We are interested in how the cellular environment affects biomolecular function
The cellular environment displays extreme spatial and temporal heterogeneity even in a single cell. For example, as a cell enters mitosis water uptake increases cellular volume by up to 30%, the cytoskeleton disassembles and reforms causing the cell to round up, and the nuclear membrane breaks down releasing sequestered molecules into the cytoplasm within seconds. The way proteins react to routine (or pathological) changes in the cellular environment remains poorly understood. Our research is currently funded by the NIH (grant R35GM137926) and the NSF (award 2128067).
Proteins are sensitive to changes in their surrounding solution
A molecular-level understanding of how cellular changes affect protein function
Live cell microscopy, biophysical methods (CD, flourescence), and computational modeling
How does disease alter protein function?
A significant amount of energy is spent by our cells to maintain a stable and optimal physical-chemical intracellular environment, a process collectively referred to as homeostasis. Yet in certain situations where the cell’s pathways are systematically reprogrammed, homeostasis can break down, causing a change in cellular pH, osmotic pressure, small molecule concentrations, and even the water contents of cells. Remarkably, this intracellular change, often referred to as metabolic rewiring, is common in many pathological conditions including viral infection and most types of cancer cells. How metabolic rewiring affects proteins, the molecular machines that power nearly all cellular functions, is central to understanding how cancer and other metabolically linked pathologies develop.
Regulation of intrinsically disordered proteins by the cellular environment
The cellular environment is dynamic and heterogeneous in both space and time, and far removed from the idealized buffers commonly used in biochemistry experiments. How proteins function in this environment is a fundamental question in biology that is poorly understood. Especially puzzling are intrinsically disordered proteins, which make up over 30% of the human proteome and play a disproportionately large role in cellular regulation and misregulation. Intrinsically disordered proteins have large surface areas and a low number of intramolecular bonds, making them highly susceptible to changes in solution composition. Why have these proteins evolved to be central hubs and regulators of cellular function when routine cell cycle changes can alter their activity? Our lab aims to understand how disordered proteins function and interact in the complex cellular environment, and how the chemical composition of this environment can act as a master regulator that tunes their function.
Environmental control of the biophysical properties of condensed protein phases
Recently, the ability of proteins to form condensed phases has been shown to be critical for various crucial cellular functions. This tendency for phase separation is modulated by a delicate balance between protein structure and the cellular environment, altering the physical and chemical properties of the condensed phase, and the behavior of the proteins that must function within these phases. We look at how changes in the surrounding solution alter the ability of proteins to form specific, functional, and stable condensates.