Research Projects

The plasma membrane (PM) of eukaryotic cells regulates numerous cellular functions ranging from protecting cells from noisy environment to orchestrating biochemical processes underlying homeostasis. Dynamic interactions among the lipids and other constituents of the PM yield a heterogeneous two-dimensional (2D) fluid exhibiting lateral liquid-liquid phase separation (LLPS) into co-existing liquid ordered (Lo) and liquid disordered (Ld) phases or domains. The Lo domains are hypothesized to be ‘hotspots' of cellular signaling reactions, membrane trafficking, and virus entry. Likewise, cytosolic proteins may also undergo dynamic phase separation into co-existing protein-rich ordered condensate and protein-dilute disordered phases. However, the physico-chemical origin and biophysical characteristics of these ordered features (Lo domains and condensates) in live cells remained hotly debated due to their transience and nanoscopic size. In this project, we will combine synthetic and molecular biology with advanced fluorescence microscopy and spectroscopy techniques to systematically derive physico-chemical principles underlying PM phase separation. The functional relevance of PM phase separation will be investigated in antigen-mediated signaling of immunoglobulin E (E) receptor Fc?RI, which is considered a general paradigm of transmembrane signaling, in live cells. In parallel, we aim to integrate the principles of PM (lipid-based) and cytosolic (protein-based) phase separation in physiologically relevant cellular processes starting at the PM and propagating through cytosol for eventual biological response. Overall, the research proposal aims to discover fundamental principles of functional membrane heterogeneity and its association in signal transduction.