2.2. 2023, Biologie tukové tkáně

Laboratory name:  Adipose tissue biology

Laboratory website  

PhD project: Role of non-shivering thermogenesis in skeletal muscle in cold and obesity resistance

Non-shivering thermogenesis (NST) is involved in energy balance, with UCP1-mediated NST in brown fat playing an important role even in humans. Alternative mechanisms of NS exist and need to be better characterized, namely NST in skeletal muscle. Mitochondrial oxidative phosphorylation (OXPHS) and futile calcium cycling in muscle cells may be involved in and contribute to different propensity to obesity in inbread strains (C57Bl/6 vs A/J) of mice. Our results suggest that C57Bl/6 mice exhibit low muscle NST due to mutation in Scaf1 (Cox7a2l) gene causing lack of formation of mitochondrial supercomplexes and compromised OXPHOS.

This project has two major aims:

To optimize mechanomyography technique as a new sensitive method for assessment of classical shivering thermogenesis, using a novel already introduced measuring system.
To characterize the role of mitochondrial supercomplex formation in adaptive muscle NST using transgenic C57Bl/6 mice overexpressing functional Scaf1 specifically in muscle.

      3.   To characterize mechanisms engaged in acute control of NST in skeletal muscle, which are

             completely unknown.

Besides the classical laboratory techniques of biochemistry and molecular biology, this project will involve in particular broad range of techniques of in vivo phenotyping. Results will be important for (i) uncovering basic biological mechanisms engaged in energy homeostasis and thermogenesis and (ii) identification of new targets to treat obesity.

References:

·Benegiamo G. et al, COX7A2L genetic variants determine cardiorespiratory fitness in mice and human, Nature Metab 2022; 4: 1336–1351.
·Chouchani E. et al., New Advances in Adaptive Thermogenesis: UCP1 and Beyond, Cell Metab 2019; 29(1):27-37.
·Flachs P. et al., Induction of lipogenesis in white fat during cold exposure in mice: link to lean phenotype, Int J Obes (Lond) 2017; 41(6):997.

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

Candidate’s profile (requirements): 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 should be fluent in English. Experience with handling laboratory mice, in vitro cell cultures and/or molecular biology techniques are advantage.

Financial support: Regular stipend at university supplemented by a salary from the National Institute for Metabolic and Cardiovascular Disease Research project (https://cardia.ikem.cz/en/home).