Lipids are key components of cellular membranes playing structural and signalling roles.
Cells also use lipids as an efficient and safe way to store energy.
We use budding yeast as a model organism and a combination of approaches from the fields of Biochemistry, Cell Biology and Genetics to investigate:
how lipid biosynthesis is regulated
how lipid pools are distributed in the cell
how lipid drugs that target cellular membranes impact lipid production, distribution and signalling
Acyltransferase (green) lipid droplet (red)
Journal of Biological Chemistry 287(13):10251-64
Biosynthesis of phosphatidic acid
Phosphatidic acid (PA) represents a key branching point in the biosynthesis of glycerolipids.
Current projects investigate how PA synthesis is regulated at the level of glycerol 3-phosphate acyltransferases. These enzymes are redundant in eukaryotes and we are interested in understanding how different isoforms contribute to different pools of PA, depending on their localization, post-translational modifications and interactions with other proteins.
Phosphatidic acid and diacylglycerol pools
Eukaryotes possess a remarkable diversity of lipid species, varying in acyl chain length and number of double bonds. We are interested in understanding the spatiotemporal regulation of specific pools of phosphatidic acid and diacylglycerol (DAG), which are key lipid precursors and cellular messengers.
We have pioneered the use of a fluorescent probe to monitor DAG pools in live yeast. Current projects aim at identifying novel genes that control DAG distribution using high throughput genomic and imaging approaches.
Diacylglycerol domains (green)
Journal of Biological Chemistry 288(12):8419-32
Targeting cellular membranes by lipid drugs
Metabolically stable lysophosphatidylcholine
derivatives exert antitumor and antiparasitic activities.
We have proposed that upon uptake these lipid drugs target the plasma membrane by altering lipid rafts, therefore affecting the distribution and activity of transporters and proteins participating in signaling cascades.
Current work aims at understanding how these lipids affect the distribution of lipid pools and intracellular membranes using a combination of "omic" approaches in yeast.
Biosynthesis of ether lipids
Ether glycerolipids are abundant lipids in vertebrates and their deficiency is associated with disease in humans. Despite their relevance, our knowledge on the mechanisms that regulate their synthesis and their subcellular distribution is limited. The first acylation step in the synthesis of ether lipids occurs in peroxisomes, and is catalyzed by the enzyme dihydroxyacetone phosphate acyltransferase (DHAPAT). Our work aims at understanding the molecular mechanisms that mediate crosstalk between DHAPAT and non-ether lipid synthesis using yeast as a "test tube". Current focus is on lipid pathway partitioning between endoplasmic reticulum, lipid droplets and peroxisomes.