50 Characterizing the regulatory circuitry of global lipid metabolism.

Project: Research

Project Details


The lipidome of eukaryotic cells comprises hundreds to thousands of molecular lipid
species that constitute and functionalize biomembranes, store metabolic energy in
lipid droplets, and function as signaling molecules that control cell and organism
physiology. The mechanisms of how cells regulate lipid metabolism on a
lipidome-wide level and sustain lipid homeostasis remain poorly understood.
Notably, dysfunctional lipid homeostasis is known to cause cellular lipotoxity and
precipitate disorders such as obesity, atherosclerosis and neurodegeneration (3).
Recent studies, including work by the applicant and collaborators, support the notion
that the lipid metabolic network of cells is dynamically regulated by protein
phosphorylation. Moreover, the regulatory circuitry of global lipid metabolism
appears to utilize conserved signaling pathways to transmit signals via protein
kinases and phosphatases to modulate the dynamics of lipid metabolism and to
sustain lipid homeostasis. To identify the constituents of this multi-component
regulatory circuitry and delineate its operational principles requires technology that
affords reproducible, comprehensive and quantitative monitoring of dynamic
changes in lipid enzymes, regulatory proteins and molecular lipid species. The aims
of this research program are to develop a mass spectrometry-based proteolipidomics
platform that enables systems biology studies of lipid metabolism and to characterize
the regulatory factors that mediate global lipid homeostasis.
Effective start/end date01/01/201431/12/2019