidates should be fluent in Czech or English.

Selected References:

Nerandzic V, Mrozkova P, Adamek P, Spicarova D, Nagy I, Palecek J. Peripheral inflammation affects modulation of nociceptive synaptic transmission in the spinal cord induced by N-arachidonoylphosphatidylethanolamine. British Journal of Pharmacology 2018, 175, 2322-2356. IF = 6.8

Adamek P, Heles M, Palecek J, Mechanical allodynia and enhanced responses to capsaicin are mediated by PI3K in paclitaxel model of peripheral neuropathy. Neuropharmacology. 2019,146:163-174. IF=4.3

Heleš M, Mrózková P, Šulcová D, Adámek P, Špicarová D, Paleček J. Chemokine CCL2 prevents opioid-induced inhibition of nociceptive synaptic transmission in spinal cord dorsal horn. Journal of Neuroinflammation. 2021; 18(1)); 279 . IF = 9.6

Adamek, M. Heles, A. Bhattacharyya, M. Pontearso, J. Slepicka, J. Palecek. Dual PI3K-δ/γ Inhibitor Duvelisib Prevents Development of Neuropathic Pain in Model of Paclitaxel-Induced Peripheral Neuropathy. Journal of Neuroscience. 2022 Mar 2; 42(9):1864-1881. IF=6.7

Spicarova D, Nerandzic V, Muzik D, Pontearso M, Bhattacharyya A, Nagy I and Palecek J. Inhibition of synaptic transmission by anandamide precursor 20:4-NAPE is mediated by TRPV1 receptors under inflammatory conditions. Frontiers in Mol. Neuroscience 2023, 16:1188503,1-11, 2023, IF = 6.2.

Pontearso M, Slepička J, Bhattacharyya A, Špicarová D, Paleček J. Dual effect of anandamide on spinal nociceptive transmission in control and inflammatory conditions. Biomedicine & Pharmacotherapy. 2024; 173(April); 116369. IF=7,5

Neuronal-type-specific targeting of nAChRs using a pair of nitroreductase and masked nicotinic ligands

Laboratory name: Laboratory of Cholinergic Signaling

Supervisor (email): Helena Janickova, MD, PhD, helena.janickova@fgu.cas.cz

Laboratory website

PhD project: Neuronal-type-specific targeting of nAChRs using a pair of nitroreductase and masked nicotinic ligands

Nicotinic acetylcholine receptors (nAChRs) are implicated in autism and other neuropsychiatric disorders, but it is challenging to use them as a therapeutic target. One of the reasons is their widespread distribution in the brain and thus the difficulty in controlling them selectively in circuits and neurons where needed. The present project aims to develop a new approach for the neuronal-type-specific targeting of nAChRs using a pair of an engineered bacterial enzyme nitroreductase and a nicotinic ligand masked with a nitroaryl group. We collaborate with a lab of organic synthesis on the preparation of the masked ligands. The PhD student will test the nicotinic activity of the masked compounds in vitro and their distribution by fluorescence in vitro and in vivo. The selective unmasking of the compounds and their ability to alter nicotinic expression will be ultimately tested in vivo.

Candidate’s profile (requirements):

(brief description of the required background of the applicants, i.e. education, title, languages, etc.)

We are looking for a self-motivated candidate with a master’s degree in molecular biology, biochemistry, physiology, medicine or related fields. Experience with organic synthesis, neuronal cultures, viral vectors and/or handling mice is advantageous. The successful candidate is supposed to spend a significant time of his/her PhD studies in a collaborating laboratory(ies). Therefore, the willingness to travel and fluency in English is essential.

References:

Abbondanza A, Ribeiro Bas I, Modrak M, Capek M, Minich J, Tyshkevich A, Naser S, Rangotis R, Houdek P, Sumova A, Dumas S, Bernard V, Janickova H.: Nicotinic acetylcholine receptors expressed by striatal interneurons inhibit striatal activity and control striatal-dependent behaviors. J Neurosci. 2022, 42: 2786-2803.
Urushadze A, Janicek M, Abbondanza A, Janickova H.: Timed sequence task: a new paradigm to study motor learning and flexibility in mice. eNeuro. 2023, 10: ENEURO.0145-23.2023.
Abbondanza A, Urushadze A, Alves-Barboza AR, Janickova H.: Expression and function of nicotinic acetylcholine receptors in specific neuronal populations: Focus on striatal and prefrontal circuits. Pharmacol Res. 2024, 204: 107190.

Neuroinflammation and pain

Laboratory name: Laboratory of Pain Research

Supervisor (email): Jiri Palecek, M.D., Ph.D. (Jiri.Palecek@fgu.cas.cz)

Laboratory website: https://www.fgu.cas.cz/departments/vyzkum-bolesti

PhD project: Neuroinflammation and pain

The main research interest of our department is to study mechanisms of pain and to explore new possibilities of pain treatment, especially in chronic states. Our experimental work is concentrated on the modulation of nociceptive information at the spinal cord level that is the first relay center between the periphery and higher brain areas. Our goal is to study these modulatory mechanisms in order to improve therapy for pain conditions such as neuropathic and cancer related pain. This PhD project will be focused on the role of neuroinflammation in modulation of synaptic transmission and chronic pain development. It will study the role of TRPV1 receptors, cannabinoids, endogenous lipids, opioids and inflammatory cytokines in this process. The student will use mainly electrophysiological, optogenetic, OMICS analysis, functional imaging, immunohistochemical, molecular and behavioral methods. In collaboration with clinics we will aim to study also human pathology in pain patients. Our research is supported by several ongoing grant projects. The PhD program will be conducted at the Faculty of Science at the Charles University in Prague and the dissertation work will be conducted at the Institute of Physiology, Czech Academy of Science in Prague.

Candidate’s profile (requirements):

Selected References:

Adamek, M. Heles, A. Bhattacharyya, M. Pontearso, J. Slepicka, J. Palecek. Dual PI3K-δ/γ Inhibitor Duvelisib Prevents Development of Neuropathic Pain in Model of Paclitaxel-Induced Peripheral Neuropathy. Journal of Neuroscience. 2022 Mar 2; 42(9):1864-1881. IF=6.7

Genetic tools for circadian clock disruption in non-neural brain tissues studied by luminescence microscopy

Laboratory name: Laboratory of Biological rhythms

Supervisor (email): Martin Sladek, Ph.D. (martin.sladek@fgu.cas.cz)

Laboratory website: https://fgu.cas.cz/en/research-and-laboratories/research-departments/laboratory-of-biological-rhythms/

PhD project: Genetic tools for circadian clock disruption in non-neural brain tissues studied by luminescence microscopy

Key words: circadian, rhythms, AAV, gene knockdown, clock, choroid plexus, cerebrospinal fluid, mouse, lipidomics, metabolomics, microscopy

Introduction

Irregular daily regime, sleep deprivation and misalignment between eating schedules and light-dark cycle disrupt the circadian system. The project will study one of the potential molecular mechanisms of how these factors may negatively affect health. It will focus on non-neural brain structures, particularly on choroid plexus (ChP), which is the source of cerebrospinal fluid (CSF) in brain ventricles. ChP has recently attracted significant attention in the neuroscience field due to its involvement in brain homeostasis and the pathophysiology of neuropsychiatric disorders [1]. Importantly, as was shown by our laboratory [2] and others [3], ChP contains a robust circadian clock that rhythmically regulates its physiological functions.

The circadian rhythm is generated at the cellular level. The molecular core clock mechanism is formed by transcriptional-translational feedback loops that employ a set of clock genes [4]. Most components of the core clock mechanism are rhythmically expressed and serve as regulators of downstream clock-controlled genes, resulting in an array of rhythmic functions. In mammals, only the central clock in the suprachiasmatic nucleus (SCN) of the hypothalamus [5] receives information about the light/dark (LD) cycle to synchronize with external time and entrain the clocks in other tissues, both in the brain and on the periphery. Unlike the SCN, these downstream clocks are also more or less sensitive to timing of food. Misalignment between the LD cycle, sleep/wake, and feeding/fasting cycles is the major contributor to the uncoupling of the peripheral clocks from the SCN [6].

Objective

Our recent data show that ChP clock is highly sensitive to circadian misalignment [7], feeding regime [8] and glucocorticoids [2, 9]. The objective of this project is to provide mechanistic insights into the circadian regulation of the ChP functions. Specifically, we hypothesize that circadian system modulates the CSF production, composition and brain waste clearance via the ChP clock. For testing these hypotheses, we need genetic tools and efficient delivery systems.

Specific aims

Genetic tools to disrupt circadian clock and in vitro testing

pAAV-U6-Arntl-shRNA-EGFP or similar vector will be used to prepare adeno-associated virus (AAV) serotype 5 virions using a commercial supplier (Vectorbuilder). The ability of the AAVs to downregulate essential circadian clock gene Arntl/Bmal1 and dampen the clock will be tested on NIH3T3 cell line stably expressing luciferase reporter under the control of Per2 or Nr1d1 promoter using continuous monitoring of circadian luminescence in plate reader Luminoskan Ascent and by RT qPCR analysis of clock gene expression. As the AAV5 serotype may show low efficiency in transduction of cell lines, AAVs will be additionally applied on top of ChP explants from mPer2Luc mice that will then be imaged using combined luminescence (PER2::LUC) and fluorescence (GFP) microscopy (Olympus LV200). The effect on the clock and transduction efficiency will be quantified. Use of CRISPR-Cas9, Cre-Lox or enhancer AAVs will be considered to attain high cell-type specificity. Additional serotypes may be tested for other extra SCN oscillators. Non-mammalian or scrambled shRNA AAV5 will be used as negative control.

Examine the role of the circadian clock in ChP function in vivo

We shall inject AAV5 virions into the 4th ventricle of transgenic mPer2Luc (B6.129S6-Per2tm1Jt/J, JAX, bred at the IPHYS) mice to downregulate Bmal1 (Arntl) and disrupt the circadian clock in the ChP in vivo. According to published data, AAV5 selectively infects epithelial cells when injected i.c.v. [10].

a) Pilot animal experiment. Stereotaxic surgery and AAV transduction will be performed by i.c.v. delivery of at least 2.5 ul of 10E13 purified virions from VectorBuilder into the 4th ventricle under deep anesthesia. In a pilot experiment, AAV virions performance will be assessed ex vivo using GFP fluorescence to check transduction. The bioluminescence recording (Lumicycle apparatus, Olympus LV200 microscope) of PER2 levels of ChP organotypic explants from mPer2Luc mice will be used to check shRNA ability to disrupt clock and compared with non-mammalian shRNA negative control.
b) Main animal experiment. Experimental and negative control group of mPer2Luc mice will be injected with AAV virions as detailed above. Four to five weeks later, locomotor activity monitored for 2-3 weeks under constant darkness (DD) will reveal whether the absence of the ChP clock affects the properties of the central clock in the SCN (period, amplitude). Then, mice re-entrained to LD12:12, will be sacrificed at regular time intervals and CSF will be collected for lipidomics and metabolomics assay, samples of ChP, SCN and hippocampus will be dissected for RT qPCR analysis of genes of interest. A separate group of mice will be tested for blood-CSF barrier permeability – mice will be intravenously injected with 4 kDa FITC-dextran 15 min before CSF isolation by cisterna magna puncture, 1 ul of CSF will be diluted in 99 μl PBS and fluorescence will be measured using the fluorescence reader (kex/kem = 485/520 nm).

Expected results: The results will show whether local clocks are needed for various ChP functions. In addition, the result will confirm that disturbance of the ChP clock in vivo affects the central clock in the SCN, as shown by [2].

Outcome

PhD student will be the first author on at least one paper and co-author on two additional papers, focusing on the role of the ChP clock in regulating mouse locomotor behavior, CSF production and composition, blood-brain barrier permeability and the impact on other brain clocks, including the central clock in the SCN.

PhD student will be trained in mouse brain tissue sampling, actigraphy, molecular biology methods (RNA isolation, RT qPCR, cloning), tissue culture (organotypic explants, AAV transduction), bioluminescence methods (real-time detection of circadian gene expression), fluorescence and luminescence microscopy (including time-series image processing), lipidomic and metabolomic bioinformatics, including various rhythm detection algorithms.

Literature

Stopa, E.G., et al., Fluids Barriers CNS, 2018. 15(1): 18.
Sladek, M., et al., Fluids Barriers CNS, 2024. 21(1): 46.
Myung, J., et al., Nat Commun, 2018. 9(1): 1062.
Mohawk, J.A., C.B. Green, and J.S. Takahashi, Annu Rev Neurosci, 2012. 35: 445-62.
Hastings, M.H., E.S. Maywood, and M. Brancaccio, Nat Rev Neurosci, 2018. 19(8): 453-469.
Albrecht, U., Neuron, 2012. 74(2): 246-60.
Drapsin, M., et al., Brain Behav Immun, 2024. 117: 255-269.
Dockal, T., et al., Cell Mol Life Sci, 2025. 82(1): 247.
Liska, K., et al., J Endocrinol, 2021. 248(2): 155-166.
Mazucanti, C.H., et al., Cell Rep, 2023. 42(8): 112903.

Candidate’s profile (requirements):

(brief description of the required background of the applicants, i.e. education, title, languages, etc.)

Molecular biology background, good ENG language skills (or CZ with usable ENG), Masters/MD or equivalent

References:

Sladek, M., et al., Fluids Barriers CNS, 2024. 21(1): 46. 10.1186/s12987-024-00547-3

Dockal, T., et al., Cell Mol Life Sci, 2025. 82(1): 247. 10.1007/s00018-025-05798-3

Liska, K., et al., J Endocrinol, 2021. 248(2): 155-166. 10.1530/JOE-20-0526

Sladek, M., et al., PLoS Biol, 2025. 23(9): e3003404. 10.1371/journal.pbio.3003404

Molecular regulation of Mitochondrial Transport and Neural Development

Laboratory name: Molecular Neurobiology

Supervisor (email): Martin Balastik, Ph.D., (Martin.Balastik@fgu.cas.cz)

Laboratory website

PhD project: Molecular regulation of Mitochondrial Transport and Neural Development

In this PhD project, the selected student will investigate the effects of TRAK1 and TRAK2 gene variants identified in DEE patients on mitochondrial transport and neural development. Specifically, the project will involve: In vitro studies – characterizing the impact of the identified variants on mitochondrial transport in cultured neurons. In vivo analysis – using in utero electroporation to study the role of these variants in cortical development. Comparative studies – performing phenotypic analyses of TRAK1 and TRAK2 mutant mice to assess their roles in neuron migration, brain connectivity, and function. The project will employ advanced techniques, including microfluidic chambers for neuron cultures, molecular biology methods, and imaging-based assays for mitochondrial transport. The project is supported by funding from the Czech Science Foundation and from project Exceles Neur-IN ensuring comprehensive financial and technical support. This project offers a unique opportunity to elucidate the role of TRAK proteins in mitochondrial transport and their broader implications in neural development and disease.

