The Mysterious Lipid Signal
Lipids are water-repellant molecules that, in biological systems, can act as energy stores, major constituents of cellular membranes, and intracellular signaling molecules. In the latter capacity, signaling lipids such as phosphatidic acid function as second messengers that cause cells to change their metabolism, gene expression, and behavior in response to diverse extracellular stimuli. Phosphatidic acid can, depending on the context, initiate cell growth and proliferation, promote cell migration, and increase protein secretion. It remains a mystery how one lipid signal can cause such diverse physiological events. The main impediment to dissecting the roles of phosphatidic acid is a lack of tools to visualize and modulate its production with spatiotemporal control.
With this CAREER award, Jeremy M. Baskin, Chemistry and Chemical Biology, is developing chemical probes to study the phosphatidic acid-mediated signaling pathways that are vital to human health and wellbeing. Baskin’s group is using chemical and biochemical tools to report on and control phosphatidic acid synthesis and to study an important signaling pathway thought to be under the control of this lipid.
The new tools include a chemical method to image intracellular sites of phosphatidic acid production within live cells and a chemoenzymatic strategy to enable production of phosphatidic acid on demand at precise locations within live cells. Baskin’s group will then apply these tools to probe mechanistic questions about the role of phosphatidic acid in orchestrating cell growth pathways.
This work will generate new methodologies for studying lipid signaling and fundamental knowledge into how a single lipid signaling agent can direct precise cellular signaling outcomes.