The Hansen lab aims to define the general mechanisms cells use to create dynamic spatial heterogeneity in signaling reactions orchestrated on intracellular membranes. Using supported membrane technology and a variety of fluorescence spectroscopy techniques, we are characterizing how lipid modifying enzymes and other signaling molecules are activated on membrane surfaces. Learning molecular details about individual proteins is the first step towards understanding complex emergent properties, such as spatial pattern formation. Overall, we want to build a systems-level understanding of how membrane proximal signaling reactions are executed in cells and how these processes are perturbed in human disease.

 

The ability of cells to regulate the localization of molecules in both time and space is the hallmark of cellular organization. During polarized cell migration, for example, cell surface receptors relay information across the plasma membrane to control the activation of numerous phosphatidylinositol phosphate (PIP) lipid kinases and phosphatases. This results in the synthesis of PIP lipids at distinct locations across the plasma membrane. By selectively recruiting cytosolic proteins to the plasma membrane, PIP lipids function as master regulators of protein localization and function. Genetic and environmental perturbations that create imbalances between opposing lipid kinase and phosphatase activities can negatively impact signaling networks that ultimately control cell morphogenesis, metabolism, and differentiation.

 

Despite the fundamental importance of PIP lipid kinases and phosphatases in biology, many questions remain unanswered concerning their function. What regulates the strength and duration of PIP lipid synthesis reactions in cells? How are micron length scale asymmetries in PIP lipid composition established and maintained across the intracellular membranes? What mechanisms control the dynamic interplay between PIP lipid synthesis and the actin cytoskeleton? To answer these questions, we are building an interdisciplinary team of scientists that use biochemistry, quantitative cell biology, material science, and theory to define the molecular details of membrane signaling events.

 

To learn more about our future research ambitions and unpublished work, please email Scott Hansen.