11.1. 2016, Bioenergetika

Research topic:

Main focus of our department lies on mitochondria, an organelle which accommodates number of key metabolic pathways and governs the live and death of the cell. A lot of our Research goes into the complexes of oxidative phosphorylation apparatus (OXPHOS), regulation of their biogenesis, specific assembly factors and disease causing mutations responsible for rare mitochondrial diseases – mitopathies.

 

PhD project 1:

Factors involved in the regulation of mammalian mitochondrial ATP synthase biogenesis.

Our team was involved in the description and subsequent characterisation of TMEM70 protein acting as assembly factor for ATP synthase (Cizkova et al., Nat Genet 40: 1288, 2008; Kratochvilova et al., Mitochondrion 15: 1, 2014; Vrbacky et al., Hum Mol Gen, 2016). Using mouse model of inducible TMEM70 knockout and cellular knockout models we want to elucidate true TMEM70 function and to search for potential new factors involved in regulation of ATP synthase biogenesis.

Second part of the project will explore possible pharmacological complementation of ATP synthase assembly defects. Especially TMEM70 represents promising target for establishing of new therapy as it is not absolutely essential for ATP synthase biogenesis and sufficient recovery of ATP production can be expected even after partial increase of ATP synthase content. The aim will be to screen for pharmacological activators of ATP synthesis on a model of TMEM70 knockout cells and subsequently test candidate compounds on a collection of patients’ fibroblasts cell lines harbouring mutations in TMEM70.

Candidate’s profile (requirements): MSc or MD degree in biochemistry, pharmacology or similar field. Candidates should have a good track record in biochemistry, cell biology and molecular biology techniques.

Supervisor: RNDr. Tomáš Mráček, Ph.D.

 

PhD project 2:

Usmg5 role in ATP synthase biogenesis and development of metabolic phenotypes.

In collaboration with the department of genetics of model diseases we have developed rat knockout of Usmg5 protein – one of the recently described subunits of mammalian ATP synthase. Surprisingly, these animals show marked improvement in metabolic phenotypes, including lower adiposity and improved insulin sensitivity. The aim of this project is to perform initial biochemical characterisation of mitochondrial function and to further dig into the adaptations occurring at the whole body level to understand the role of ATP synthase in modulation of metabolic plasticity. This project should take the advantage of wide array of phenotypisation techniques available at the Institute of Physiology and adapt them for the use on mitochondrial models.

Candidate’s profile (requirements): MSc or MD degree in (animal) physiology or similar. Candidates should have a good track record in physiology and also biochemistry. Willingness to work with laboratory animals is requirement, previous experience strong asset.

Supervisor: RNDr. Tomáš Mráček, Ph.D.

 

PhD project 3:

omics approaches to deciphering adaptations of mitochondrial metabolism

Mitochondrial metabolism displays considerable plasticity and can adapt to external constrains, e.g. as we have demonstrated for leukemic cells treated with L-asparaginase (Hermanova et al., Leukemia 30:209-18, 2016). This project should combine data from measurements of cellular respiration/glycolysis with metabolomics data (generated at the IPHYS core) to pinpoint pro-survival pathways in various cancer cell lines that depend on functional mitochondria. Candidate should work closely with the metabolomics core staff and contribute to the development of fluxomic analysis of mitochondrial metabolism.

Candidate’s profile (requirements): MSc or equivalent degree in cell biology, biochemistry or analytical chemistry. Apart from the experimental “wet” work, candidates should be willing to learn data processing and analysis techniques and adapt them to project’s needs.

Supervisor: RNDr. Alena Pecinová, Ph.D.