LD_Biogenesis · Identification and characterization of sites of lipid droplet biogenesis in the ER
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-03-01 → 2020-03-14
- EU contribution
- €187,420
- Participants
- 1
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
Identification and characterization of sites of lipid droplet biogenesis in the ER
The main scientific objective of this research project was to elucidate the molecular mechanisms of lipid droplet (LD) biogenesis. LDs are fat storage organelles found in all cell types and plays crucial role in cell physiology and lipid metabolism. Dysregulation of LD homeostasis often results in human pathologies such as obesity, type 2 diabetes, cardiovascular diseases, and lipodystrophy (defects in homeostasis of fat tissue). LDs originate from the endoplasmic reticulum (ER), however relatively little is known about how sites of LD formation are determined, and which proteins/lipids are necessary for the process. Studying how LD biogenesis is regulated has broad implication in deciphering the etiology of lipid-storage related disorders. Therefore, the aim of this research project was to study how and where lipid droplets originate inside the cells. In addition, the overall objective of this research project was to impart training to the recruited researcher, by facilitating transfer of knowledge between the host institution and the recruited researcher, and aiding in his career development.
Data: CORDIS, © European Union
Project objective
Lipid droplets (LDs) are evolutionarily conserved dynamic organelles dedicated to storage of fat. Relatively little is known about the molecular processes that regulate nascent LD formation at specific sites in the endoplasmic reticulum (ER). Understanding LD biogenesis and degradation is crucial for deciphering the pathophysiology of LD storage disorders, like obesity, diabetes type-2, atherosclerosis, and lipodystrophy. The main objective of this project is to precisely map and characterize LD biogenesis sites in the ER using the model eukaryote, S. cerevisiae. One reason so little is known about the earliest stages of LD biogenesis is that until recently we have not had tools to visualize and characterize these sites. However, I have generated a yeast strain in which it is possible to use electron microscopy to image the earliest stages of LD biogenesis. In a recently published study I used this strain to characterize early stages of LD biogenesis and I propose to use this strain to investigate the role of a number of proteins in LD biogenesis by using mutants lacking these proteins. In addition, I have developed the first fluorescent protein marker of sites of nascent LD biogenesis. This new protein will allow me to use fluorescent microscopy to visualize LD biogenesis in live cells and in mutants lacking proteins known to be involved in LD biogenesis. I will also use this protein as a molecular tool to identify proteins and lipids that are enriched at LD biogenesis sites in the ER by performing immuno-purification and mass-spec analyses. The proposed studies will reveal and identify proteins and lipids necessary for the earliest stages of LD biogenesis and will make possible future mechanistic studies of LD biogenesis. My participation in “LD_biogenesis” will broaden my scientific expertise and hone my competences in becoming a successful project investigator.
Original text from CORDIS.
Participants
- UNIVERSITE DE FRIBOURG · FribourgCoordinatorSwitzerland
Links
Data: CORDIS, © European Union