Fat storage heterogeneity

The project aimed to investigate the heterogeneity of fat storage organelles, focusing on the peri-lipid droplet (peri-LD) cage, using proteomic and functional assays in C. elegans and mammalian cells. Prior research revealed lipid droplets as primary organelles for fat storage in eukaryotic cells, containing triglycerides (TAG) and cholesterol esters (CE) surrounded by a phospholipid monolayer. The lab aimed to understand fat storage regulation at the endoplasmic reticulum (ER) - lipid droplet interface, finding that coupling involved a macro-molecular complex. They discovered two lipid droplet populations, one marked by Seipin, mutations of which caused congenital generalised lipodystrophy, leading to severe metabolic defects. The project generated transgenic worms and mammalian cell lines expressing Seipin. The main objectives of this project included elucidating peri-LD cage proteomes, validating candidate protein localisation, and performing functional analysis using CRISPR-mediated genome editing to provide insights into cellular lipid homeostasis and its disruption in metabolic diseases.