8.2. 2023, Bioenergetika

Laboratory name: Bioenergetics

Laboratory website

PhD project: Targeting mitochondrial fatty acid oxidation and adipose tissue browning to prevent obesity

Almost 60% of the European Union population is overweight with around 25% obese people. Higher BMI is a major risk factor for metabolic disorders such as type 2 diabetes mellitus, hypertension, and cardiovascular diseases. There are several possibilities of obesity treatment, but they mostly rely on the active approach of the affected person (dietary changes, physical activity, recovery after surgery, weight loss medication). Among other therapies, hormonal treatment or browning of white fat cells represent easier approaches for the patients. The browning is accompanied by mitochondrial biogenesis and increased capacity for fatty acid oxidation. Our laboratory has a long-standing history of mitochondrial bioenergetic research and has been currently expanding to the fields of metabolism and proteomic research.

In the proposed project, we would like to study the role of mitochondrial proteins in browning of subcutaneous adipose tissue and to uncover their potential for treating obesity and metabolic syndrome. The study will be performed in various experimental models e.g., cellular KO´s, primary cell lines and mouse KO models. For example, we will use models with genetically eliminated Vwa8 protein, which in Hek 293 cells shows respiration-dependent substrate preference toward mitochondrial fatty acid oxidation and on the animal model is characterized by browning of subcutaneous adipose tissue, increase in fatty acid oxidation and improved insulin sensitivity. Overall, the topic will cover broad spectra of genetic (CrisprCas9 KO generation), biochemical (mitochondrial respiration, SDS and native-PAGE) and physiological (metabolic cages, insulin, and glucose measurements) approaches.

References:

1.   Bean C, Audano M, Varanita T, Favaretto F, Medaglia M, Gerdol M, Pernas L, Stasi F, Giacomello M, Herkenne S, Muniandy M, Heinonen S, Cazaly E, Ollikainen M, Milan G, Pallavicini A, Pietiläinen KH, Vettor R, Mitro N, Scorrano L.: The mitochondrial protein Opa1 promotes adipocyte browning that is dependent on urea cycle metabolites. Nat Metab. 2021 Dec;3(12):1633-1647. doi: 10.1038/s42255-021-00497-2.

2.   Alan L, Scorrano L.: Shaping fuel utilization by mitochondria. Curr Biol. 2022 Jun 20;32(12):R618-R623.

Supervisor (email): Ass. Prof. Lukáš Alán, PhD (lukas.alan@fgu.cas.cz)

Candidate’s profile (requirements): We are looking for a highly motivated person with MSc. or equivalent degree in cell biology, biochemistry, physiology, or similar field obtained before or during 2023. Candidate should be fluent in English, enthusiastic for science, curious and with positive mindset.