Research Interests:
Cells store the majority of their metabolic energy in cytosolic lipid droplets. These endoplasmic reticulum (ER)-derived organelles consist of a core of neutral lipids (mainly triglycerides and sterol-esters), which is uniquely encapsulated by a phospholipid monolayer. Proteins embedded into this membrane include key enzymes for the hydrolysis and synthesis of neutral lipids.
Lipid droplets are highly dynamic organelles that balance influx, storage and consumption of neutral lipids in nearly all cells of our body and are therefore central hubs in lipid metabolism. They are implicated in a range of human pathologies including hallmark diseases of our modern society such as obesity, diabetes, hepatic steatosis and cardiovascular disorders. However, next to nothing is known about the molecular mechanisms underlying protein targeting to lipid droplets, the biogenesis of lipid droplets from the ER membrane and the integration of lipid droplet function into lipid metabolism.
Figure 1: Prevailing Model of Lipid Droplet Biogenesis
Local accumulation of triglycerides (TG) triggers the formation of a lipid droplet (LD) from the cytoplasmic leaflet of the endoplasmic reticulum (ER) membrane, resulting in a phospholipid monolayer-encapsulated LD. The molecular details underlying this process as well as mechanisms that govern the correct targeting and membrane insertion of LD-destined proteins remain enigmatic. Integral membrane proteins on LDs are uniquely embedded into the phospholipid monolayer via hydrophobic hairpin regions and expose all soluble domains towards the cytosol. Some of these hairpin proteins are initially inserted into the ER membrane and partition from the ER to LDs by unknown mechanisms.
Our lab investigates fundamental aspects of lipid droplet biogenesis and function. We recently discovered that lipid droplets share targeting machinery with peroxisomes for some of their membrane protein constituents (Schrul and Kopito, Nature Cell Biology 2016, doi: 10.1038/ncb3373). This suggests that the biogenesis and function of these two organelles with complementary roles in lipid metabolism is coordinated. Projects in our lab currently address three major questions:
- What are the molecular mechanisms underlying protein targeting and insertion into the limiting membrane of lipid droplets?
- How is lipid droplet biogenesis from the ER membrane regulated?
- How do lipid droplets communicate with other lipid metabolizing organelles to adapt to metabolic changes?
We employ a range of biochemical in vitro as well as cell biological approaches in mammalian cells and combine them with advanced light- and electron-microscopy techniques and –omics analyses.
Our long-term goal is to understand how aberrant lipid droplet function contributes to human pathologies such as obesity, diabetes or cardiovascular diseases, which will enable the identification of novel therapeutic targets.
Figure 2: Lipid Droplets are integrated into a functional network of lipid metabolizing organelles
Lipid droplets (LDs) originate from and dynamically exchange proteins with the endoplasmic reticulum (ER) where triglycerides (TG) are synthesized. In addition, they are functionally linked to peroxisomes and mitochondria, where fatty acids (FA) are oxidized. How these organelles cooperate and communicate in order to adapt to metabolic changes needs to be investigated.
Join us!
We are always interested in motivated graduate students and postdocs. If you are interested in joining our young and growing team, please contact me (Diese E-Mail-Adresse ist vor Spambots geschützt! Zur Anzeige muss JavaScript eingeschaltet sein!) with your CV, a statement of research interests and contact information for references. Prospective postdocs should apply early so that financial support through third party funding can be explored.
We also have a number of short-term/thesis projects available for motivated undergraduate students and are looking forward to hearing from you to discuss potential projects.
