13.1. 2020, Laboratory of Mitochondrial Physiology

Laboratory of Mitochondrial Physiology 

PhD project: Role of Inhibitory Factor IF1 in the regulation of pancreatic β-cell metabolism and mitochondrial morphology

A unique function of pancreatic β-cells is insulin secretion and consequently also maintenance of glucose homeostasis. Several factors ensure precise coupling of glucose levels, pancreatic β-cells metabolism and insulin secretion. ATP is recognized as a key regulator of insulin secretion. Studies addressing intrinsic regulators of ATP synthase in pancreatic beta cells are thus of paramount importance and have a high potential of identifying new T2DM therapeutical targets. Surprisingly, nearly no studies are available in this research field. Recently, we reported on the presence of ATPase inhibitory factor 1 (IF1) in pancreatic β-cells and its role in downregulation of cellular ATP levels and insulin secretion [1]. However, the exact mechanism by which IF1 regulates ATP synthesis remains controversial and further studies are essential.

The aim of this PhD project is to study the mechanism by which IF1 regulates ATP levels in pancreatic β-cells and to identify post-translational modification of IF1 in response to glucose availability. Selected PhD student will also analyze how IF1 regulates insulin secretion in vivo by use of IF1-knockout mouse model. To study changes in mitochondrial morphology newest super-resolution microscopy techniques and 3D electron microscopy techniques will be applied.

Candidate’s profile (requirements):

We are seeking outstanding self-motivated candidates with a master's degree or equivalent in molecular biology, biochemistry, or related fields. Candidates should be fluent in English.

Supervisor: Andrea Dlaskova, Ph.D. (andrea.dlaskova@fgu.cas.cz)

Relevant publications:

•Kahancová A, Sklenář F, Ježek P, Dlasková A. Regulation of glucose-stimulated insulin secretion by ATPase Inhibitory Factor 1 (IF1). FEBS Lett. 2018. Mar;592(6):999-1009. doi: 10.1002/1873-3468.12991