Candidate’s profile (requirements):

We are seeking outstanding self-motivated candidates with master’s degree or equivalent in molecular biology, biochemistry, physiology, medicine or related fields, or those expecting to obtain their degree this year. Candidates must be fluent in English. Experience with in vivo models (mouse, rat) as well as with in vitro cell cultures and molecular biology techniques are advantage.

References:

Maimon R, et al, A CRMP4-dependent retrograde axon-to-soma death signal in amyotrophic lateral sclerosis EMBO J, 2021, Sep 1;40(17):e107586
Ziak J, et al, CRMP2 mediates Sema3F-dependent axon pruning and dendritic spine remodeling, EMBO Rep, 2020 Mar 4;21(3):e48512.

Multidisciplinary study of neurodevelopmental disorders associated with variants in NMDA receptor genes

Laboratory: Cellular Neurophysiology

Head of the Laboratory: Prof. L. Vyklický MD, PhD, DSc

Supervisors: Aleš Balík, PhD (ales.balik@fgu.cas.cz) or Tereza Smejkalová, PhD (tereza.smejkalova@fgu.cas.cz)

Laboratory Website

PhD Project: Multidisciplinary study of neurodevelopmental disorders associated with variants in NMDA receptor genes

N-methyl-D-aspartate receptors (NMDARs) are synaptic glutamate receptors with a key role in synaptic plasticity. NMDAR function is therefore critical for the development of neural circuits and for their ability to process and store information. In recent years, changes in GRIN genes encoding NMDAR subunits have been detected in patients with neurodevelopmental disorders typically manifested by developmental delay, intellectual disability, and often some form of epilepsy. Over 700 different disease-associated GRIN gene variants have been identified so far, including 9 found in pediatric patients in the Czech Republic, but how these variants may be involved in disease etiology and what therapeutic interventions may be beneficial for individual patients remains poorly understood.

The selected PhD candidate will work on one of the sub-topics: (1) Using bioinformatics approaches and molecular biology techniques we will investigate the possible link between GRIN gene variants and the genetic background of patients and to study the effects of variants on the regulation of other GRIN genes and the possible presence of specific genetic compensatory mechanisms. (2) Using biochemistry and immunofluorescence microscopy we will assess the effects of variants on NMDAR assembly and subcellular localization. (3) Using patch-clamp electrophysiology and live-cell Ca²⁺ imaging we will study NMDAR function, synaptic transmission and plasticity, and network activity in neuronal preparations expressing individual patient GRIN gene variants. Results of this work will improve our understanding of the complex nature of GRIN disorders and help guide precision therapy approaches suitable for individual GRIN patients.

Candidates’ Profile (requirements):

We are seeking motivated candidate/s with a master’s degree or equivalent in genetics, bioinformatics, molecular biology, biochemistry, physiology, medicine or related fields, or a student expecting to obtain their degree this year. Experience with molecular biology techniques, cell culture, animal models, microscopy and/or work with bioinformatics tools is an advantage.

References:

Candelas Serra et al. (2024) Characterization of Mice Carrying a Neurodevelopmental Disease Associated GluN2B (L825V) Variant. J Neurosci. 44(31):e2291232024.

Korinek et al. (2024) Disease-Associated Variants in GRIN1, GRIN2A and GRIN2B genes: Insights into NMDA Receptor Structure, Function, and Pathophysiology. (Review) Physiol Res. 73(Suppl 1):S413-S434.

Kysilov et al. (2024) Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids. Cell Mol Life Sci. 81(1):36.

Kysilov et al. (2022) Pregnane-based steroids are novel positive NMDA receptor modulators that may compensate for the effect of loss-of-function disease-associated GRIN mutations. Br J Pharmacol. 179(15):3970-3990.

Smejkalova et al. (2021) Endogenous neurosteroids pregnanolone and pregnanolone sulfate potentiate presynaptic glutamate release through distinct mechanisms. Br J Pharmacol. 178(19):3888-3904.

Hirschfeldova et al. (2021) Evidence for the Association between the Intronic Haplotypes of Ionotropic Glutamate Receptors and First-Episode Schizophrenia. J Pers Med. 11(12):1250.

Mechanisms of selective modulation of individual subtypes of muscarinic receptors

Laboratory name: Neurochemistry

Supervisor (email): Jan Jakubík, jan.jakubik@fgu.cas.cz

Laboratory website

PhD project: Mechanisms of selective modulation of individual subtypes of muscarinic receptors

Altered muscarinic signalling is frequently involved in neurological and psychiatric diseases as well as diseases of internal organs. To target a particular condition, selective modulation of individual muscarinic subtypes is necessary to avoid side effects. High homology of the orthosteric binding site among all muscarinic subtypes makes a finding of orthosteric ligands that bind selectively to individual muscarinic subtypes virtually unattainable. Allosteric ligands modulate binding of orthosteric ligands and functional response to agonists from less-conserved sites on the receptor. Dualsteric ligands employ both orthosteric and allosteric sites. The aim of this project is structure-guided development of novel selective allosteric and dualsteric ligands.

Candidate’s profile (requirements):

We are seeking highly motivated independent candidate with a master’s degree or equivalent in pharmacology, biochemistry, molecular biology or related fields, or those expecting to obtain their degree this year. Essentially, candidate should be fluent in English and willing to travel to collaborating laboratories abroad to learn new techniques required for this project. Experience with in vitro cell culture, molecular biology techniques and basic programming skills are an advantage.

References:

Nelic D et al. Agonist-selective activation of individual G-proteins by muscarinic receptors. Sci Rep ;14(1):9652. doi:10.1038/s41598-024-60259-4
Jakubík J et al. The operational model of allosteric modulation of pharmacological agonism. Sci Rep 2020;10(1):14421. doi: 10.1038/s41598-020-71228-y
Randáková A and Jakubík J, Functionally selective and biased agonists of muscarinic receptors. Pharmacol Res. 2021;169:105641. doi: 10.1016/j.phrs.2021.105641
Randáková A, et al, Novel long-acting antagonists of muscarinic ACh receptors. Br J Pharmacol. 2018; 175(10):1731-1743. doi: 10.1111/bph.14187

Nicotinic acetylcholine receptors in prefrontal neuronal populations and their role in the control of ASD-like behavioral symptoms

Laboratory name: Laboratory of Cholinergic Signaling

Supervisor (email): Helena Janickova, MD, PhD (helena.janickova@fgu.cas.cz)

Laboratory website

PhD project: Nicotinic acetylcholine receptors in prefrontal neuronal populations and their role in the control of ASD-like behavioral symptoms

Nicotinic acetylcholine receptors (nAChRs) are implicated in autism spectrum disorders (ASD) and other neuropsychiatric disorders, but it is challenging to use them as an effective therapeutic target. One of the reasons is their widespread distribution in the brain and thus the difficulty in controlling them selectively in circuits and neurons where needed. The present project aims to determine whether the selective modulation of nAChRs in specific neuronal types is more effective in the control of ASD-like behavioral symptoms in mice compared to non-selective nicotinic modulation. To this aim, students will analyze the expression of the most common nAChR subtypes in individual neuronal populations in the mouse prefrontal cortex using RNAscope and FISH. They will then manipulate the expression of the receptors in specific neurons by shRNA and CRISPR. Finally, the effect of these manipulations will be examined by behavioral testing in automated touchscreen-equipped operant boxes, and the effect on neuronal activity will be assessed by imaging techniques.

Candidate’s profile (requirements):

(brief description of the required background of the applicants, i.e. education, title, languages, etc.)

We are looking for a self-motivated candidate with a master’s degree in molecular biology, biochemistry, physiology, medicine or related fields. Experience with cloning, viral vectors, calcium imaging and/or handling mice is advantageous. The successful candidate is supposed to spend a certain period of time in his/her PhD studies in a collaborating laboratory(ies). Therefore, the willingness to travel and fluency in English is essential.

References:

Abbondanza A, Ribeiro Bas I, Modrak M, Capek M, Minich J, Tyshkevich A, Naser S, Rangotis R, Houdek P, Sumova A, Dumas S, Bernard V, Janickova H.: Nicotinic acetylcholine receptors expressed by striatal interneurons inhibit striatal activity and control striatal-dependent behaviors. J Neurosci. 2022, 42: 2786-2803.
Urushadze A, Janicek M, Abbondanza A, Janickova H.: Timed sequence task: a new paradigm to study motor learning and flexibility in mice. eNeuro. 2023, 10: ENEURO.0145-23.2023.
Abbondanza A, Urushadze A, Alves-Barboza AR, Janickova H.: Expression and function of nicotinic acetylcholine receptors in specific neuronal populations: Focus on striatal and prefrontal circuits. Pharmacol Res. 2024, 204: 107190.

Neuronal-type-specific targeting of nAChRs using a pair of nitroreductase and masked nicotinic ligands

Laboratory name: Laboratory of Cholinergic Signaling

Supervisor (email): Helena Janickova, MD, PhD, helena.janickova@fgu.cas.cz

Laboratory website

PhD project: Neuronal-type-specific targeting of nAChRs using a pair of nitroreductase and masked nicotinic ligands

Candidate’s profile (requirements):

(brief description of the required background of the applicants, i.e. education, title, languages, etc.)

References:

Abbondanza A, Ribeiro Bas I, Modrak M, Capek M, Minich J, Tyshkevich A, Naser S, Rangotis R, Houdek P, Sumova A, Dumas S, Bernard V, Janickova H.: Nicotinic acetylcholine receptors expressed by striatal interneurons inhibit striatal activity and control striatal-dependent behaviors. J Neurosci. 2022, 42: 2786-2803.
Urushadze A, Janicek M, Abbondanza A, Janickova H.: Timed sequence task: a new paradigm to study motor learning and flexibility in mice. eNeuro. 2023, 10: ENEURO.0145-23.2023.
Abbondanza A, Urushadze A, Alves-Barboza AR, Janickova H.: Expression and function of nicotinic acetylcholine receptors in specific neuronal populations: Focus on striatal and prefrontal circuits. Pharmacol Res. 2024, 204: 107190.

Neuroinflammation and pain

Laboratory name: Pain Research

Supervisor (email): Jiri Palecek, M.D., Ph.D., jiri.palecek@fgu.cas.cz

Laboratory website

PhD Project: Neuroinflammation and pain

The main research interest of our department is to study mechanisms of pain and to explore new possibilities of pain treatment, especially in chronic states. Our experimental work is concentrated on the modulation of nociceptive information at the spinal cord level that is the first relay center between the periphery and higher brain areas. Our goal is to study these modulatory mechanisms in order to improve therapy for pain conditions such as neuropathic and cancer related pain. This project will be focused on the role of neuroinflammation in modulation of synaptic transmission and chronic pain development. Lately we are interested in the role of TRPV1 receptors, cannabinoids, endogenous lipids, opioids and inflammatory cytokines in this process. In our research we use mainly electrophysiological, optogenetic, OMICS analysis, functional imaging, immunohistochemical, molecular and behavioral methods. In collaboration with clinics we aim to study human pathology in pain patients. Our research is supported by several ongoing grant projects.

Candidate Requirements: The candidate should have a Masters‘ degree in biological, medical or chemical sciences, or be due to complete their studies in this academic year. Experience in physiology, neurophysiology, cell biology, molecular biology or electrophysiology techniques would be an advantage. Candidates should be fluent in Czech or English.

References:

Li Y, Adamek P, Zhang H, Tatsui CE, Rhines LD, Mrozkova P, Li Q, Kosturakis AK, Cassidy, Harrison,.Cata,P. Sapire,K. Zhang,H. Kennamer, R. M. Jawad, A.B. Ghetti, Yan, J., Paleček, J. Dougherty, P. M. The Cancer Chemotherapeutic Paclitaxel Increases Human and Rodent Sensory Neuron Responses to TRPV1 by Activation of TLR4. J Neurosci. 2015;35(39):13487-13500. IF=6.3

Uchytilová; E, Špicarová D, Paleček J. Hypersensitivity Induced by Intrathecal Bradykinin Administration Is Enhanced by N-oleoyldopamine (OLDA) and Prevented by TRPV1 Antagonist. Int. J. Mol. Sci. 2021; 22(7)); 3712. IF = 6.2

Adamek, M. Heles, A. Bhattacharyya, M. Pontearso, J. Slepicka, J. Palecek. Dual PI3K-δ/γ Inhibitor Duvelisib Prevents Development of Neuropathic Pain in Model of Paclitaxel-Induced Peripheral Neuropathy. Journal of Neuroscience. 2022 Mar 2; 42(9):1864-1881. IF=6.7

Circadian disruption in non-neural brain tissue studied by integrative omics and luminescence microscopy

Laboratory name: Biological rhythms

Supervisor (email): Martin Sládek (martin.sladek@fgu.cas.cz)

Laboratory website

PhD project: Circadian disruption in non-neural brain tissue studied by integrative omics and luminescence microscopy

The project will focus on non-neural brain structures, particularly on choroid plexus (ChP), a crucial tissues for brain homeostasis and the pathophysiology of neuropsychiatric disorders, due to it being the main source of cerebrospinal fluid (CSF) in brain ventricles. ChP contains a robust circadian clock that rhythmically regulates its physiological functions. ChP clock is highly sensitive to circadian clock disruption (CD) by light, mistimed feeding or glucocorticoids. We hypothesize that CD impairs the CSF production, composition and brain waste clearance via the ChP clock and that timed feeding regime can ameliorate its negative impact.

