Energy and Electron Transfer in Photosynthesis Light-driven long-distance electron transfer in photosynthetic reaction centers is one of the fastest known chemical reactions. Recent work addresses four interrelated areas: 1) characterization of membrane organization, domains and protein associations using a novel type of imaging mass spectrometry 2) models for membrane fusion and investigations into the fusion of enveloped viruses to their target membrane 3) development of tethered lipid bilayers as a platform to study membrane domains, junction topology, vesicle fusion and enveloped virus fusion and 4) a membrane interferometer where a free-standing lipid bilayer is held within a few hundred nm of an atomically flat mirror, with the ultimate goal of measuring protein conformational changes optically with sub-nm precision in parallel with electrical measurements, e.g. We have developed methods to partition and manipulate elements of these unique self-assembled systems these methods are now used in many laboratories. A broad vision is to engineer interfaces between hard surfaces and soft materials, ultimately leading to sophisticated biocompatible interfaces that can be used to control, interrogate or organize complex living systems. Model Membranes Our group has developed supported lipid bilayers as mimics for cell surfaces and tools in biotechnology. This has been used to quantify the electrostatic contribution to the catalytic rate in several enzymes. By combining the vibrational Stark effect, vibrational solvatochromism and MD simulations, we have developed a general method to measure the absolute field sensed by the carbonyl probe in proteins. Recent work focuses on carbonyl probes to study enzymatic reactions. These can be used to probe electrostatics and hydration at the active sites of important drug targets. Current work applies nitrile probes introduced into proteins on inhibitors. Vibrational Stark experiments exploit molecular vibrations as local and directional probes to map electrostatic fields in proteins. This led to probes whose sensitivity to electric fields can be calibrated by Stark spectroscopy - spectroscopy in electric fields - which we have developed into a broadly applicable method. Early test systems used mutants of myoglobin, which was first cloned and expressed in our lab. Electrostatics and Dynamics in Proteins We study electrostatics in proteins and how electric fields affect function. Thus these split GFPs are optogenetic elements for manipulations inside cells, and we seek to understand how they work. We have discovered that some split GFPs can be photodissociated, generating a peptide and a truncated protein alternatively, in some conditions, light can be used to associate peptides with truncated proteins. Current work focuses on split GFP in which structural elements such as entire beta strands are replaced with synthetic ones. We and others have since developed this idea to generate novel GFP variants with diverse colors and sensitivities. Our lab was the first to demonstrate that the GFP chromophore exists in two protonation states, interconvertible by ultrafast excited state proton transfer. We are pursuing several interconnected themes: Excited State Dynamics in GFP & Split GFP Green Fluorescent Protein (GFP) is widely used as a probe to localize proteins in cells.
We invent experimental methods and develop theory as needed. My laboratory investigates the structure and function of biological systems with a strong physical perspective. Vice Provost for Undergraduate Education.Office of Vice President for Business Affairs and Chief Financial Officer.Office of VP for University Human Resources.
Stanford Woods Institute for the Environment.Stanford Institute for Economic Policy Research (SIEPR).Institute for Stem Cell Biology and Regenerative Medicine.Institute for Human-Centered Artificial Intelligence (HAI).Institute for Computational and Mathematical Engineering (ICME).