Biophysical Methods:

While all participating faculty apply biophysical methods to biological questions, some of the faculty also work on development of methods.

Rieko Ishima, NMR spectroscopy
Judith Klein-Seetharaman , Fluorine NMR spectroscopy for membrane proteins
Angela Gronenborn, NMR spectroscopy
Joanne Yeh, X-ray crystallography methods including in-situ annealing, rational crystallization methods
James Conway, Cryoelectron microscopy
Peijun Zhang, Cryoelectron microscopy
Guillermo Calero, X-ray crystallography, dynamic light scattering
Patrick van der Wel, Solid state NMR spectroscopy

Gene Regulation & Signaling:

Gene regulation and signaling are fundamental biological processes of interest to many participating faculty.

Judith Klein-Seetharaman, Mechanisms of signal transduction by membrane receptors
Peijun Zhang, Mechanisms of signal transduction by membrane receptors
Angela Gronenborn, Structural basis of signaling & gene regulation by NMR
Guillermo Calero, Structural and biochemical studies of the transcriptional machinery (RNA PolII and the general transcription factors)

Lipid Structure & Protein Interactions:

Lipid membranes are among the most ubiquitous cellular structure among organisms. Understanding how lipids achieve its structural and chemical integrity remains an area of active investigation. Research in this area examines lipids from a structural and functional perspective. Interactions between lipids and proteins are crucial and serves to stabilize, functionalize, and regulate membrane and peripherally-associated proteins.

Judith Klein-Seetharaman, Lipid-induced conformational changes in membrane proteins
Joanne Yeh, Crystal Structure and Biophysical Characterization of Membrane Proteins
Patrick van der Wel, Structural and biophysical characterization of protein-lipid interactions by solid state NMR

Macromolecular Recognition:

Research in this area is focused on elucidating the mechanisms of interactions between molecules – enzyme-substrate, protein-DNA, and protein-ligand. These studies focus on detailed characterization of the exquisite specificity between molecules and how this is achieved, from the point of recognition to attaining high affinity. Additional studies focus on mechanisms by which reactions proceed, from a structural perspective.

Angela Gronenborn, Structure, dynamics and energetics of protein-carbohydrate interactions
Judith Klein-Seetharaman, Membrane receptor - protein interactions
Joanne Yeh, Protein-Protein Interactions between Membrane Channels and Proteins and Signaling Partners

Principles of Protein Structure & Dynamics:

Structural biology is undergoing a quiet revolution. Despite the thousands of high resolution – but static – protein structures now available in the Protein Data Bank, scientists have broadly recognized that many biochemical questions about these proteins remain open. The reason is simple. By and large, proteins are machines that perform their jobs by moving – rendering a static view incomplete. Using both experimental and computational approaches, a number of the training faculty have turned their attention to the study of fluctuations and dynamics in biomolecules. Techniques include NMR, Raman spectroscopy, coarse-grained computational modeling and other advanced molecular simulation approaches.

Angela Gronenborn, Structural basis of signaling & gene regulations
Judith Klein-Seetharaman , Mapping of sequence to structure, dynamics and function of proteins
Pei Tang, NMR & computations of protein structures, dynamics & drug effects
Patrick van der Wel, Characterization of structure and formation of amyloid fibrils by solid state NMR

Structure & Dynamics of Membrane Proteins:

Research in this area involves structural, biochemical, and pharmacological characterization of integral membrane proteins. The major objectives of these studies are to determine the mechanism by which these critical proteins function in the context of the lipid membrane, which serves both as a barrier and a unique environment. These studies address questions pertinent to fundamental biology: how is a signal is transduced across the membrane; how is selectivity and high permeation maintained by a membrane channel; what are the mechanisms to regulate the activity of the membrane protein? To address these questions, advanced modern approaches of X-ray crystallography, NMR, electron microscopy, and computational analysis are used.

Judith Klein-Seetharaman, Conformational dynamics in membrane receptors
Peijun Zhang, High-resolution cryo-electron microscopy of macromolecular assemblies
Joanne Yeh, X-ray crystal structures and functional studies of membrane receptors and channels
Pei Tang, NMR & computations of membrane protein structures, dynamics & drug effects
Yan Xu, NMR of ion channels & low-affinity drug action
Guillermo Calero, Structural and biochemical studies of membrane signaling pathways
Patrick van der Wel, Structural and biophysical characterization of protein-lipid interactions by solid state NMR

Virus Protein Structure:

Virus structure, assembly, function and evolution is investigated by a growing group of researchers.

James Conway, Virus structure with cryo-electron microscopy
Judith Klein-Seetharaman, HIV-glycoprotein 41 transmembrance structure, dynamics and interactions
Angela Groneborn, HIV proteins and their interactions
Rieko Ishima, HIV protease