We will use transgenic mice of both sexes with circadian reporter to study the effects of CD on ChP organotypic explants with bioluminescence microscopy. We will compare control, experimental (CD) and intervention (CD with restricted feeding) groups of mice, sampling CSF and ChP around the clock and analyzing circadian rhythms by lipidomics, metabolomics and transcriptomics. We will employ single-cell RNAseq (Chromium) to identify cell-specific changes in RNA levels in response to CD. We will also analyze locomotor activity and blood-CSF barrier permeability. PhD student will be trained among other things in tissue culture, molecular biology methods and bioinformatics.

Candidate’s profile (requirements):

Background in molecular biology, genetics, or cell biology; Masters (Mgr.) degree; English; familiarity with at least one of the following: either molecular biology methods (PCR), or cell culture (sterile work), or bioinformatics, or Python/R.

References:

SLADEK, M., P. HOUDEK, J. MYUNG, K. SEMENOVYKH, T. DOCKAL AND A. SUMOVA The circadian clock in the choroid plexus drives rhythms in multiple cellular processes under the control of the suprachiasmatic nucleus. Fluids Barriers CNS, May 27 2024, 21(1), 46. IF 7.3

DRAPSIN, M., T. DOCKAL, P. HOUDEK, M. SLADEK, K. SEMENOVYKH AND A. SUMOVA Circadian clock in choroid plexus is resistant to immune challenge but dampens in response to chronodisruption. Brain, Behavior, and Immunity, Mar 2024, 117, 255-269. IF 15.1

SLADEK, M., J. KLUSACEK, D. HAMPLOVA AND A. SUMOVA Population-representative study reveals cardiovascular and metabolic disease biomarkers associated with misaligned sleep schedules. Sleep, Jun 13 2023, 46(6), zsad037. IF 5.6

GREINER, P., P. HOUDEK, M. SLADEK AND A. SUMOVA Early rhythmicity in the fetal suprachiasmatic nuclei in response to maternal signals detected by omics approach. PLoS Biology, May 2022, 20(5), e3001637. IF 9.8

INVESTIGATING CIRCULAR RNAS AND M6A METHYLATION LANDSCAPE IN ALZHEIMER’S DISEASE

Laboratory name: Neuroepigenetics
Supervisor (email): Lalit Kaurani (dr.lalit.kaurani@gmail.com)

PhD Project: Investigating circular RNAs and m6A methylation landscape in Alzheimer’s disease

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline, driven by synaptic dysfunction, amyloid-beta plaques, and tau tangles. Recent advances have highlighted the role of non-coding RNAs in neuronal function and disease; however, circular RNAs (circRNAs) remain a largely unexplored class of regulatory molecules in AD pathology. CircRNAs are highly enriched in the brain, dynamically regulated during development, and implicated in synaptic plasticity. Furthermore, m6A methylation, an epitranscriptomic modification, has emerged as a key regulator of circRNA stability and function. This study will investigate the role of circRNAs and their m6A methylation in AD pathology, with a particular focus on synaptic function and disease progression. Specifically, the PhD candidate will profile circRNA expression and m6A modification patterns in post-mortem human AD brain tissues using RNA sequencing and epitranscriptomic approaches. Additionally, the candidate will characterize the functional impact of differentially expressed/methylated circRNAs in neuronal and glial models derived from human iPSCs. Finally, in vivo models will be used to assess how candidate circRNAs influence neuronal function, synaptic plasticity, and behavioral deficits relevant to AD.

Candidate’s profile (requirements):

We are looking for a highly motivated candidate with an MSc degree or equivalent in molecular biology, neuroscience, genetics, biochemistry, or a related field, or one who expects to graduate this year. The candidate must be proficient in English, both written and spoken. They should have a strong interest in neurodegenerative diseases and RNA biology. The ideal candidate should have experience in molecular biology techniques. Experience with bioinformatics, in vivo models, and in vitro cell cultures, particularly neuronal or glial models, is an advantage.

References:

Krüger DM, Pena-Centeno T, Liu S, Park T, Kaurani L, Pradhan R, et al. The plasma miRNAome in ADNI: Signatures to aid the detection of at-risk individuals. Alzheimers Dement. 2024 Nov;20(11):7479–94.

Kaurani L, Islam MR, Heilbronner U, Krüger DM, Zhou J, Methi A, et al. Regulation of Zbp1 by miR-99b-5p in microglia controls the development of schizophrenia-like symptoms in mice. EMBO J. 2024 Apr;43(8):1420–44.

Castro-Hernández R, Berulava T, Metelova M, Epple R, Peña Centeno T, Richter J, Kaurani L, et al. Conserved reduction of m6A RNA modifications during aging and neurodegeneration is linked to changes in synaptic transcripts. PNAS. 2023 Feb 28;120(9):e2204933120.

Islam MR*, Kaurani L*, Berulava T, Heilbronner U, Budde M, Centeno TP, et al. A microRNA signature that correlates with cognition and is a target against cognitive decline. EMBO Mol Med. 2021 Nov 8;13(11):e13659.

Wendeln AC, Degenhardt K, Kaurani L, Gertig M, Ulas T, Jain G, et al. Innate immune memory in the brain shapes neurological disease hallmarks. Nature. 2018 Apr;556(7701):332–8.

Metabolism

The impact of biological sex on mitochondrial metabolism in cardiomyocytes

Laboratory name: Laboratory of Cardiometabolism

Supervisor (email): Lukas Chmatal, Ph.D. (Lukas.chmatal@fgu.cas.cz)

Laboratory website: https://fgu.cas.cz/en/research-and-laboratories/research-departments/laboratory-of-cardiometabolism/, https://www.chmatallab.com/

PhD project: The impact of biological sex on mitochondrial metabolism in cardiomyocytes

Heart disease is the leading cause of death worldwide, with marked differences in symptoms, prevalence, and outcomes between sexes. Understanding the molecular mechanisms underlying these sex differences is key for addressing the unique needs of male and female patients. My lab has a deep interest in metabolic sex differences and their role in human health and disease. Our previous research showed that human heart metabolism differs between healthy males and females. Specifically, we showed that mitochondrial fatty acid oxidation – the main source of heart’s energy – is more potent in female cardiac cells compared to males. We thus ask a key biological question: How does biological sex influence overall mitochondrial metabolism and function in heart cells? Using state-of-the-art metabolomics, proteomics, and fluorescence microscopy in genetically engineered mouse models with fluorescently tagged cardiac mitochondria, we study how biological sex – a unique combination of sex chromosomes and sex hormones – shapes mitochondrial function. We’re looking for a passionate, curious, and collaborative individuals to join our emerging team. If you’re interested in mitochondrial biology, metabolism, and sex differences, we’d love to hear from you!

Candidate’s profile (requirements):

You hold a Master’s degree in biological, medical, chemical, or biochemical sciences, or you are on track to complete your studies this academic year. You are a motivated, detail-oriented individual with experience in cell biology, molecular biology, or metabolomics, and you are comfortable working with both mouse and human samples. You are fluent in English and have excellent communication skills and enjoy creating and working in an inclusive, supportive and collaborative team driven by a shared goal.

References:

Maya Talukdar*, Lukas Chmátal*, Linyong Mao, Daniel Reichart, Danielle Murashige, Yelena Skaletsky, Daniel M. DeLaughter, Zoltan Arany, Jonathan G. Seidman, Christine Seidman, David C. Page. Genes of fatty acid oxidation pathway are upregulated in the female as compared to male human cardiomyocytes. Circulation (2025), *co-first authors
Daniel Reichart, Gregory A. Newby, Hiroko Wakimoto, Mingyue Lun, Joshua M. Gorham, Justin J. Curran, Aditya, Raguram, Daniel M. DeLaughter, David A. Conner, Júlia D. C. Marsiglia1, Sajeev Kohli, Lukas Chmátal, David C. Page, Nerea Zabaleta, Luk Vandenberghe, David R. Liu, Jonathan G. Seidman, and Christine Seidman. Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice. Nature Medicine, 29: 412-421 (2023)
Akera T., Chmátal L., Trimm E., Yang K., Aonbangkhen C., Chenoweth D.M., Janke C., Schultz R.M., Lampson M.A. Spindle asymmetry drives non-Mendelian chromosome segregation. Science, 358(6363): 668-672 (2017)

The impact of the inactive X chromosome on metabolic differences between male and female tissues throughout the body

Laboratory name: Laboratory of Cardiometabolism

Supervisor (email): Lukas Chmatal, Ph.D. (Lukas.chmatal@fgu.cas.cz)

Laboratory website: https://fgu.cas.cz/en/research-and-laboratories/research-departments/laboratory-of-cardiometabolism/, https://www.chmatallab.com/

PhD project: The impact of the inactive X chromosome on metabolic differences between male and female tissues throughout the body

Numerous human diseases exhibit significant differences in symptoms, prevalence, and outcomes between males and females. For example, cardiovascular diseases and autism spectrum disorder are more common in men, whereas autoimmune diseases and Alzheimer’s disease are more common in women. Since many of the sex-biased disorders have associated metabolic phenotype, my lab is first interested in characterizing what metabolites and metabolic pathways are different between male and female mouse tissues and, second, in characterizing molecular mechanisms of these sex differences with a special focus on inactive X chromosome and its genes. To uncouple the potential effects of Xi from those of the Y chromosome and circulating sex hormones, I will conduct multi-tissue metabolomic profiling using the XY* mouse model. These mice contain an abnormal Y chromosome (Y*) derived from the LT/Sv strain, where it originated through a spontaneous fusion between the X and Y chromosomes. In XY* males, meiotic recombination produces four types of sperm, which, after crossing with XX females, result in four types of offspring: XO females, XX females, XY* males, and XXY* males. One Xi is present in both XX females and XXY* males, allowing for tissue metabolite comparisons between X_aO females and X_aX_i females, or between X_aY* males and X_aX_iY* males. These analyses will isolate the impact of Xi from effects of the sex hormonal milieu, which remains identical within each comparison. This approach will offer a more holistic view of Xi’s contribution to sex differences in metabolism across various tissues, identifying Xi-driven metabolites and pathways that are either shared or tissue-specific. In a pilot metabolomic study we will include samples from different developmental stages (pre-pubertal, young adult, old) to understand the interaction between Xi impact on metabolism and aging. I anticipate that these studies will establish the Xi chromosome as a fundamental molecular driver of metabolic differences between male and female tissues.

Candidate’s profile (requirements):

References:

Maya Talukdar*, Lukas Chmátal*, Linyong Mao, Daniel Reichart, Danielle Murashige, Yelena Skaletsky, Daniel M. DeLaughter, Zoltan Arany, Jonathan G. Seidman, Christine Seidman, David C. Page. Genes of fatty acid oxidation pathway are upregulated in the female as compared to male human cardiomyocytes. Circulation (2025), *co-first authors
Daniel Reichart, Gregory A. Newby, Hiroko Wakimoto, Mingyue Lun, Joshua M. Gorham, Justin J. Curran, Aditya, Raguram, Daniel M. DeLaughter, David A. Conner, Júlia D. C. Marsiglia1, Sajeev Kohli, Lukas Chmátal, David C. Page, Nerea Zabaleta, Luk Vandenberghe, David R. Liu, Jonathan G. Seidman, and Christine Seidman. Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice. Nature Medicine, 29: 412-421 (2023)
Akera T., Chmátal L., Trimm E., Yang K., Aonbangkhen C., Chenoweth D.M., Janke C., Schultz R.M., Lampson M.A. Spindle asymmetry drives non-Mendelian chromosome segregation. Science, 358(6363): 668-672 (2017)

Studying the role of antioxidant dipeptides in stem cell metabolism

Laboratory: Laboratory of Molecular Physiology of Bone

Supervisor: Michaela Tencerova, Ph.D. (Michaela.Tencerova@fgu.cas.cz)

Website: https://fgu.cas.cz/vyzkum-a-laboratore/vyzkumna-oddeleni/molekularni-fyziologie-kosti/

PhD project: Studying the role of antioxidant dipeptides in stem cell metabolism

Bone fragility is a critical yet overlooked complication of metabolic diseases, often associated with increased accumulation of bone marrow adipose tissue (BMAT). We uncover BMAT as a unique fat depot that retains insulin sensitivity in obesity compared to peripheral adipose tissue (AT), challenging conventional fat-bone interactions. Our metabolomic profiling identifies a novel dipeptide signaling pathway that affects bone marrow stromal cells (BMSCs) under metabolic stress. We reveal elevated dipeptides and Slc15a transporters in BM under obesogenic conditions, establishing the first mechanistic link between dipeptide transport and bone homeostasis. Thus, this project will investigate how Slc15a-mediated signaling reprograms stem cell fate at the bone-fat interface, with a focus on sex-specific regulation, an overlooked aspect. Our findings may provide new insights into obesity-induced bone fragility and lead to the development of novel therapeutic approaches for prevention of bone fragility and early onset of osteoporosis.

The project will employ in vitro cell work using murine and human BMSCs in treatment with antioxidant dipeptides, animal work (diet intervention in mouse models of obesity) and in vivo phenotyping techniques (analyzing glucose and insulin metabolism, bone microstructure using different bioimaging methods microCT, contrast-enhanced CT, and specific program analysis for bone and BMAT evaluation), isolation of primary BMSCs and applying several molecular, bioanalytical methods for measurement of cell metabolism (bioenergetics, nutrient uptake, protein and RNA analysis) and learning new techniques such as single cell sequencing and spatial transcriptomics. The PhD Program will be conducted at the Faculty of Science at the Charles University in Prague and the PhD work will be conducted at the Institute of Physiology of the Czech Academy of Sciences in Prague in collaboration with excellent laboratories abroad.

Candidate’s profile (requirements):

We are seeking highly motivated, creative candidates with M.Sc. degree or equivalent in molecular biology, biochemistry, physiology, medicine, pharmacology or related disciplines, or students expecting to obtain their degree this year. Experience with molecular biology techniques, and in vitro cell culture methods or animal work are advantage.

Relevant publications:

– Dzubanova M. et al., Glutamine: A novel player in maintaining skeletal strength and body fitness in obese mice. Clin Nutr. 2025 Nov;54:162-176. doi: 10.1016/j.clnu.2025.09.018. Epub 2025 Oct 9.

