2.2. 2023, Výzkum pankreatických ostrůvků

Laboratory name: Pancreatic Islet Research

Laboratory website

PhD project: The role of glucose-stimulated redox and lipid signaling in the physiology and pathology of pancreatic beta cells

Our newly established laboratory studies the physiology and pathophysiology of pancreatic beta cells. Beta cells are the guardians of glucose homeostasis in the body, and their deficiency and impaired function trigger the development of diabetes. We focus on the role of redox homeostasis and lipid metabolism during glucose stimulation and subsequent signaling. Altered redox status and glucose-induced lipid metabolism can affect cellular signaling while in the long-term can induce cellular stress. The switching point and metabolic targets of signaling are unknown in the beta cells.

The goal of this PhD project is to identify and investigate the targets of pro-oxidant redox signaling upon glucose stimulation of beta cells and to uncover the mechanism of how excessive reactive oxygen species production causes the diabetic phenotype. Similarly, the identification of glucose-induced lipid signaling and lipid metabolism under conditions of insulin secretion on the one hand, and the mechanism of their dysregulation to develop diabetes on the other, will be investigated. A unique mouse model with altered redox status in beta cells and isolated Langerhans cells will be used for the study, employing novel experimental strategies in combination with omics analysis.

References:

Plecita-Hlavata L, Jaburek M, Holendova B, Tauber J, Pavluch V, Berkova Z, et al. Glucose-Stimulated Insulin Secretion Fundamentally Requires H2O2 Signaling by NADPH Oxidase 4. Diabetes. 2020.

Plecita-Hlavata L, Engstova H, Holendova B, Tauber J, Spacek T, Petraskova L, et al. Mitochondrial Superoxide Production Decreases on Glucose-Stimulated Insulin Secretion in Pancreatic beta Cells Due to Decreasing Mitochondrial Matrix NADH/NAD(+) Ratio. Antioxid Redox Signal. 2020;33(12):789-815.

Benakova S, Holendova B, Plecita-Hlavata L. Redox Homeostasis in Pancreatic beta-Cells: From Development to Failure. Antioxidants (Basel). 2021;10(4).

Supervisor (email): lydie.plecita@fgu.cas.cz

Candidate’s profile (requirements): We are seeking talented and motivated biological problem-solving graduates with a background in biological and biomedical sciences and computational biology. Experience with cell culture, mouse/rat models, molecular biology and biochemistry, omics data analysis, and computational biology is an advantage.