15:00 -15:15 Michal Knězů – Bioenergetics
Thesis: Regulation of mitochondrial oxidative phosphorylation by tissue-specific isoforms of cytochrome c oxidase
Annotation: Mitochondrial cytochrome c oxidase (COX) is a key enzyme of oxidative phosphorylation (OXPHOS) system responsible for ATP production in mammalian cells. Expression of tissue-specific isoforms of COX subunits represents a crucial mechanism of OXPHOS regulation. Recently, our studies helped establish the lung isoform of regulatory subunit 4 (COX4I2) as a key component of functionally modified COX with reduced oxygen affinity dedicated to oxygen sensing. Our focus is now expanded to subunit COX6B that occurs either as ubiquitous isoform (COX6B1) or as a protein with exclusive testicular expression (COX6B2). Also, ectopic COX6B2 expression was associated with poor prognosis of lung carcinoma (LC). The project aims to explore the understudied phenomenon of COX6B isoform exchange and its effect on structure and function of OXPHOS. COX6B knock-out/knock-in models will be constructed in HEK293 and LC cell lines to characterize basic functional features of subunit isoforms and their impact on proliferation and tumorigenesis of LC. The role COX6B2 and its post-translational modification will also be studied in the physiological context of sperm maturation and capacitation. The proposed research will provide novel data on OXPHOS biogenesis and regulation and the role of these processes in carcinogenesis and male fertility.
15:15 – 15:30 Jayashri Bhosale – Laboratory of Structural Biology of Signaling Proteins
Thesis: Mechanistic insight into the regulation of apoptotic signaling pathways
Annotation: Apoptosis is a highly regulated process, crucial for controlling cell growth. The members of MAP kinase family are pivotal in apoptotic signaling, as well as in growth and differentiation and widely used throughout evolution to maintain many physiological processes. ASK1, a member of the MAP3K family, is a key therapeutic target regulated by partners like thioredoxin (TRX1), tumor necrosis factor-associated factors (TRAF) 2/5/6, and the scaffolding protein 14-3-3. Despite many years of intensive research, there is no atomic resolution structure of multi-domain ASK1 in complex with 14-3-3 or TRX1, which has hindered functional and mechanistic understanding of ASK1 regulation. The aim of this project is the biophysical and structural characterization of the ASK1:TRX1 and ASK1:14-3-3 complexes using a combination of hydrogen-deuterium exchange coupled mass spectrometry (HDX-MS), cryo-electron microscopy (cryo-EM) and sedimentation velocity analytical ultracentrifugation (SV-AUC). With this detailed insight, we can consider ASK1 as a promising target for therapeutic purpose in future.
Contact at IPHYS: Petra Alánová, D.Sc., Ph.D., petra.alanova@fgu.cas.cz
