Structural and Computational Biology Research


Structural and Computational Biology. Several of our research groups are using X-ray crystallography, cryo-EM, NMR, EPR, and other biophysical techniques to reveal the functions and cellular mechanisms of diverse proteins, nucleic acids, macromolecular assemblies, and disease-related molecules. Studies aimed at elucidating biological phenomena are supported by technical developments aimed at advancing the current limits of structural biology methods. Our structurally-oriented research programs are strongly complimented by diverse studies in computational and synthetic biology. These range from algorithmic developments in the areas of bioinformatics and genomics to macromolecular structure prediction and design.


 

Faculty Research Summaries

James U. Bowie

James U. Bowie

Professor James Bowie and his group are fascinated by protein structure, folding and stabilization. This interest has led them into three main areas: (1) learning how membrane proteins fold and how they can be stabilized; (2) the structures and biological functions of a biological polymer they discovered, that is formed by a very common protein module called a SAM domain; (3) developing and stabilizing enzyme pathways for the production of biofuels.

Catherine F. Clarke

Catherine F. Clarke

Professor Catherine Clarke and the Clarke lab study the biosynthesis and functional roles of coenzyme Q (ubiquinone or Q). Q functions in mitochondrial respiratory electron transport and as a lipid soluble antioxidant. The group is using the yeast Saccharomyces cerevisiae (bakers yeast) to elucidate the biosynthetic metabolism of Q. Their experimental approach employs a combination of molecular genetics, lipid chemistry and biochemistry to delineate the steps responsible for Q biosynthesis.

Robert T. Clubb

Robert T. Clubb

Professor Robert Clubb investigates the molecular basis of bacterial pathogenesis. In particular, his group studies how microbes display and assemble cell wall attached surface proteins, and how they acquire essential nutrients from their host during infections. The group's study could lead to creating new inhibitors of bacterial infections.

 

David S. Eisenberg

David S. Eisenberg

Professor David Eisenberg and his research group focus on protein interactions. In their experiments they study the structural basis for conversion of normal proteins to the amyloid state and conversion of prions to the infectious state. In bioinformatic work, they derive information on protein interactions from genomic and proteomic data, and design inhibitors of amyloid toxicity.

 

Juli Feigon

Professor Juli Feigon and her research group study nucleic acid structure and specific recognition of nucleic acids by proteins. Her group focuses on determining the three-dimensional structures of DNA and RNA, and on investigating their interactions with various proteins and ligands, and to study nucleic acid folding.

 

William M. Gelbart

The Gelbart Lab is fascinated by the structural and mechanical properties of viruses- the complex structure and self-assembly of these nanoscale devices in detail provides a problem that is simultaneously at the forefront of statistical mechanics and the life sciences.

 

Wayne L. Hubbell

Dr. Hubbell's research is focused on understanding the relationship between the molecular structure of a protein and the conformational changes that control its function. Of particular interest are membrane proteins that behave as "molecular switches", i.e., proteins whose structures are switched to an active state by a physical or chemical signal.

 

Kosuri

Sri Kosuri

The Kosuri laboratory develops and combines three recent technologies: DNA synthesis, DNA sequencing, and genome engineering. First, the lab develop methods to build large libraries of synthetic DNA sequences using low-cost DNA microarrays. This allows them to build thousands to millions of designed constructs for modest cost. Second, they develop new measurement technologies using next-generation sequencing that allows the lab to test the functionality of these synthetic DNA libraries simultaneously. Finally, using new genomic engineering technologies, the Kosuri lab can do these large-scale synthesis/sequencing experiments in a wide-variety of cell types and organisms. 
 

Christopher J. Lee

Professor Christopher Lee's main area of research is in bioinformatics. His group studies 1) analysis of alternative splicing and genome evolution, 2) analysis of protein evolutionary pathways, and 3) development of a general framework for working with genomic data as an abstract graph database.

 

Joseph A. Loo

The research interests of Professor Loo's group include the development and application of bioanalytical methods for the structural characterization of proteins and post-translational modificationsproteomics-based research, and the elucidation of of disease. The composition and structure of noncovalently-bound protein-protein and protein-ligand interactions are studied by electrospray ionization mass spectrometry and ion mobility.

 

Heather D. Maynard

The Maynard group focuses on polymer chemistry and nano medicine. We design and synthesize polymeric mimics of natural molecules with the purpose of stabilizing proteins and siRNA. These materials are applied to wound healing, diabetes, and for the treatment of cancer. We also prepare polymers for conjugation of proteins to surfaces in specific orientations for diagnostics and biomaterials that control cell behavior.

 

Margot E. Quinlan

Professor Margot Quinlan and her group use biochemistry, microscopy and genetic approaches to study regulation of the actin cytoskeleton. The group is currently focused on Spire (Spir) and Cappuccino (Capu), two proteins that collaborate to build an actin network essential for early body axis development. Combining an in vitro understanding of the mechanism of Spir and Capu with in vivo studies of polar cells will provide insight into how the actin cytoskeleton is regulated and a broader understanding of cell polarity.

Emil Reisler

Professor Emil Reisler and his group investigate cell motility and force generation mechanism of actin, tubulin, and a family of motor proteins. The aim of these studies is to obtain a structural description of the mechanism of motion and force generation. At the cellular level, the group studies the function, interactions, and structural transitions of the assembled protein systems.

 

Jose Rodriguez

Prof. Rodriguez studies the complex architecture of biological systems - from single biomolecules to cellular assemblies - at high resolution. His work is largely based on diffraction phenomena and combines computational, biochemical and biophysical experiments. The development of new methods is central to this work, particularly using emerging technologies in cryo-electron microscopy, nano and coherent x-ray diffraction, and macromolecular design. Combined, these tools can reveal undiscovered structures that broadly influence chemistry, biology, and medicine.

Alexander Spokoyny

Research in the Spokoyny laboratory is devoted towards establishing new synthetic avenues, structural understanding, and applications for inorganic and organomimetic clusters. These efforts will reveal novel and potentially useful solutions to important problems in the field, including: catalysis, energy storage and selective recognition and labeling of biomolecules.

 

Todd Yeates

In the area of structural biology, the Yeates lab's emphasis is on supra-molecular protein assemblies. Much of the lab's recent work has focused on bacterial microcompartments -- extraordinary protein assemblies comprised of thousands of subunits reminiscent of viral capsids. These assemblies encapsulate a series of enzymes within a protein shell, which controls the transport of substrates and products into and out of the microcompartment interior and serve as primitive metabolic organelles in many bacteria. The lab's structural studies on these systems provided the first three-dimensional views of the shell proteins, and have generated long-needed mechanistic hypotheses for how bacterial microcompartments function.