Research:   

Our research focuses on fundamental questions of the regulation of organismic metabolism in general and the storage of energy rich lipids in particular:

  • How do cells and organisms regulate their lipid storage amounts?
  • How and why are different "setpoints" achieved?
  • How are intracellular lipids stored mechanistically?

The storage of energy rich lipids is a universal feature of organisms. It allows survival of conditions with limited nutrient supply as well as times of elevated energy demand. Yet, lipid storage levels need to be tightly controlled. This is most easily seen in emerging metabolic diseases of man such as diabetes, atherosclerosis or obesity, where this regulation is out of control.

We use different invertebrate and vertebrate tissue culture cell lines as well as the fruit fly Drosophila melanogaster as models to investigate the regulation and mechanisms of cellular and organismic lipid storage. During the last years, we focused on the universal lipid storing organelles, which are called lipid droplets. While present from bacteria to humans, these organelles share a simple and stereotyped structure consisting of a hydrophobic core containing the storage lipids, which is surrounded by a phospholipid hemimembrane with proteins attached. We combined different exploratory high-throughput analyses with in-depth, single gene investigations to learn more about the mechanisms and key players of lipid storage regulation. For example, we identified a large set of proteins associated with the lipid droplets of the fat storing organ of flies, called the fat body, and performed a genome-wide RNAi screen as well as an ultra high-throughput chemical genomics screen (collaboration with the NIH Chemical Genomics Center, Rockville, U.S.A.). Additionally, we characterized identified gene functions in detail such as the fly PERILIPINs.

Currently, we explore the function of identified candidate genes as well as the mechanism-of-action of the identified pharmacologically active compounds. Further, we use focused RNAi screens in combination with automated, multiparametric image analyses to target questions of the cell biology of lipid droplets.

As a new avenue, we started to use the combination of mathematical models and physiological assays to better understand the general design principles of how organisms coordinate their metabolism and growth processes. In combination with the detailed data we gathered so far concerning the cell biology of lipid droplets, this will bring us closer to our long term goal of a better understanding of lipid storage regulation per se and a better understanding of the failed regulation present in human metabolic diseases.

Verantwortlich für den Inhalt: E-Mail sendenDr. Mathias Beller