11.1. 2016, Bioenergetika

We are seeking for up to three PhD students, working on (1) biogenesis of ATP synthase and (2) adaptations of mitochondrial metabolism under cellular stress or cancer. These students will join the team of the department of bioenergetics, Institute of physiology CAS.

Main focus of the 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.

The PhD programme at the Institute of Physiology CAS is part of a joint biomedical PhD programme organised by Charles University and Czech Academy of Sciences. PhD students are enrolled at Charles University, usually within the Faculty of Science or the First Faculty of Medicine. During the programme, students attend recommended courses, organised by graduate boards or directly by the institutes. In addition, students are encouraged to present their data at international conferences and attend workshops relevant for their field. Participation is covered by the departmental budget.

 

 

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; Hejzlarova et al., BBA 1807: 144, 2011; Kratochvilova et al., Mitochondrion 15: 1, 2014). This project should build on this knowledge and using of cellular models 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 establish 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. Knowledge of/willingness to learn HTS screening approaches and subsequent data analysis is an asset.

Supervisor: RNDr. Tomáš Mráček, Ph.D.

 

 

 

PhD project 2: Mitochondrial glycerol-3-phosphate dehydrogenase as a target for anti-tumour therapies

Mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase (mGPDH) is inducible and highly tissue/cell specific enzyme typically active in glycolytic cells (Mracek et al., BBA 1827: 401, 2013; Mracek et al., BBA 1837: 98, 2014). As such it is also elevated in some tumours. Main aim of this project is to explore biochemical properties and expression patterns of mGPDH in various tissues and tumour types. Project will explore potential inhibitors of mGPDH, characterise their action on the enzyme and test their potential as anti-tumour agents. Project will include work on tumour cell lines, biochemical characterisation of inhibitors’ mode of action and data mining for tumour types, which are dependent on mGPDH.

Candidate’s profile (requirements): MSc or MD degree in biochemistry or similar field. Candidates should be experienced in biochemistry and cell biology techniques, working knowledge of enzyme purification techniques and activity assays is an advantage.

Supervisor:     RNDr. Alena Pecinová, 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 FGU core) and proteomics data (generated at Biocev core) to pinpoint pro-survival pathways in various cancer cell lines/cell lines with mitochondrial defects. Subsequently these data will be functionally validated by potential inhibitors.

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

Supervisor:     RNDr. Tomáš Mráček, Ph.D. or RNDr. Alena Pecinová, Ph.D.

Contact: tomas.mracek@fgu.cas.cz, alena.pecinova@fgu.cas.cz