–Benova A., et al. Novel thiazolidinedione analog reduces a negative impact on bone and mesenchymal stem cell properties in obese mice compared to classical thiazolidinediones. Mol Metab. 2022 Nov;65:101598. doi: 10.1016/j.molmet.2022.101598. Epub 2022 Sep 11

-Tencerova M, et al. Metabolic programming of bone marrow stromal stem cells determines lineage- differentiation fate. Bone Res. 2019 Nov 14;7:35. doi: 10.1038/s41413-019-0076-5.

-Tencerova M, et al. Obesity associated hypermetabolism and accelerated senescence of bone marrow stromal stem cells suggest a potential mechanism for bone fragility. Cell Rep. 2019 May 14;27(7):2050-2062.e6. doi: 10.1016/j.celrep.2019.04.066.

-Tencerova M, et al. High fat diet-induced obesity promotes expansion of bone marrow adipose tissue and impairs skeletal stem cell functions in mice. J Bone Miner Res. 2018 Feb 14. doi: 10.1002/jbmr.3408.

Novel strategies to investigate the origins of metabolic dysfunction-associated steatohepatitis

Laboratory name: Laboratory of Adipose Tissue Biology

Supervisor (email): Martin Rossmeisl, MD, Ph.D. (Martin.Rossmeisl@fgu.cas.cz)

Laboratory website: https://fgu.cas.cz/en/research-and-laboratories/research-departments/laboratory-of-adipose-tissue-biology/

PhD project: Novel strategies to investigate the origins of metabolic dysfunction-associated steatohepatitis

Metabolic (dysfunction)-associated steatotic liver disease (MASLD) is a complex disorder whose pathogenesis involves (epi)genetic and metabolic factors. MASLD represents a spectrum of conditions ranging from increased intrahepatic accumulation of triacylglycerols (steatosis) to steatohepatitis (MASH) characterized by hepatocellular inflammation that can progress to fibrosis, cirrhosis and hepatocellular carcinoma. The mechanisms involved in the transition from benign steatosis to the more clinically severe stages of MASLD are not fully understood. Although MASLD is frequently associated with obesity and other cardiometabolic risk factors, it can also occur in lean patients, and lean patients with a progressive form of MASLD (i.e. MASH) exhibit an increased risk of mortality compared to their non-lean counterparts.

The aim of this PhD project is to identify the mechanisms that contribute primarily to the pathogenesis of MASLD/MASH in lean individuals. The selected PhD student will conduct dietary interventions in male and female mice, using various diets that promote the development of MASLD/MASH, differing in their ability to induce obesity and the degree of MASLD progression. The experiments will include in vivo phenotyping of lipid and glucose metabolism (e.g., tolerance tests, hyperinsulinemic-euglycemic clamps), ex vivo functional analyses in adipose tissue explants and in isolated hepatocytes, as well as biochemical, histological, molecular biology and metabolomics analyses.

Candidate’s profile (requirements):

We are seeking outstanding self-motivated candidates with master’s degree or equivalent in physiology, biochemistry, molecular biology, medicine or related fields, or those expecting to obtain their degree this year. Candidates should be able to work independently and speak English fluently. This position involves extensive work with laboratory animals (primarily mice). Experience with animal models and working with animals (laboratory mice or rats), in vivo phenotyping techniques, histological analysis, metabolomics, and biochemical/molecular biology techniques is an advantage.

References:

Horakova O, Sistilli G, Kalendova V, Bardova K, Mitrovic M, Cajka T, Irodenko I, Janovska P, Lackner K, Kopecky J, Rossmeisl M. 2023. Thermoneutral housing promotes hepatic steatosis in standard diet-fed C57BL/6N mice, with a less pronounced effect on NAFLD progression upon high-fat feeding. Frontiers in Endocrinology. 14:1205703.
Mitrovic M, Sistilli G, Horakova O, Rossmeisl M. 2022. Omega-3 phospholipids and obesity-associated NAFLD: Potential mechanisms and therapeutic perspectives. Eur J Clin Invest. 52(3):e13650.
Sistilli G, Kalendova V, Cajka T, Irodenko I, Bardova K, Oseeva M, Zacek P, Kroupova P, Horakova O, Leckner K, Gastaldelli A, Kuda O, Kopecky J, Rossmeisl M. 2021. Krill oil supplementation reduced exacerbated hepatic steatosis induced by thermoneutral housing in mice with diet-induced obesity. Nutrients. 13:437.
Paluchova V, Vik A, Cajka T, Brezinova M, Brejchova K, Bugajev V, Draberova L, Draber P, Buresova J, Kroupova P, Bardova K, Rossmeisl M, Kopecky J, Hansen TV, Kuda O. 2020. Triacylglycerol-rich oils of marine origin are optimal nutrients for induction of polyunsaturated docosahexaenoic acid ester of hydroxy linoleic acid (13-DHAHLA) with anti-inflammatory properties in mice. Molecular Nutrition Food Research. 64: 1901238.

Biochemical Regulation of Human Milk Composition in Gestational Diabetes

Laboratory name: Laboratory of Metabolism of Bioactive Lipids

Supervisor (email): Ondrej Kuda, Ph.D. (ondrej.kuda@fgu.cas.cz)

Laboratory website: https://fgu.cas.cz/en/research-and-laboratories/research-departments/laboratory-of-metabolism-of-bioactive-lipids/

PhD project: Biochemical Regulation of Human Milk Composition in Gestational Diabetes

This PhD project focuses on understanding how maternal metabolism and gestational diabetes mellitus (GDM) influence the biochemistry of human milk production. The student will study the physiological and metabolic mechanisms underlying lactation, with an emphasis on lipid synthesis, transport, and secretion in the mammary gland. Experimental work will involve comprehensive analysis of human milk samples using liquid and gas chromatography coupled with mass spectrometry (LC-MS and GC-MS) to characterize lipid and metabolite composition. Metabolic tracing with non-radioactive deuterated water (2H2O) will be used to assess de novo lipogenesis and identify tissue sources contributing to milk lipids. Comparative analyses of saliva will explore its potential as a non-invasive marker of maternal metabolic status. Through integration of biochemical data with clinical and physiological parameters, the project will reveal how metabolic control during pregnancy shapes milk composition and lactational function.

The work will be conducted at the IPHYS CAS. The work is financially secured in terms of material and full time position.

Candidate’s profile (requirements):

Field: Biochemistry + Pathobiochemistry / Physiology

The candidate should have interest in metabolism, endocrinology, and analytical biochemistry, with motivation for experimental work on human samples.

References:

Brejchova et al. Triacylglycerols containing branched palmitic acid ester of hydroxystearic acid (PAHSA) are present in the breast milk and hydrolyzed by carboxyl ester lipase. Food Chem. 2022 Sep 15;388:132983. doi: 10.1016/j.foodchem.2022.132983.
Brejchova et al. Distinct roles of adipose triglyceride lipase and hormone-sensitive lipase in the catabolism of triacylglycerol estolides. Proc Natl Acad Sci U S A. 2021 Jan 12;118(2):e2020999118. doi: 10.1073/pnas.2020999118
Brezinova et al. Levels of palmitic acid ester of hydroxystearic acid (PAHSA) are reduced in the breast milk of obese mothers. Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Feb;1863(2):126-131. doi: 10.1016/j.bbalip.2017.11.004

Deciphering Lipid Metabolism in Cancer: Integrative Approaches in Metabolomics, Fluxomics, and Metabolic Engineering

Laboratory name: Laboratory of Metabolism of Bioactive Lipids

Supervisor (email): Ondrej Kuda, Ph.D. (ondrej.kuda@fgu.cas.cz)

Laboratory website: https://fgu.cas.cz/en/research-and-laboratories/research-departments/laboratory-of-metabolism-of-bioactive-lipids/

PhD project: Deciphering Lipid Metabolism in Cancer: Integrative Approaches in Metabolomics, Fluxomics, and Metabolic Engineering

This PhD project investigates the rewiring of lipid metabolic pathways in cancer using an integrative approach combining metabolomics, fluxomics, metabolic engineering, and in silico modeling. The research aims to deconvolute complex lipid metabolic pathways through metabolic flux analysis and stable isotope tracer studies, supported by Python-based data processing pipelines and advanced computational modeling.

The study incorporates experimental work, including cancer cell culture systems and in vivo mouse models, to validate findings and quantify metabolic fluxes under physiological and pathological conditions. In silico simulations of lipid metabolism will be used to predict pathway behavior and identify potential intervention points. Machine learning approaches will aid in biomarker discovery and the prediction of metabolic vulnerabilities, offering insights into the mechanisms driving cancer progression and potential therapeutic targets.

This interdisciplinary project bridges computational biology, biochemistry, and experimental cancer research, contributing to our understanding of lipid metabolism and the development of precision strategies for metabolic engineering and cancer therapy.

The work will be conducted at the IPHYS CAS. The work is financially secured in terms of material and full time position.

Candidate’s profile (requirements):

Field: Physiology / Bioinformatics

The prerequisites for success are basic knowledge of programming languages for working with data (Python), basic biochemistry (metabolites, pathways, cellular compartments), and an overview of omics disciplines. Previous experience with cell cultures and mouse experiments is an advantage.

References:

Morigny et al. Multi-omics profiling of cachexia-target tissues reveals a spatio-temporal coordinated response to cancer. Nature Metabolism, 2026. doi: 10.1038/s42255-025-01434-3
Brejchova et al. Uncovering mechanisms of thiazolidinediones on osteogenesis and adipogenesis using spatial fluxomics. Metabolism. 2025 May:166:156157. doi: 10.1016/j.metabol.2025.156157
Vondrackova et al. LORA, Lipid Over-Representation Analysis Based on Structural Information. Anal Chem. 2023 Aug 29;95(34):12600-12604. doi: 10.1021/acs.analchem.3c02039
https://github.com/IPHYS-Bioinformatics

Comprehensive Metabolome and Lipidome Characterization Using Integrated Analytical Platforms

Laboratory name: Laboratory of Translational Metabolism

Supervisor (email): Assoc. Prof. Tomas Cajka, Ph.D. (tomas.cajka@fgu.cas.cz)

Laboratory website: https://fgu.cas.cz/en/research-and-laboratories/research-departments/laboratory-of-translational-metabolism/

PhD project: Comprehensive Metabolome and Lipidome Characterization Using Integrated Analytical Platforms

Over the last decade, mass spectrometry-based metabolomics and lipidomics have become central platforms for the comprehensive profiling of polar metabolites, volatile and semi-volatile compounds, and complex lipids in biological samples, including plasma, serum, urine, and tissues. The combination of chromatographic separation techniques with mass spectrometry, particularly liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS), enables complementary coverage of chemically diverse metabolite and lipid classes and remains essential for high-confidence metabolome and lipidome characterization. Despite major methodological advances, comprehensive and systematically organized metabolomic and lipidomic datasets from biofluids and tissues that are readily accessible and reusable across studies remain limited. This Ph.D. project aims to develop and apply integrated LC-MS- and GC-MS-based strategies for comprehensive characterization of the metabolome and lipidome in biological samples. The project will focus on (i) combining targeted and untargeted analytical workflows, (ii) expanding and curating mass spectral libraries to improve metabolite and lipid annotation, and (iii) applying bioinformatics and visualization tools for robust interpretation of metabolomics and lipidomics data in experimental and clinical contexts. The work will be conducted at the Institute of Physiology of the Czech Academy of Sciences and financially supported by grants from the Ministry of Education, Youth and Sports (MŠMT), the Czech Health Research Council (AZV), and the European Union’s Horizon Europe program. The PhD program will be conducted at the Faculty of Science at the Charles University in Prague and the dissertation work will be conducted at the Institute of Physiology of the Czech Academy of Sciences in Prague.

Candidate’s profile (requirements):

We are seeking outstanding, self-motivated candidates with a master’s degree (or equivalent) in analytical chemistry, biochemistry, or a related field, or candidates who are expected to obtain their degree by the end of the current academic year. Applicants should be fluent in English. Experience with LC-MS or GC-MS, as well as with the processing and analysis of metabolomics and lipidomics datasets, is an advantage.

References:

T. Cajka, J. Hricko, L. Rudl Kulhavá, M. Paucova, M. Novakova, V. Hola, S. Rakusanova, O. Fiehn, V. Skop, I. Lankova, I. Miskova, T. Pelikanova, M. Haluzík: Untargeted metabolomics identifies N-lactoyl-amino acids as dose-responsive plasma biomarkers of metformin adherence in type 2 diabetes. Clinical Pharmacology & Therapeutics (2026) in press. (doi: 10.1002/cpt.70205)
L. Rudl Kulhava, P. Houdek, M. Novakova, J. Hricko, M. Paucova, O. Kuda, M. Sladek, O. Fiehn, A. Sumova, T. Cajka: Circadian Ontogenetic Metabolomics Atlas: An interactive resource with insights from rat plasma, tissues, and feces. Cellular and Molecular Life Sciences 82 (2025) 264. (doi: 10.1007/s00018-025-05783-w)
S. Rakusanova, T. Cajka: Tips and tricks for LC–MS-based metabolomics and lipidomics analysis. TrAC Trends in Analytical Chemistry 180 (2024) 117940. (doi: 10.1016/j.trac.2024.117940)
H. Tsugawa, K. Ikeda, M. Takahashi, A. Satoh, Y. Mori, H. Uchino, N. Okahashi, Y. Yamada, I. Tada, P. Bonini, Y. Higashi, Y. Okazaki, Z. Zhou, Z.-J. Zhu, J. Koelmel, T. Cajka, O. Fiehn, K. Saito, M. Arita, M. Arita: A lipidome atlas in MS-DIAL 4. Nature Biotechnology 38 (2020) 1159–1163. (doi: 10.1038/s41587-020-0531-2)

Impact of gestational diabetes management strategies on breast milk composition and early neonatal metabolic health

Laboratory name: Laboratory of Metabolism of Bioactive Lipids

Supervisor (email): Kristyna Brejchova, Ph.D. (Kristyna.Brejchova@fgu.cas.cz)

Laboratory website: https://fgu.cas.cz/en/research-and-laboratories/research-departments/laboratory-of-metabolism-of-bioactive-lipids/

PhD project: Impact of gestational diabetes management strategies on breast milk composition and early neonatal metabolic health

In this PhD project, you will investigate the impact of two therapeutic strategies for gestational diabetes mellitus (GDM) on changes in the biochemical profile of human breast milk and their effect on the healthy development and growth of newborns. The study compares the effects of a standardized dietary regimen and pharmacological antidiabetic therapy on the lipid profile of breast milk in the context of the mother’s metabolic status and healthy infant growth.

