Lipid Signals in Immunity and Cancer: Insights from Single Molecule Biophysics

Lipid signaling pathways on cell membrane surfaces control a wide array of cell processes in health and disease. These pathways begin with cell surface receptors or intracellular sensors that activate lipid kinase enzymes on the target membrane. The kinases, in turn, generate signaling lipids that diffuse in the membrane plane, recruit downstream signaling proteins, and trigger a cascade of pathway activation and information transfer. My talk will describe our recent studies of three lipid signaling pathways central to immune cell migration, engulfment of pathogens, cell growth and renewal, and oncogenesis. Our approach begins by reconstituting each signaling pathway from purified components on the target membrane. Subsequently, we use tools of single molecule biophysics developed by our lab and others to monitor the membrane-bound signaling proteins and directly measure their 2-dimensional diffusion, interactions, activation, and output lipid signals in real time. This approach provides fundamental new insights that expand our basic understanding of lipid signaling on molecular, dynamic, and mechanistic levels. Such understanding may also facilitate new therapeutics that target defective lipid signaling in autoimmune and inflammatory disorders, and in many human cancers.