Intranet

Fyziologický ústav AV ČR

Špičková věda pro zdraví

New metabolic pathways involved in synthesis of anti-diabetic lipids

Laboratory of Metabolism of Biactive Lipids

PhD project: New metabolic pathways involved in synthesis of anti-diabetic lipids

The focus of our lab is the metabolism and regulatory actions of bioactive lipids, specifically those related to pathways of glucose and lipid metabolism. We are interested in products of de novo lipogenesis such as branched fatty acid esters of hydroxy fatty acids (FAHFA), in anti-inflammatory & pro-resolving eicosanoids and docosanoids, and in endocannabinoid-like metabolites derived from omega-3 polyunsaturated fatty acids.

The aim of this project is to identify metabolic pathways of FAHFA synthesis and degradation in (patho)physiological states. First, we will combine biochemistry, analytical chemistry and metabolic flux analysis to characterize regulation of the DNL pathway and formation of the lipokines. We will apply state of the art LC-MS/MS metabolomics and lipidomics methods using 13C- and 2H-labeled metabolites/tracers on adipocytes and hepatocytes. Second, we will examine the metabolite pools of PAHSAs and their regulation of lipolysis using murine genetic and dietary models.

The project can be focused either on chemistry (analytical chemistry, biochemistry) or on animal physiology and molecular biology based on the candidate‘s background. The student could also undergo short-term visits at the collaborating institute(s).

Candidate’s profile (requirements):

We are looking for curious, imaginative, independent and highly-motivated applicants holding a master’s degree (or those expecting to obtain their degree this year) with experience in (bio)chemistry or physiology/medicine or molecular biology. The position is open for the graduates, but skills in any of the following: bioinformatics/programing, whole animal physiology, LC-MS/MS are an advantage and/or can be learned in the lab.

Supervisor: Ondrej Kuda, Ph.D. (ondrej.kuda@fgu.cas.cz)

Relevant publications:

  1. Paluchova et al., Lipokine 5-PAHSA is Regulated by Adipose Triglyceride Lipase and Primes Adipocytes for de novo Lipogenesis in Mice. Diabetes. 2019 Dec 5. pii: db190494. doi: 10.2337/db19-0494
  2. Brezinova et al., Exercise training induces insulin-sensitizing PAHSAs in adipose tissue of elderly women. Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Nov 16;1865(2):158576. doi: 10.1016/j.bbalip.2019.158576
  3. Kuda et al., Nrf2-Mediated Antioxidant Defense and Peroxiredoxin 6 Are Linked to Biosynthesis of Palmitic Acid Ester of 9-Hydroxystearic Acid. Diabetes. 2018 Jun;67(6):1190-1199. doi: 10.2337/db17-1087
  4. Brezinova et al., Levels of palmitic acid ester of hydroxystearic acid (PAHSA) are reduced in the breast milk of obese mothers. Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Feb;1863(2):126-131. doi: 10.1016/j.bbalip.2017.11.004