CAREER: Investigating how proteins and lipids coordinate the formation and function of membrane-associated condensates

This research will lead to a better understanding of how the cell surface is organized, which could lead to breakthroughs in developing biotechnology, treating diseases, and improving our overall understanding of how cells communicate and function. This project exploring how cells carefully organize proteins and lipids on cell surfaces will advance biological discovery and have a broader impact on biology education. For undergraduates, this project will enrich the existing curriculum by offering undergraduate students an opportunity to participate in the research. This research will also support the training of graduate students, providing hands-on experience in cutting-edge techniques and critical thinking skills, and preparing them for careers in academia, industry, and beyond. This project will also support a brand-new initiative to teach cell biology educators about emerging topics related to our research. In the past decade, scientists have begun to appreciate an important mechanism of sub-cellular organization, the formation of membrane-less “biomolecular condensates” through liquid-liquid phase separation. The goal of this project is to understand how protein and lipid molecules coordinate the formation and function of condensates at the plasma membrane. The research will use biochemical reconstitutions of condensates to understand how phosphoinositide lipids and adaptor proteins function together to regulate signaling. Although phosphoinositide lipids are a minor component of cellular membranes, they play a central role in regulating membrane form, function, and dynamics within cells. The specific aims of this project are to determine the impact of membrane phosphoinositide content on condensate formation, size, composition, and function; determine how the recruitment of specific adaptor proteins impacts local phosphoinositide lipid composition within condensates; and determine how specific protein enzymes control local phosphoinsitide lipid composition within condensates. This research will reveal fundamental mechanisms by which proteins and lipids may coordinate the formation and function of membrane-associated condensates throughout the cell. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.