Robin Klemm - Cell Physiology - 'How do adipocytes transport fatty acids across the cell surface?'

How fat tissue secretes fatty acids during times of starvation is a big unanswered question in cell physiology. In fact, we know in general relatively little about the mechanisms that traffic free fatty acids into and out of cells. In your project, we tackle this problem with a tissue culture model for adipocytes, using a combination of light and electron microscopy, structural biology, easy metabolite analysis, cell biology and CRISPR-genetics. The experimental set up is easily tractable because the secretion of fatty acids can be readily induced by addition of a small molecule to differentiated adipocytes. You will focus on studying the intracellular re-arrangement of organelles during lipolysis. We will investigate how the lipid storage organelles called lipid droplets are hooked to the cell surface and how this is coupled to efficient secretion of newly mobilized fatty acids. This will be analyzed by light and electron-microscopy, and metabolic essays. To identify factors that move the lipid droplets around in the cell we are going to use organelle purification and proximity specific proteomics methods. A candidate library of potentially important factors will then be subjected to a targeted genetic screen in which we aim to find the machinery that transports fatty acids outside of the cell. These mechanisms have fundamental relevance in systemic energy metabolism and will help to understand the pathophysiology of obesity and diabetes.