Dr Michael Gryk, Assistant Professor, MMSB*

The focus of our laboratory is the use of NMR spectroscopy as a tool for macromolecular characterization. Our studies currently involve protein and protein-DNA systems of relatively large molecular weight for NMR spectroscopy (20-70 kDa). Current methods to overcome the difficulties inherent in studying these large systems include extensive labeling using stable isotopes and the use of TROSY-based pulse sequences. A critical mission of the lab is the facility approach to NMR, such that as advancements are made, they are tailored for ease-of-use both internally and externally when possible.

Dr Jeffrey C. Hoch, Associate Professor, MMSB* (Director)

Jeff is the one on the right. The Hoch laboratory works on computational aspects of biomolecular NMR spectroscopy, including spectrum analysis and structure computation, and investigates protein structure, dynamics, and stability using NMR and other biophysical methods such as calorimetry and osmometry. His laboratory is also studying water-biomolecule interations via NMR and osmometry. A novel high-precision vapor pressure osmometer is being developed for these studies. Visit the lab web site for additional information.

Dr Stephen M. King, Professor, MMSB*

Dyneins are microtubule-based molecular motors that power both ciliary/flagellar motility and a variety of essential intracellular motile events. In order for these massive enzymes to function correctly, they must be attached to the appropriate cargo and motor activity must be precisely regulated. Over the last few years we have identified a series of highly intriguing dynein components that appear to be involved in these regulatory activities. Current focus in the laboratory is on understanding the mechanisms which control motor function using a wide variety of techniques ranging from physiological measurements and genetic analyses to structural biology. Visit the lab website for more details.

Dr Mark W. Maciejewski, Assistant Professor, MMSB*

Human DNA is insulted by 10,000 to 1 million damage events per living cell per day. DNA repair is therefore critical to the overall stability of the genome and to life itself. The consequences of inefficient DNA repair include cancer, aging, and other diseases. We aim to develop a molecular understanding of the mechanism and, in particular, the high fidelity of DNA repair. To accomplish this we utilize NMR spectroscopy, in conjunction with complementary biochemical, biophysical and molecular biological approaches, to study the three-dimensional structure, dynamics, and interactions of DNA repair proteins.

Dr Peter Setlow, Professor, MMSB*

Dormant spores of Bacillus and Clostridium species are much more resistant to a variety of harsh treatments than their growing cell counterparts. This extreme resistance makes spores of a number of these species causative agents for food spoilage and food-borne disease, and, in the case of B. anthracis, a candidate for biological warfare. A major factor in spore resistance is protection of spore DNA by the binding of alpha/beta-type small acid-soluble spore proteins (SASPs). SASPS undergo a profound structural alteration upon binding DNA. We are using NMR spectroscopy to determine the structure of a SASP-DNA complex in order to understand the precise details of these conformational changes.


Faculty at UConn Storrs Campus

Dr Andrei T. Alexandrescu, Associate Professor, Department of Molecular & Cell Biology

Establishing the rules by which proteins fold remains one of the most important challenges in biology. The principal goal of protein folding studies is to understand how proteins acquire their functional native structures. An intimately connected aspect is the nature of the denatured states of proteins. Denatured states are the starting points of folding reactions, are critical determinants of protein stability, and are increasingly recognized for their importance in disease. Indeed, the current pharmaceutical paradigm could be considerably extended if protein folding were sufficiently well understood to target denatured states. The structure and dynamics of denatured and partially folded proteins are being explored using a variety of NMR probes including spin relaxation, through-hydrogen-bond couplings, and residual dipolar couplings. A second research interest is structural characterization of the molecular components of the neuromuscular junction. Current NMR work is focused on the protein agrin, which has key roles in the development and maintenance of synapses between nerves and muscle.



Former Members

Dr Martin Schiller, Associate Professor, MMSB* (Currently at University of Nevada, Las Vegas)

Axonal outgrowth requires the coordination of many cellular processes including rearrangement of the cytoskeleton, targeted deposition and retrieval of membranes, and synthesis of new membrane and cytoskeletal constituents. Kalirin is a protein that appears to be involved in coordinating several of these processes. In order to elucidate the molecular mechanisms by which kalirin is regulated, and to determine its role in axonal outgrowth, we are using NMR spectroscopy to determine the structure of key kalirin domains and to identify ligand binding sites using chemical shift mapping experiments.

Dr Zheng-yu Peng, Professor, MMSB* (Deceased)

Our lab is interested in understanding the mechanisms of protein folding, macromolecular recognition, and the structural consequences of mutations that result in protein misfolding and human disease. We are currently studying the structure, folding, and design of ankyrin repeat proteins, which play important roles in signal transduction, transcriptional regulation, tumorigenesis, and inflammatory and immune responses. Students entering the lab will have the opportunity to learn a variety of biophysical, computational, and protein chemistry techniques.

Dr Glenn F. King, Professor, MMSB* (Currently at University of Queensland, Brisbane, Australia)

During vegetative growth, most bacteria form a division septum at the center of the cell by coordinated ingrowth of the cytoplasmic membrane, the rigid peptidoglycan layer, and, in the case of Gram negative bacteria, the outer membrane of the cell envelope. In order to better understand this complex event, we are using NMR to study the structure and interactions of proteins involved in the septation process, as well as those involved in timing and placement of the division septum. We are also using NMR to study structure-function relationships in several families of insecticidal neurotoxins that were discovered in the lab and which we plan to develop as insect control agents.

Dr Philip Yeagle, Professor and Chairman, Department of Molecular & Cell Biology, Storrs Campus (Currently at Rutgers, Newark)

Current research efforts are focused on the unsolved problem of membrane protein structure. We have developed a new segmented NMR approach to the structure of membrane proteins and have used it to successfully solve three dimensional structures at medium resolution for bacteriorhodopsin and the dark-adapted state of bovine rhodopsin. These structures agree well with those determined using X-ray crystallography. Most recently we have used this method to obtain a structure for metarhodopsin II, a transient activated state of rhodopsin. This is the first structure for an activated G-protein coupled receptor.


MMSB = Molecular, Microbial, and Structural Biology