8.2. 2023, Bioenergetika

Laboratory name: Bioenergetics

Laboratory website

PhD project: Adaptations of cellular metabolism to dysfunction of mitochondrial oxidative phosphorylation

Mitochondria play an important role in ATP production and cellular homeostasis by provision of intermediates for biosynthetic pathways. In humans, the defects of oxidative phosphorylation (OXPHOS) lead to severe mitochondrial diseases, affecting tissues with high energetic demands. In order to maintain ATP and carbon homeostasis, diseased cells need to reconfigure their metabolic pathways (known as metabolic rewiring). Dual genetic origin of OXPHOS enzymes hampers development of primary gene therapy, which triggered intensive research aimed at identification of disease modifying agents able to alleviate metabolic stress. However, the spectrum of metabolic adaptations is very broad depending on type and severity of the defect.

In the current project, we will study unique mammalian models with primary defects of oxidative phosphorylation. Using modern metabolomic and proteomic approaches, we aim to identify metabolic fingerprints in these models that would allow us to define key metabolic pathways that could be used as therapeutic targets in the future.

References:

Pecinová A et al. Role of Mitochondrial Glycerol-3-Phosphate Dehydrogenase in Metabolic Adaptations of Prostate Cancer. Cells. 2020 Jul 23;9(8):1764
Pajuelo Reguera D et al. Cytochrome c Oxidase Subunit 4 Isoform Exchange Results in Modulation of Oxygen Affinity. Cells. 2020 Feb 14;9(2):443
Nuskova H et al. Biochemical thresholds for pathological presentation of ATP synthase deficiencies. Biochem Biophys Res Commun. 2020 Jan 22;521(4):1036-1041.

Supervisor (email): RNDr. Alena Pecinová, Ph.D. (alena.pecinova@fgu.cas.cz)

Candidate’s profile (requirements): We are seeking highly motivated person with master’s degree or equivalent in cell biology, biochemistry, physiology or similar field obtained before or during 2023. Candidate should be fluent in English and enthusiastic about mitochondria. Experience with cell cultures and molecular biology approaches is an advantage.