The main focus of the Jaqaman Lab is to understand the spatiotemporal organization of receptors in the plasma membrane at the single-molecule level, as a means to elucidate the critical first steps in signal transduction. While much research has focused on the complexity of cytoplasmic and nuclear signaling, there is increasing evidence that cell surface receptors are highly organized within the plasma membrane through networks of inter-molecular interactions of most likely similar complexity.
How this organization is achieved and how it influences transmembrane signal transduction are questions that remain largely unanswered but are of fundamental importance to mammalian physiology and pathophysiology. From a therapeutic standpoint, understanding events occurring at the level of the plasma membrane might aid in the design of therapeutic antibodies that bind cell surface receptors, the most rapidly growing class of new drugs.
We hope to pursue the following questions:
- How do networks of receptor interactions integrate positive and negative signals at the level of the plasma membrane?
- What are the kinetics of signal transduction from ligand to receptor to downstream effector?
- How does the mechanical microenvironment influence receptor organization and signaling?
To address these questions, we take integrative approaches that combine light microscopy experiments, particularly single-molecule and super-resolution imaging, with protein engineering, computer vision, and mathematical modeling. Together, these approaches make it possible to establish functional links between the discrete stochastic behaviors of individual molecules and the continuum deterministic behavior of signal transduction at the cellular scale.