The diagnosis of GDM will be established by a standard oral glucose tolerance test (OGTT) at 24–28 weeks of gestation, and maternal medical history, changes in body weight during pregnancy and blood glucose levels will be closely monitored, with glycaemia assessed by continuous glucose monitoring. In parallel, fetal biometry will be performed to evaluate intrauterine growth. During lactation, samples of colostrum, transitional and mature breast milk will be collected from all women, complemented by saliva samples as a non‑invasive indicator of maternal metabolic status. Mothers will be divided into three groups: healthy controls with normal glycaemia, women with GDM treated only with a standardized dietary regimen, and women with GDM requiring pharmacological antidiabetic treatment. The research work includes analysis of biological samples using liquid and gas chromatography coupled to mass spectrometry (LC‑MS and GC‑MS), followed by statistical evaluation of the data. In parallel, infant parameters (body weight, growth) will be monitored at defined time points to assess the relationships between maternal glycaemia, breast milk composition, salivary metabolome and early growth and nutritional status of the child.

The findings obtained will help optimize care for mothers with GDM to ensure optimal nutritional quality of breast milk and support a healthy start to life for their newborns.

Candidate’s profile (requirements):

Field of Study: Biochemistry/ Physiology

The candidate should have an interest in metabolism, endocrinology, and biochemistry, along with a motivation for experimental work with human samples.

References:

Brejchova et al. Triacylglycerols containing branched palmitic acid ester of hydroxystearic acid (PAHSA) are present in the breast milk and hydrolyzed by carboxyl ester lipase. Food Chem. 2022 Sep 15;388:132983. doi: 10.1016/j.foodchem.2022.132983.
Brejchova et al. Uncovering mechanisms of thiazolidinediones on osteogenesis and adipogenesis using spatial fluxomics. Metabolism. 2025 May;166:156157. doi: 10.1016/j.metabol.2025.156157. Epub 2025 Feb 11.PMID: 39947516.
Brejchova et al. Distinct roles of adipose triglyceride lipase and hormone-sensitive lipase in the catabolism of triacylglycerol estolides. Proc Natl Acad Sci U S A. 2021 Jan 12;118(2):e2020999118. doi: 10.1073/pnas.2020999118
Brezinova et al. Levels of palmitic acid ester of hydroxystearic acid (PAHSA) are reduced in the breast milk of obese mothers. Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Feb;1863(2):126-131. doi: 10.1016/j.bbalip.2017.11.004

The PhD program will be conducted at the Faculty of Science at the Charles University in Prague and the dissertation work will be conducted at the Institute of Physiology of the Czech Academy of Sciences in Prague.

Mesenteric adipose tissue as part of the intestinal barrier in the progression of MASLD

Laboratory name: Laboratory of Adipose Tissue Biology

Supervisor (email): Olga Horáková, PhD. (olga.horakova@fgu.cas.cz)

Laboratory website

PhD project: Mesenteric adipose tissue as part of the intestinal barrier in the progression of MASLD

The pathophysiology of metabolic steatotic liver disease (MASLD) includes obesity with excessive accumulation of hepatic fat and, in later stages, metabolic dysfunction of hepatocytes, inflammation and fibrosis with subsequent risk of hepatocellular carcinoma. The progression of MASLD is also stimulated by the external environment, not only by dangerous pathogens, but also by essentially harmless molecules such as food-derived antigens. The well-known protection of the liver from the outside world is provided by the multi-layered intestinal barrier. We hypothesize that mesenteric adipose tissue (mWAT) is an integral part of this barrier.

The aims of this project are 1) to define the role of mWAT in small intestinal barrier function during the development of MASLD and 2) to explore the potential of omega-3 fatty acids (primarily phospholipids) to improve ileal barrier function. We will use a mouse model of diet-induced MASLD (including germ-free mice), functional analysis of adipose and intestinal tissue, flow cytometry, metabolipidomic analysis, and bioinformatics. Understanding the role of mWAT in the progression of MASLD will help to develop new treatments.

Candidate’s profile (requirements):

We are looking for highly motivated PhD student with an MSc. degree or equivalent in life sciences or related fields, or those who expect to graduate this year. Previous experience with animal experiments, flow cytometry or bioinformatics is an advantage.

References:

Horáková, Olga – Kroupová, Petra – Bardová, Kristina – Burešová, Jana – Janovská, Petra – Kopecký, Jan – Rossmeisl, Martin Metformin acutely lowers blood glucose levels by inhibition of intestinal glucose transport. Scientific Reports 2019, 9(Apr 16)), 6156. doi: 10.1038/s41598-019-42531-0

Kroupová; Petra – van Schothorst; E. M. – Keijer; J. – Bunschoten; A. – Vodička; Martin – Irodenko; Ilaria – Oseeva; Marina – Žáček; P. – Kopecký; Jan – Rossmeisl; Martin – Horáková; Olga Omega-3 Phospholipids from Krill Oil Enhance Intestinal Fatty Acid Oxidation More Effectively than Omega-3 Triacylglycerols in High-Fat Diet-Fed Obese Mice. Nutrients. 2020; 12(7)); 2037. doi: 10.3390/nu12072037

Mitrović; Marko – Sistilli; Gabriella – Horáková; Olga – Rossmeisl; Martin Omega-3 phospholipids and obesity-associated NAFLD: Potential mechanisms and therapeutic perspectives. European Journal of Clinical Investigation. 2022; 52(3)); e13650. doi: 10.1111/eci.13650

The role of mitochondrial phospholipase A2γ and mitochondrial redox and lipid signaling in selected tissues

Laboratory name: Mitochondrial Physiology

Supervisor (email): Martin Jabůrek, Ph.D. (martin.jaburek@fgu.cas.cz)

Laboratory website

PhD project: The role of mitochondrial phospholipase A2γ and mitochondrial redox and lipid signaling in selected tissues

Mitochondria are dynamic, energy-transforming, and signaling organelles that have become the most studied organelle in the biomedical sciences. One of the long-term goals of our laboratory includes uncovering mechanisms in which mitochondrial oxidants, lipids, and lipid-derived electrophiles participate in redox homeostasis and cellular signaling. This includes the convergence of mitochondrial lipid and redox signaling and the role of mitochondrial phospholipases.

The aim of the PhD project is to characterize the role of mitochondrial phospholipase A2γ and mitochondria-derived lipids in selected tissues and cell types. Our current focus is on brown adipocytes, specialized in non-shivering thermogenesis, and pancreatic β-cells, responsible for insulin secretion, but this project can involve other tissues and cell types. Our laboratory uses a wide range of biochemical and biophysical approaches, including models of isolated reconstituted iPLA2y, isolated mitochondria, isolated brown adipocytes and pancreatic islets, and in vivo models using genetically modified mice. There are plenty of opportunities for motivated students.

Candidate’s profile (requirements):

We are seeking outstanding self-motivated candidates with bachelor’s degree or master’s degree in biochemistry, physiology, molecular biology, or related fields, or those expecting to obtain their degree within the year. Candidates should be fluent in English. Experience with biochemical and molecular biology techniques is an advantage.

References:

Jabůrek M., et al. (2024) Mitochondria to plasma membrane redox signaling is essential for fatty acid β-oxidation-driven insulin secretion. Redox Biol. 75:103283

Ježek P., et al. (2024) Mitochondrial Physiology of Cellular Redox Regulations. Physiol Res. 73(S1): S217-S242

Průchová P., et al. (2022) Antioxidant role and cardiolipin remodeling by redox-activated mitochondrial Ca²⁺-independent phospholipase A2γ in the brain. Antioxidants 11(2):198

Effect of genetic factors and perinatal programming on individual mechanisms of non-shivering thermogenesis in mice

Laboratory name: Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences

Laboratory website

Supervisor: Ing. Petra Janovska, PhD (petra.janovska @fgu.cas.cz; ORCID 0000-0002-6154-2175)

PhD project: Effect of genetic factors and perinatal programming on individual mechanisms of non-shivering thermogenesis in mice

Our recent results obtained in mice suggested a possibility to reduce obesity through adaptive enhancement of non-shivering thermogenesis (NST) in skeletal muscle. This PhD project focuses on the characterization of the: (i) role of genetic background of mice on muscle NST and its subsequent effect on obesity; (ii) mechanisms responsible for the permanent setting of muscle NST levels during a critical time window shortly after birth, as indicated by our unpublished results; and (iii) in vitro effects of candidate compounds on energy expenditure in muscle satellite cells derived from mice differing in capacity for muscle NST. The project will employ: (i) long-term experiments in mice with in vivo phenotyping of whole-body metabolism; (ii) utilization of omics techniques and associated data analyses; and (iii) application of bioanalytical methods in vitro. This research will deepen understanding of muscle NST and its potential as a novel therapeutic target for obesity treatment. By exploring the genetic and developmental factors influencing NST, as well as testing effects of selected compounds in muscle cells, this project may pave the way for innovative obesity interventions.

Candidate’s profile (requirements):

We are seeking highly motivated, creative candidates with Master degree or equivalent in molecular biology, biochemistry, physiology, medicine, pharmacology or related disciplines, or students expecting to obtain their degree this year. Experience with bioinformatics or application of basic statistical methods in biology are advantage.

Relevant publications:

Janovska P, Zouhar P, Bardova K, Otahal J, Vrbacky M, Mracek T, Adamcova K, Lenkova L, Funda J, Cajka T, Drahota Z, Stanic S, Rustan A.C, Horakova O, Houstek J, Rossmeisl M and Kopecky J. 2023 Impairment of adrenergically-regulated thermogenesis in brown fat of obesity-resistant mice is compensated by non-shivering thermogenesis in skeletal muscle. Molecular Metabolism 69: 101683.

https://doi.org/10.1016/j.molmet.2023.101683

Bardova K, Janovska P, Vavrova A, Kopecký J, Zouhar P. 2024 Adaptive induction of nonshivering thermogenesis in muscle rather than brown fat could counteract obesity. Physiological Research 73:S279-S294 https://doi.org/10.33549/physiolres.935361

Deciphering Lipid Metabolism in Cancer: Integrative Approaches in Metabolomics, Fluxomics, and Metabolic Engineering

Laboratory name: Metabolism of Bioactive Lipids

Supervisor (email): Ondrej Kuda (ondrej.kuda@fgu.cas.cz)

Laboratory website

PhD project: Deciphering Lipid Metabolism in Cancer: Integrative Approaches in Metabolomics, Fluxomics, and Metabolic Engineering

The study incorporates experimental work, including cancer cell culture models and in vivo mouse models, to validate findings and quantify metabolic fluxes under physiological and pathological conditions. In silico simulations of lipid metabolism will be used to predict pathway behavior and identify potential intervention points. Machine learning approaches will aid in biomarker discovery and the prediction of metabolic vulnerabilities, offering insights into the mechanisms driving cancer progression and potential therapeutic targets.

The work will be conducted at the IPHYS CAS. The work is financially secured in terms of material and full time position.

Candidate’s profile (requirements):

The prerequisites for success are knowledge of programming languages for working with data (Python), basic biochemistry (metabolites, pathways, cellular compartments), and an overview of omics disciplines. Previous experience with cell cultures and mouse experiments is an advantage.

References:

Lopes et al. Metabolomics atlas of oral 13C-glucose tolerance test in mice. Cell Rep. 2021 Oct 12;37(2):109833. doi: 10.1016/j.celrep.2021.109833

Vondrackova et al. LORA, Lipid Over-Representation Analysis Based on Structural Information. Anal Chem. 2023 Aug 29;95(34):12600-12604. doi: 10.1021/acs.analchem.3c02039

https://github.com/IPHYS-Bioinformatics

Integrated approaches for metabolomics and lipidomics - data-driven insight using machine learning and biochemical networks

Laboratory name: Metabolism of Bioactive Lipids

Supervisor (email): Ondrej Kuda (ondrej.kuda@fgu.cas.cz)

Laboratory website

PhD project: Integrated approaches for metabolomics and lipidomics – data-driven insight using machine learning and biochemical networks

This PhD project focuses on advancing the integration of metabolomics and lipidomics to unravel the regulation of complex biochemical networks and metabolic dynamics. The study leverages state-of-the-art data processing techniques, computational tools, and machine learning algorithms to extract actionable insights from large-scale fluxomics datasets. Python-based pipelines will be developed to standardize data preprocessing, feature extraction, and analysis while incorporating machine learning models for network clustering, classification, and predictive modeling of metabolic pathways.

The project emphasizes cross-disciplinary approaches, blending expertise in biochemistry, computational biology, and data science to create robust tools for understanding metabolic systems. Outcomes are expected to contribute to personalized medicine, metabolic engineering, and systems biology, offering novel methodologies and software frameworks for the scientific community.

The work will be conducted at the IPHYS CAS, where the metabolomics and proteomics service laboratory is located. The work is financially secured in terms of material and full time position.

Candidate’s profile (requirements):

The prerequisites for success are knowledge of programming languages for working with data (Python), basic biochemistry (metabolites, pathways, cellular compartments), and an overview of omics disciplines. The candidate should be fluent in English and willing to travel to collaborating laboratories abroad.

References:

Lopes et al. Metabolomics atlas of oral 13C-glucose tolerance test in mice. Cell Rep. 2021 Oct 12;37(2):109833. doi: 10.1016/j.celrep.2021.109833

Vondrackova et al. LORA, Lipid Over-Representation Analysis Based on Structural Information. Anal Chem. 2023 Aug 29;95(34):12600-12604. doi: 10.1021/acs.analchem.3c02039

https://github.com/IPHYS-Bioinformatics

Studies of mitochondrial lipotoxic dysfunction in pancreatic cancer

Laboratory name: Mitochondrial Physiology

Supervisor (email): Katarína Smolková (katarina.smolkova@fgu.cas.cz)

Laboratory website

PhD project: Studies of mitochondrial lipotoxic dysfunction in pancreatic cancer

Inhibition of mitochondrial metabolism in non-adipose tissues results in triglyceride (TG) synthesis and accumulation in lipid droplets (LDs). This is caused by inhibited import of activated fatty acids (FAs) into mitochondria, which leads to redirection of FAs into LDs and protects from the deleterious effects of FA oxidation (Gotvaldová et al 2024, PMID: 38532464). We aim to investigate mechanisms that regulate the utilization of FAs in mitochondria as opposed to TG synthesis and how this is reflected in mitochondrial lipotoxicity.

We will use cell knockout cell lines partially defective in TG synthesis, and also knockout of the mitochondrial enzyme CRAT, which is able to induce pancreatic tumorigenesis via epigenetic regulations. In this project, we aim to identify a lipotoxic culprit responsible for mitochondrial damage that affects mitochondrial function and cell survival. Using multi-omics approaches, we will identify metabolic and gene signatures associated with mitochondrial oxidative and lipotoxic damage. We will also focus on post-translational modifications in knockout models.

The goal of the project is to identify crosstalk mechanisms between cellular compartments, namely mitochondria, peroxisomes and LDs, focusing on FA dynamics within them. Our work should link the metabolic effects of mitochondrial oxidative processes to anabolic metabolism and reveal additional mechanisms of metabolic signaling in cancer cells.

Candidate’s profile (requirements):

(brief description of the required background of the applicants, i.e. education, title, languages, etc.)

We request a candidate with the experience in cell/molecular biology or biochemistry. Bacground in cancer biology is preferred, but not required.

References:

BCAA metabolism in pancreatic cancer affects lipid balance by regulating fatty acid import into mitochondria. Gotvaldová K, Špačková J, Novotný J, Baslarová K, Ježek P, Rossmeislová L, Gojda J, Smolková K Cancer & Metabolism 2024; 12, 10.

Pancreatic cancer: branched-chain amino acids as putative key metabolic regulators? Rossmeislová L, Gojda J, Smolková K. Cancer & Metastasis Reviews 2021; 40, 1115–1139.

Studying the role of bone marrow adipocytes in mouse models of obesity: impact of sex

Laboratory: Molecular Physiology of Bone

Supervisor (email): Michaela Tencerová, Ph.D. (michaela.tencerova@fgu.cas.cz)

Laboratory website

PhD project: Studying the role of bone marrow adipocytes in mouse models of obesity: impact of sex dimorphism

Obesity is a worldwide health problem associated with increased risk of fractures and bone damage, which are accompanied by higher bone marrow adipose tissue (BMAT) accumulation. With obesity, the function of key building blocks, bone marrow stromal cells (BMSCs), changes towards higher BMAT accumulation, which is influenced by diet and sexual dimorphism. Men and women have unique nutritional needs based on physiological and hormonal changes over the lifespan, which may contribute to the impact on the primary function of BMSCs and thus the prevalence of bone fractures in men and women. However, the precise molecular mechanism underlying sex-specific differences in the molecular properties of BMSCs and the pathophysiology of bone loss is not well understood. The aim of this project is to investigate the effect of different dietary interventions (e.g. different fatty acid, amino acid content) on BMAT expansion and molecular properties of BMSCs in mouse models with different susceptibility to obesity (obesity-prone C57BL/6 mice and obesity-resistant A/J mice). The study will also investigate how these factors affect bone quality, cellular metabolism of BMSCs with a particular focus on sexual dimorphism.

The project will employ mouse phenotyping methods (analyzing of metabolic parameters- i.e. glucose tolerance, body composition measured by DEXA, bone microstructure using different bioimaging methods microCT, contrast-enhanced CT, BMAT evaluation), isolation of primary BMSCs and applying several molecular methods (gene expression, protein analysis, differentiation capacity, bioenergetics etc.). Project will be conducted at the Institute of Physiology of CAS in collaboration with excellent laboratories abroad. The basic PhD scholarship will be supported by the national and international grants.

Candidate’s profile (requirements):

We are seeking highly motivated, creative candidates with MSc degree or equivalent in molecular biology, biochemistry, physiology, medicine, pharmacology or related disciplines, or students expecting to obtain their degree this year. Experience with molecular biology techniques and in vitro cell culture methods are advantage.

References:

Benova A., et al. Novel thiazolidinedione analog reduces a negative impact on bone and mesenchymal stem cell properties in obese mice compared to classical thiazolidinediones. Mol Metab. 2022 Nov;65:101598. doi: 10.1016/j.molmet.2022.101598. Epub 2022 Sep 11

Tencerova M, et al. Metabolic programming of bone marrow stromal stem cells determines lineage- differentiation fate. Bone Res. 2019 Nov 14;7:35. doi: 10.1038/s41413-019-0076-5.

Tencerova M, et al. Obesity associated hypermetabolism and accelerated senescence of bone marrow stromal stem cells suggest a potential mechanism for bone fragility. Cell Rep. 2019 May 14;27(7):2050-2062.e6. doi: 10.1016/j.celrep.2019.04.066.

Tencerova M, et al. High fat diet-induced obesity promotes expansion of bone marrow adipose tissue and impairs skeletal stem cell functions in mice. J Bone Miner Res. 2018 Feb 14. doi: 10.1002/jbmr.3408.

Tencerova M, Kassem M. The Bone Marrow-Derived Stromal Cells: Co mitment and Regulation of Adipogenesis. Front Endocrinol (Lausanne). 2016 Sep 21;7:127.

Role of efficiency of muscle contraction and non-shivering thermogenesis in protection against cold and obesity

Laboratory name: Adipose Tissue Biology

Laboratory website

Supervisor: Petr Zouhar, PhD (petr.zouhar@fgu.cas.cz; ORCID 0000-0002-1111-9109)

PhD project: Role of efficiency of muscle contraction and non-shivering thermogenesis in protection against cold and obesity

The excess of energy intake over energy expenditure leads to the development of obesity and its associated health complications. Important components of energy expenditure are the thermogenic mechanisms primarily designed to maintain a stable body temperature, but possibly also useful in ensuring energy homeostasis. In addition to brown adipose tissue, shivering and possible non-shivering mechanisms in skeletal muscle contribute significantly to thermogenesis. Our research to date has revealed significant variability in the extent of utilization of each mechanism among different inbred strains of laboratory mice, and possible link between higher involvement of muscle non-shivering thermogenesis and resistance to obesity.

As part of the PhD project, the student will test the hypothesis that non-shivering thermogenesis in skeletal muscle is facilitated by 1) the formation of respiratory chain supercomplexes, which influence the efficiency of ATP generation, and 2) the expression of the peptide sarcolipin, which regulates calcium transport across the sarcoplasmic reticulum membrane. This will be done by phenotyping genetically modified mouse strains with increased formation of respiratory supercomplexes, with particular emphasis on their susceptibility to obesity and on muscle contraction efficiency assessed by ex vivo measurements of contraction force, and energy expenditure during exercise and cold exposure assessed by indirect calorimetry.

Candidate’s profile (requirements):

We are seeking highly motivated, creative candidates with MSc degree or equivalent in molecular biology, biochemistry, physiology, medicine, pharmacology or related disciplines, or students expecting to obtain their degree this year. Experience with animal experiments, cell cultures, bioinformatics, and/or biostatistics are considered an advantage.

References:

https://doi.org/10.1016/j.molmet.2023.101683

In vivo and in vitro characterization of mechanisms of muscle non-shivering thermogenesis

Laboratory name: Adipose Tissue Biology

Supervisor (email): Mgr. Kristina Bardová, Ph.D. (kristina.bardova@fgu.cas.cz)

Laboratory website

PhD project: In vivo and in vitro characterization of mechanisms of muscle non-shivering thermogenesis

Energy homeostasis reflects a balance between energy intake and energy expenditure. In birds and mammals, control of energy expenditure is important for stable body temperature, and in all the organisms for regulation of body weight. Thus, energy expenditure represents a target for the prevention and treatment of obesity and associated diseases, which is a major problem for the health care systems in affluent societies.
The objective of this project is to explore in detail the mechanisms of muscle non-shivering thermogenesis, with a particular focus on calcium futile cycling facilitated by SERCA/sarcolipin interaction and respirátory supercomplex composition. Specifically, we will focus on (i) the role of sympathetic nervous system in the regulation of muscle non-shivering thermogenesis; (ii) in vitro model of pharmacological activation of futile calcium cycling in muscle cells; and (iii) the measurement of metabolism of isolated muscles and muscle fibres. The student will gain experience with the following methodology: immunohistochemistry and 3D evaluation, holotomographic microscope, indirect calorimetry, and high-resolution respirometry.
The student will be involved in the project under the supervision of Mgr. Kristina Bardova, Ph.D. In the first year of the program, student will be expected to acquire the necessary skills to complete the project. She will mainly focus on the introduction of methodology. Since the second year of the program, she will perform experiments on genetically modified models with manipulated muscle SERCA/sarcolipin system and respirátory supercomplex composition, both in vitro and in vivo. In the fourth year of the project, the results will be published in impacted journals.

Candidate’s profile (requirements):
Candidates must hold a Master of Science degree in a relevant discipline, such as biology, physiology, or a related field. Proficiency in either English or both English and Czech is essential, with the ability to communicate effectively in either English or in both languages.

References:
DOI: 10.1016/j.molmet.2023.101683
DOI: 10.33549/physiolres.935361

Cardiovascular Physiology

The effect of galectins and their inhibitors on vascular wall remodeling in pulmonary hypertension

Laboratory name: Laboratory of Biomaterials and Tissue Engineering

Supervisor (email): Assoc. Prof. Lucie Bačáková, MD, PhD (lucie.bacakova@fgu.cas.cz)

Laboratory website: https://fgu.cas.cz/en/research-and-laboratories/research-departments/laboratory-of-biomaterials-and-tissue-engineering/

PhD project: The effect of galectins and their inhibitors on vascular wall remodeling in pulmonary hypertension

This work will investigate the role of galectins in the onset and development of pulmonary hypertension (PH). A common feature of this heterogeneous disease, which has five subtypes, is pulmonary vascular remodeling that involves all cell types in the vascular wall, namely endothelial cells, smooth muscle cells, and fibroblasts. The mechanisms by which galectins influence changes in these cell types, and thus the development and progression of PH, are not yet fully understood. To investigate these mechanisms, we will focus on four specific galectins that regulate migration, proliferation, phenotypic modulation, inflammatory activation, and apoptosis of vascular wall cell types, namely galectin-1, -3, -8, and -9. Another important aim of this work will be to evaluate the therapeutic potential of glycopolymer galectin inhibitors, newly prepared in collaboration with the Institute of Microbiology of the Czech Academy of Sciences, using in vitro cell models. The results will be further verified in an in vivo rat model of PH induced by hypoxia or monocrotaline (in collaboration with the Laboratory of Developmental Cardiology, IPHYS, Prof. František Kolář). The overall aim of this work is to elucidate the mechanisms of PH pathophysiology related to individual galectins and to assess the potential of their pharmacological inhibition as a novel therapeutic strategy for PH.

PhD programme will be realized at the Ins􀆟tute of Physiology CAS. The work will be supported by the Praemium Academiae grant No. AP2202, the OP JAK ExRegMed project No. CZ.02.01.01/00/22_008/0004562, and also by the newly acquired GAČR grant No. 26-20451S „Pulmonary Hypertension: A Multitarget Approach Using Tailored Galectin Inhibitors.“

Candidate’s profile (requirements):

Graduate of a university with a focus on biology, master’s degree; languages: Czech, Slovak, English.

References:

Sedlář A, Bojarová P, Kolář F, Křen V, Bačáková L. Biomed Pharmacother. 2025;193:118756. doi: 10.1016/j.biopha.2025.118756.

Bačáková L, Sedlář A, Musílková J, Eckhardt A, Žaloudíková M, Kolář F, Maxová H. Physiol Res. 2024;73(S2):S569-S596. doi: 10.33549/physiolres.935394.

Sedlář A, Vrbata D, Pokorná K, Holzerová K, Červený J, Kočková O, Hlaváčková M, Doubková M, Musílková J, Křen V, Kolář F, Bačáková L, Bojarová P. J Med Chem. 2024;67(11):9214-9226. doi: 10.1021/acs.jmedchem.4c00341

Sedlář A, Trávníčková M, Bojarová P, Vlachová M, Slámová K, Křen V, Bačáková L. Int J Mol Sci. 2021;22(10):5144. doi: 10.3390/ijms22105144.

The role of hypoxia-inducible factor-1α on the progression of heart failure with preserved ejection fraction

Laboratory name: Laboratory of Experimental Hypertension

Supervisor (email): Jan Neckář, PhD (jan.neckar@fgu.cas.cz)

Laboratory website: https://fgu.cas.cz/en/research-and-laboratories/research-departments/laboratory-of-experimental-hypertension/

PhD project: The role of hypoxia-inducible factor-1α on the progression of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a multi-organ disease mainly affecting the heart, blood vessels, and kidneys. The development of new approaches for treating HFpEF is at the forefront of current cardiovascular research. We plan to investigate the role of transcription factor hypoxia-inducible-1α (HIF-1α), a key regulator of adaptation to oxygen deprivation with protective potential for various cardiovascular diseases, including HFpEF. This project will use a novel and unique rat strains with partial HIF-1α deficiency (heterozygous strains SD-HIF^+/- and SHR-HIF^+/-) and controls, i.e. Sprague-Dawley (SD) rat and spontaneously hypertensive rat (SHR). We will analyze the progression of HFpEF, cardiovascular and renal function, metabolic changes and end-organ damage, rats that will be treated with high-fat diet and will drink an inhibitor of nitric oxide synthase (established model HFpEF and cardiovascular-renal-metabolic syndrom). The project’s results may contribute to the development of novel therapeutic strategies for the treatment of HFpEF.

Candidate’s profile (requirements):

For this project, we seek students with a master’s degree in biomedical sciences (physiology, biochemistry and molecular biology, general medicine). We offer experimentally interesting and methodologically complex scientific work (echocardiography, telemetry, catheterization, electro-physiology, histology, modern molecular biology methods, omics) on a topic that is at the front-line of current experimental and clinical cardiovascular research. Our laboratory has extensive experience in cardiovascular research and successfully supervising PhD students. A Czech Science Foundation grant supports the project.

References:

Neckář J, Hsu A, Hye Khan MA et al., Infarct size-limiting effect of epoxyeicosatrienoic acid analog EET-B is mediated by hypoxia-inducible factor-1α via downregulation of prolyl hydroxylase 3. Am J Physiol Heart Circ Physiol. 2018;315(5):H1148-H1158.

Hojná S, Malínská H, Hüttl M et al., Hepatoprotective and cardioprotective effects of empagliflozin in spontaneously hypertensive rats fed a high-fat diet. Biomed Pharmacother. 2024;174:116520.

Neckář J, Hye Khan MA, Gross GJ et al., Epoxyeicosatrienoic acid analog EET-B attenuates post-myocardial infarction remodeling in spontaneously hypertensive rats. Clin Sci (Lond). 2019;133(8):939-951.

Sexual differences in protective effects of empagliflozin - the role of mTOR

Laboratory name: Laboratory of Experimental Hypertension

Project supervisor (email): RNDr. Ivana Vaněčková, DSc. (Ivana.Vaneckova@fgu.cas.cz)

Laboratory website: Laboratory of Experimental Hypertension – FGU

PhD project: Sexual differences in protective effects of empagliflozin – the role of mTOR

Large clinical trials support the existence of interactions between cardiovascular, metabolic and renal (CMR) diseases. Gliflozins (sodium-glucose cotransporter type 2 inhibitors) are considered the best example of drugs whose action is mediated by simultaneous intervention on various CMR mechanisms. Apart from their natriuretic and glycosuric effects, gliflozins have additional metabolic, anti-inflammatory, antifibrotic, and antioxidant effects. The mTOR (mammalian target of rapamycin) pathway regulates cell metabolism, growth and survival. Its dysregulation is associated with many diseases. The proposed project will investigate i) how gliflozins reprogram the cardio-metabo-renal axis via mTOR signaling pathway ii) whether there are sex differences in the effects of empagliflozin on cardiac, metabolic and renal parameters and iii) whether mTOR is the factor responsible for these effects.

Candidate’s profile (requirements):

We are looking for motivated candidates with master’s degree in molecular biology, biochemistry, physiology, or related fields. They should be fluent in English and interested in experimental research. We offer scientifically interesting and methodologically complex research projects (e.g., telemetry, echocardiography, catheterization, histology, and modern molecular biology methods) on a topic at the forefront of experimental and clinical cardiovascular research.

References:

Hojná S et al. Hepatoprotective and cardioprotective effects of empagliflozin in spontaneously hypertensive rats fed a high-fat diet. Biomed Pharmacother. 2024 May;174:116520.

Vaněčková I, Zicha J. Gliflozins in the Treatment of Non-diabetic Experimental Cardiovascular Diseases. Physiol Res. 2024 Apr 18;73(Suppl1):S377-S387

Hojná S et al: Antihypertensive and metabolic effects of empagliflozin in Ren-2 transgenic rats, an experimental non-diabetic model of hypertension. Biomed Pharmacother. 2021;144:112246.

Secretory function of epicardial adipose tissue and its role in the development of atrial fibrillations

Laboratory name: Laboratory of Adipose Tissue Biology

Supervisor (email): Petr Zouhar, Ph.D. (petr.zouhar@fgu.cas.cz)

Laboratory website: https://fgu.cas.cz/en/research-and-laboratories/research-departments/laboratory-of-adipose-tissue-biology/

PhD project: Secretory function of epicardial adipose tissue and its role in the development of atrial fibrillations

Adipose tissue secretes hormones, extracellular vesicles (EcV) and metabolites affecting other organs, including heart. Epicardial adipose tissue (eAT) may play particularly important role in heart physiology due to close vicinity to myocardium. The aims of this PhD thesis are:

To characterize the metabolome of eAT and pericardial fluid (which may be affected by secretion from eAT) using the unique biobank of samples of patients with heart failure and to investigate potential correlations with development of atrial fibrillations
To characterize composition of EcV in pericardial fluid (presumably largely secreted from eAT) and in peripheral blood of patients with heart failure
To characterize composition of EcV in murine circulation and in medium conditioned with explants of murine adipose tissue
To compare the composition of EcV in circulation of human and mice of several strains and both sexes
To investigate the effect of all the above-mentioned types of EcV on cell cultures of myotubes and cardiomyocytes

This approach will allow us to characterize the role of adipose tissue (particularly eAT) in pathophysiology of heart.

The PhD project will be realized at the Institute of Physiology of the Czech Academy of Sciences.

Candidate’s profile (requirements):

Self-motivated absolvent of MSc study program (or equivalent) in medicine, biology, biochemistry, or similar field, proficient in English. Previous experience with bioinformatics, biostatistics, cell cultures and wet lab would be considered an advantage.

References:

Janovska et al. 2020, J Cachexia Sarcopenia Muscle. doi: 10.1002/jcsm.12631. Epub 2020 Oct 20.

The role of mTOR signaling in cardiometabolic diseases

Laboratory name: Laboratory of Experimental Hypertension

Supervisor (email): RNDr. Ivana Vaněčková, DSc. (Ivana.Vaneckova@fgu.cas.cz)

Laboratory website: Laboratory of Experimental Hypertension – FGU

PhD project: The role of mTOR signaling in cardiometabolic diseases

Cardiometabolic disorders, including hypertension, type 2 diabetes, diabetic nephropathy and obesity, adversely affect the heart, liver and kidneys. The mTOR (mammalian target of rapamycin) pathway regulates cell metabolism, growth and survival. Its dysregulation is associated with many diseases. Abnormal mTOR signaling contributes to cardiometabolic disorders. Increased salt intake or high fat diet disrupts mTOR complex 1 (mTORC1), impairs renal function, exacerbates cardiac hypertrophy, and alters insulin signaling and lipid accumulation. Conversely, dysfunction of mTOR complex 2 (mTORC2) affects glucose homeostasis and vascular function.

Pharmacological modulation of mTOR complexes by their inhibitors or antihypertensives can alleviate hypertension and metabolic disorders, highlighting their therapeutic potential. This project integrates current findings on mTOR function in cardiometabolic disorders, which may provide new insights into therapeutic interventions for patients with cardiometabolic syndromes.

Candidate’s profile (requirements):

References:

Arora et al: Pathogenic Role of mTOR Signaling in Cardiometabolic Disease: Implications for Heart, Liver, and Kidney Dysfunction, Physiol Res, 74: 891-907, 2025

Arora M et al. Pharmacological effects of mTORC1/C2 inhibitor in a preclinical model of NASH progression. Biomed Pharmacother. 2023 Nov;167:115447.

Arora M et al. mTOR as an eligible molecular target for possible pharmacological treatment of nonalcoholic steatohepatitis. Eur J Pharmacol. 2022 Apr 15;921:174857.

Molecular mechanisms of cellular senescence-associated cardiovascular and renal diseases in hypertensive rats

Laboratory name: Laboratory of Experimental Hypertension

Supervisor (email): Jan Neckář, PhD (jan.neckar@fgu.cas.cz)

Laboratory website: https://fgu.cas.cz/en/research-and-laboratories/research-departments/laboratory-of-experimental-hypertension/

PhD project: Molecular mechanisms of cellular senescence-associated cardiovascular and renal diseases in hypertensive rats

Senescent cell accumulation is a fundamental aging process. In addition to aging, there is growing evidence that cellular senescence increases prevalence and contributes to the progression of many chronic diseases, including cardiovascular and renal (various forms of heart failure, coronary artery disease, hypertension, atherosclerosis, chronic kidney diseases, etc.). Eliminating senescent cells abrogated the senescence-associated secretory phenotype (mainly of proinflammatory cytokines and extracellular matrix modulators) and improved cardiac and renal functions. As a continuation of our ongoing research program, we will study the effect of cellular senescence on heart function, vascular and autonomic regulation, renal function, and end-organ damage in a unique knockout strain of spontaneously hypertensive rats (SHR) with targeted Tert (Telomerase reverse transcriptase). Homozygous SHR-Tert^-/- rats exhibit progressive telomere attrition in each generation, resulting in significant premature aging phenotype in the F3 generation. We will also study the role of intracellular signaling associated with Tert deficiency and the molecular and biological mechanisms of senescence. The impact of a partial deficiency of transcription factor hypoxia-inducible factor-1α (HIF-1α), a key regulator of adaptation to oxygen deprivation with protective potential for various cardiovascular diseases, will also be analyzed in aged (18 months) transgenic SHR strain (heterozygous SHR-HIF1a^+/-). Finally, we will study the prevention of senescence progression by new senolytic drugs based on alkyl triphenylphosphonium salts in cooperation with the Institute for Clinical and Experimental Medicine.

Candidate’s profile (requirements):

References:

Vacurová E, Vlachová E, Štursa J et al., Targeting mitochondrial Integrity as a new senolytic strategy.

Aging Dis. 2024;16(6):3638-3648.

Semenovykh K, Pravenec M, Vaněčková I, et al., Tert Deletion impairs circadian regulation of blood pressure in male spontaneously hypertensive rats. Hypertension. In press, 2026.

The effect of galectins and their inhibitors on vascular wall remodeling in pulmonary hypertension

Laboratory name: Laboratory of Biomaterials and Tissue Engineering

Supervisor (email): Assoc. Prof. Lucie Bačáková, MD, PhD (lucie.bacakova@fgu.cas.cz)

Laboratory website: https://fgu.cas.cz/en/research-and-laboratories/research-departments/laboratory-of-biomaterials-and-tissue-engineering/

PhD project: The effect of galectins and their inhibitors on vascular wall remodeling in pulmonary hypertension

Candidate’s profile (requirements):

Graduate of a university with a focus on biology, master’s degree; languages: Czech, Slovak, English.

References:

Sedlář A, Bojarová P, Kolář F, Křen V, Bačáková L. Biomed Pharmacother. 2025;193:118756. doi: 10.1016/j.biopha.2025.118756.

Bačáková L, Sedlář A, Musílková J, Eckhardt A, Žaloudíková M, Kolář F, Maxová H. Physiol Res. 2024;73(S2):S569-S596. doi: 10.33549/physiolres.935394.

Sedlář A, Trávníčková M, Bojarová P, Vlachová M, Slámová K, Křen V, Bačáková L. Int J Mol Sci. 2021;22(10):5144. doi: 10.3390/ijms22105144.

Biomimetic nanofibers supporting chronic wound healing

Laboratory name: Laboratory of Biomaterials and Tissue Engineering

Supervisor (email): Elena Filova, PhD, elena.filova@fgu.cas.cz

Laboratory website

MSc project: Biomimetic nanofibers supporting chronic wound healing

Chronic non-healing wounds have become a major health problem in the elderly population, often in association with diabetes. Chronic wounds show impaired cell proliferation, excessive extracellular matrix degradation, lower concentrations of growth factors, higher oxidative stress, etc. However, new bioactive materials are being developed that can stimulate chronic wound healing.

The aim of this study is to develop nanofiber dressings with a bioactive component and evaluate their ability to stimulate various cellular processes necessary for wound healing. It will include the effect of nanofibers on various skin cells such as keratinocytes, fibroblasts, endothelial cells and stem cells in mono- and co-cultures in vitro. The study will include the evaluation of cell adhesion, proliferation, differentiation/maturation, migration and ECM production in 2D and 3D environments, as well as the development and practical use of a chronic wound model in vitro.

Candidate’s profile (requirements):
The candidate should have a bachelor’s degree from a university with a focus on natural sciences, biomedical engineering, or a related field and be able to communicate in English.

References:

1. Táborská J, Blanquer A, Brynda E, Filová E, Stiborová L, Jenčová V, Havlíčková K, Riedelová Z, Riedel T. PLCL/PCL Dressings with Platelet Lysate and Growth Factors Embedded in Fibrin for Chronic Wound Regeneration. Int J Nanomedicine. 2023 Feb 3;18:595-610. doi: 10.2147/IJN.S393890. eCollection 2023.

2. Blanquer A, Kostakova EK, Filova E, Lisnenko M, Broz A, Mullerova J, Novotny V, Havlickova K, Jakubkova S, Hauzerova S, Heczkova B, Prochazkova R, Bacakova L, Jencova V. A novel bifunctional multilayered nanofibrous membrane combining polycaprolactone and poly (vinyl alcohol) enriched with platelet lysate for skin wound healing. Nanoscale. 2024 Jan 25;16(4):1924-1941. doi: 10.1039/d3nr04705a.

3. Adrian E, Treľová D, Filová E, Kumorek M, Lobaz V, Poreba R, Janoušková O, Pop-Georgievski O, Lacík I, Kubies D. Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads. Int J Mol Sci. 2021 Oct 28;22(21):11666. doi: 10.3390/ijms222111666.

4. Filova E, Blanquer A, Knitlova J, Plencner M, Jencova V, Koprivova B, Lisnenko M, Kostakova EK, Prochazkova R, Bacakova L.Nanomaterials (Basel). 2021 Apr 13;11(4):995. doi: 10.3390/nano11040995. The Effect of the Controlled Release of Platelet Lysate from PVA Nanomats on Keratinocytes, Endothelial Cells and Fibroblasts.

Enhancement of vascularized bone tissue formation using functionalized diamond scaffolds and electric stimulation

Laboratory name: Laboratory of Biomaterials and Tissue Engineering

Supervisor (email): Elena Filova, PhD, elena.filova@fgu.cas.cz

Laboratory website

PhD project: Enhancement of vascularized bone tissue formation using functionalized diamond scaffolds and electric stimulation

Guaranteeing workplace:

Institute of Physiology of the Czech Academy of Sciences, Department of Biomaterials and Tissue Engineering (Dr. Elena Filová)
Institute of Physics of the Czech Academy of Sciences, Department of Semiconductors (Dr. Štěpán Potocký

Bone defect healing and long-term function of the regenerated bone tissue are influenced by many factors, such as bone density, vascularization, defect size, presence of implant and its properties, infection, formation of fibrotic layer around the implant, other diseases of the patient, mechanical loading, etc. Stimulation of the formation of vascularized bone tissue using biomimetic materials and physical stimulation (electrical or mechanical) is important for improved bone tissue regeneration, osseointegration of bone prosthesis and its long-term function. Diamond layers are able to interact with various molecules and have been tested for their use in sensors. Further functionalization of the surface of the diamond layer will allow the establishment of specific interactions with both stem cells and endothelial cells, influencing cell adhesion, proliferation and differentiation, as well as creating an environment suitable for capillary formation.

The aim of the PhD thesis is to create an innovative biomimetic system, consisting of a three-dimensional porous scaffold covered with a functionalized diamond layer, that will stimulate human endothelial and mesenchymal stem cells and the formation of vascularized bone tissue in vitro by physical stimulation (electrical or mechanical) of the cells. In an interdisciplinary approach, in the biological part, it is possible to study cell adhesion, proliferation, and osteogenic differentiation of stem cells and the formation of capillary structures by endothelial cells. From the material point of view, it is possible to study the deposition and functionalization of diamond layers on porous scaffolds using plasma processes and subsequent characterization of the physical and chemical properties of the materials. Another possible aspect of the study is the influence of electrical or mechanical stimulation on stem cell and endothelial cell behavior and capillary formation.

Candidate’s profile (requirements):

A candidate should have a Master’s degree from a university in the natural sciences, biomedical engineering, or a related field, accept an interdisciplinary approach to the PhD program, and be able to communicate in English.

References:

Travnickova M, Vandrovcova M, Filova E, Steinerova M, Rackova J, Kocourek T, Bartova J, Suchy T, Zaloudkova M, Jelinek M, Bacakova L. Effect of diamond-like carbon doped with chromium on cell differentiation, immune activation and apoptosis. Eur Cell Mater. 2020 Nov 30;40:276-302. doi: 10.22203/eCM.v040a17. PMID: 33253412.

Steinerova M, Matejka R, Stepanovska J, Filova E, Stankova L, Rysova M, Martinova L, Dragounova H, Domonkos M, Artemenko A, Babchenko O, Otahal M, Bacakova L, Kromka A. Human osteoblast-like SAOS-2 cells on submicron-scale fibers coated with nanocrystalline diamond films. Mater Sci Eng C Mater Biol Appl. 2021 Feb;121:111792. doi: 10.1016/j.msec.2020.111792. Epub 2020 Dec 10. PMID: 33579442.

Travnickova M, Filova E, Slepicka P, Slepickova Kasalkova N, Kocourek T, Zaloudkova M, Suchy T, Bacakova L. Titanium-Doped Diamond-like Carbon Layers as a Promising Coating for Joint Replacements Supporting Osteogenic Differentiation of Mesenchymal Stem Cells. Int J Mol Sci. 2024 Feb 29;25(5):2837. doi: 10.3390/ijms25052837. PMID: 38474083; PMCID: PMC10932162.

The impact of biological sex on mitochondrial metabolism in cardiomyocytes

Laboratory name: Sex Chromosomes and Cardiometabolism

Supervisor (email): Lukáš Chmátal (chmatal@wi.mit.edu)

PhD Project: The impact of biological sex on mitochondrial metabolism in cardiomyocytes

Candidate’s profile (requirements):

References:

Maya Talukdar*, Lukas Chmátal*, Linyong Mao, Daniel Reichart, Danielle Murashige, Yelena Skaletsky, Daniel M. DeLaughter, Zoltan Arany, Jonathan G. Seidman, Christine Seidman, David C. Page. Genes of fatty acid oxidation pathway are upregulated in the female as compared to male human cardiomyocytes. Circulation (2025), *co-first authors

Daniel Reichart, Gregory A. Newby, Hiroko Wakimoto, Mingyue Lun, Joshua M. Gorham, Justin J. Curran, Aditya, Raguram, Daniel M. DeLaughter, David A. Conner, Júlia D. C. Marsiglia1, Sajeev Kohli, Lukas Chmátal, David C. Page, Nerea Zabaleta, Luk Vandenberghe, David R. Liu, Jonathan G. Seidman, and Christine Seidman. Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice. Nature Medicine, 29: 412-421 (2023)

Akera T., Chmátal L., Trimm E., Yang K., Aonbangkhen C., Chenoweth D.M., Janke C., Schultz R.M., Lampson M.A. Spindle asymmetry drives non-Mendelian chromosome segregation. Science, 358(6363): 668-672 (2017)

The impact of sex chromosomes on cardiometabolic adaptations during obesity

Laboratory name: Sex Chromosomes and Cardiometabolism

Supervisor (email): Lukáš Chmátal (chmatal@wi.mit.edu)

PhD Project: The impact of sex chromosomes on cardiometabolic adaptations during obesity

Heart disease is the leading cause of death worldwide, with significant differences in symptoms, prevalence, and outcomes between males and females. These sex differences are shaped by simultaneous contribution of various factors, including diet, exercise, sex hormones, and sex chromosomes. However, the specific impact of sex chromosomes, such as the “inactive” X chromosome (Xi) in females and the Y chromosome in males, on heart physiology and function remains poorly understood. To address this knowledge gap, we ask: How does the Xi regulate mitochondrial functions under normal and pathological conditions? To tackle this question, we have developed the MiCY* mouse model characterized by altered sex chromosome compositions, combined with established model with cardiomyocyte-specific fluorescently tagged outer mitochondrial membrane protein. This MiCY* mouse model allows us to isolate mitochondria specifically from cardiomyocytes, and study the effects of the Xi on mitochondrial physiology and function under both normal and obesity-related conditions. Using an integrated approach that combines heart physiology techniques, biochemistry, targeted and untargeted metabolomics, proteomics, and fluorescence microscopy, we will explore the role of the Xi chromosome and specific Xi-expressed genes in mitochondrial biology during both health and disease. This work will provide critical insights into how the Xi chromosome influences mitochondrial metabolism and contributes to cardiac health and disease.

Candidate’s profile (requirements):

You have completed, or are nearing the completion of, a Master’s degree in biological, medical, chemical, or biochemical sciences. You bring motivation, attention to detail, and hands-on experience in cell biology, molecular biology, or metabolomics. You are comfortable with handling mouse and human samples. You are fluent in English, have excellent communication skills and thrive in an inclusive, collaborative and supportive team that works towards a shared goal.

References:

The role of hypoxia-inducible factor-1α on the progression of heart failure with preserved ejection fraction

Laboratory name: Experimental Hypertension

Supervisor (email): Jan Neckář, jan.neckar@fgu.cas.cz

Laboratory website

PhD project: The role of hypoxia-inducible factor-1α on the progression of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a complex, multi-organ disease affecting the heart, vasculature, and kidneys. Since the prevalence of HFpEF in the population has increased, developing new treatment approaches is at the forefront of current cardiovascular research. This project will explore the role of transcription factor hypoxia-inducible-1α (HIF-1α), a key regulator of adaptation to oxygen deprivation with protective potential for various cardiovascular diseases, in HFpEF progression. Using a novel and unique rat strain with partial HIF-1α deficiency (heterozygous SD-HIF^+/-), we will investigate the progression of HFpEF, focusing on cardiovascular and renal function, as well as end-organ damage, under a high-fat diet and nitric oxide synthase inhibition (established HFpEF model) in the SD-HIF^+/- and Sprague-Dawley (SD) controls. The project’s results may contribute to the development of novel therapeutic strategies for the treatment of HFpEF.

Candidate’s profile (requirements):

For this project, we seek students with a master’s degree in biomedical sciences (physiology, biochemistry and molecular biology, general medicine). We offer experimentally interesting and methodologically complex scientific work (echocardiography, telemetry, catheterization, electro-physiology, histology, modern molecular-biological methods, omics) on a topic at the front-line of current experimental and clinical cardiovascular research. Our laboratory has extensive experience in cardiovascular research and successfully supervises PhD students. A Czech Science Foundation grant supports the project.

References:

Hojná S, Malínská H, Hüttl M, Vaňourková Z, Marková I, Miklánková D, Hrdlička J, Papoušek F, Neckář J, Kujal P, Behuliak M, Rauchová H, Kadlecová M, Sedmera D, Neffeová K, Zábrodská E, Olejníčková V, Zicha J, Vaněčková I. Hepatoprotective and cardioprotective effects of empagliflozin in spontaneously hypertensive rats fed a high-fat diet. Biomed Pharmacother. 2024;174:116520.

Neckář J, Hsu A, Hye Khan MA, Gross GJ, Nithipatikom K, Cyprová M, Benák D, Hlaváčková M, Sotáková-Kašparová D, Falck JR, Sedmera D, Kolář F, Imig JD. Infarct size-limiting effect of epoxyeicosatrienoic acid analog EET-B is mediated by hypoxia-inducible factor-1α via downregulation of prolyl hydroxylase 3. Am J Physiol Heart Circ Physiol. 2018;315(5):H1148-H1158.

Cellular senescence-associated cardiovascular and renal diseases in hypertensive rats

Laboratory name: Experimental Hypertension

Supervisor (email): Jan Neckář, jan.neckar@fgu.cas.cz

Laboratory website

PhD project: Cellular senescence-associated cardiovascular and renal diseases in hypertensive rats

Senescent cell accumulation is a fundamental aging process. In addition to aging, there is growing evidence that cellular senescence increases prevalence and contributes to the progression of many chronic diseases, including cardiovascular and renal (various forms of heart failure, coronary artery disease, hypertension, atherosclerosis, chronic kidney diseases, etc.). Eliminating senescent cells abrogated the senescence-associated secretory phenotype (mainly of proinflammatory cytokines and extracellular matrix modulators) and improved cardiac and renal functions. As a continuation of our ongoing research program, we will study the effect of cellular senescence on heart and renal function, vascular and autonomic regulation, and end-organ damage in a unique knockout strain of spontaneously hypertensive rats (SHR) with targeted Tert (Telomerase reverse transcriptase). Homozygous SHR-Tert^-/- rats exhibit progressive telomere attrition in each generation, resulting in significant premature aging phenotype in the F3 generation. We will also study the role of intracellular signaling associated with Tert deficiency and the molecular and biological mechanisms of senescence. The impact of a partial deficiency of transcription factor hypoxia-inducible factor-1α (HIF-1α), a key regulator of adaptation to oxygen deprivation with protective potential for various cardiovascular diseases, will also be analyzed in aged (18 months) transgenic SHR strain (heterozygous SHR-HIF1a^+/-). Finally, we plan to study the prevention of senescence progression by new senolytic drugs based on alkyl triphenylphosphonium salts in cooperation with the Institute for Clinical and Experimental Medicine (Dr. Štemberková Hubáčková group).

Candidate’s profile (requirements):

For this project, we seek students with a master’s degree in biomedical sciences (physiology, biochemistry and molecular biology, general medicine). We offer experimentally interesting and methodologically complex scientific work (echocardiography, telemetry, catheterization, electro-physiology, histology, modern molecular-biological methods, omics) on a topic at the front-line of current experimental and clinical cardiovascular research. Our laboratory has extensive experience in cardiovascular research and successfully supervises PhD students. A Czech Science Foundation grant supports the project.

References:

Vacurova E, Trnovska J, Svoboda P, Skop V, Novosadova V, Reguera DP, Petrezselyová S, Piavaux B, Endaya B, Spoutil F, Zudova D, Stursa J, Melcova M, Bielcikova Z, Werner L, Prochazka J, Sedlacek R, Huttl M, Hubackova SS, Haluzik M, Neuzil J. Mitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice. Nat Commun. 2022;13(1):1866.

Neckář J, Hye Khan MA, Gross GJ, Cyprová M, Hrdlička J, Kvasilová A, Falck JR, Campbell WB, Sedláková L, Škutová Š, Olejníčková V, Gregorovičová M, Sedmera D, Kolář F, Imig JD. Epoxyeicosatrienoic acid analog EET-B attenuates post-myocardial infarction remodeling in spontaneously hypertensive rats. Clin Sci (Lond). 2019;133(8):939-951.

Mechanisms of protective effects of empagliflozin – the role of HIF-1α

Laboratory name: Experimental Hypertension

Supervisor (email): Ivana Vaněčková, ivana.vaneckova@fgu.cas.cz

Laboratory website

PhD project: Mechanisms of protective effects of empagliflozin – the role of HIF-1α

Gliflozins, the inhibitors of sodium-glucose cotransporter type-2 (SGLT-2), are primarily antidiabetics, whose benefits have been demonstrated in many cardiovascular diseases. Although the principle mechanism of actions of SGLT-2 inhibitors is known – the blockade of the sodium-glucose co-transporter in the proximal tubule, leading to glycosuria and natriuresis – there are additional metabolic as well as anti-inflammatory and anti-oxidant effects beyond. In this context, the role of hypoxia-inducible factor-1α (HIF-1α) is newly discussed as the potential mechanism underlying gliflozin’s beneficial effects. Hypoxia-inducible factors belong to transcription factors that control the transcription rate of genes involved in angiogenesis, metabolism, erythropoiesis, and apoptosis, as well as inflammation and fibrosis, their effects being dependent on the oxygen level. Using two unique rat strains – HIF-1α knockouts – we will analyze whether HIF1α is the underlying factor responsible for the beneficial effects of empagliflozin under normoxic and hypoxic conditions. We shall investigate the effects of chronic empagliflozin treatment on cardiac, hepatic, metabolic, and renal parameters in normotensive and hypertensive rat strains fed a diet rich in fat, fructose, and cholesterol with a focus on the role of HIF-1α and hypoxia in its beneficial actions.

Candidate’s profile (requirements):

For this project, we seek students with a master’s degree in biomedical sciences (physiology, biochemistry and molecular biology, general medicine). We offer experimentally interesting and methodologically complex scientific work (from whole body to molecular biology methods) on a hot topic in contemporary biomedical experimental and clinical research. Our laboratory has extensive experience in cardiovascular research and successfully supervising PhD students.

References:

Malínská H, Hüttl M, Marková I, Miklánková D, Hojná S, Papoušek F, Šilhavý J, Mlejnek P, Zicha J, Hrdlička J, Pravenec M, Vaněčková I. Beneficial effects of empagliflozin are mediated by reduced renal inflammation and oxidative stress in spontaneously hypertensive rats expressing human C-reactive protein. Biomedicines. 2022;10(9):2066.

Hojná S, Rauchová H, Malínská H, Marková I, Hüttl M, Papoušek F, Behuliak M, Miklánková D, Vaňourková Z, Neckář J, Kadlecová M, Kujal P, Zicha J, Vaněčková I. Antihypertensive and metabolic effects of empagliflozin in Ren-2 transgenic rats, an experimental non-diabetic model of hypertension. Biomed Pharmacother. 2021;144:112246.