Mark Rould graduated summa cum laude from the University of Arizona with a double BS in Biochemistry (with Honors) and Cellular and Developmental Biology. He recieved his PhD in 1991 from Yale University, solving the first crystal structure of an aminoacyl-tRNA synthetase bound to its cognate tRNA, in the laboratory of Prof. T.A. Steitz. During his postdoctoral period with Professor Carl Pabo at MIT, he participated in the crystallographic determination of more than a dozen macromolecular structures, primarily protein-DNA complexes. Mark came to UVM in 1998 to create the UVM Center for X-ray Crystallography and serve as its director.

Research Interests

Understanding how molecules small and large are recognized by proteins, and how their binding can elicit changes in protein structure, is the central theme tying the broad spectrum of projects pursued in our lab. We forge and wield new tools in the field of X-Ray Crystallography to decipher the molecular basis of natural and exogenous ligand binding, and the propagation of conformational change. For example, collaborative projects with Kathy Trybus and Susan Lowey are aimed at visualizing the pathway by which changes in the nucleotide state of motor proteins such as kinesin, myosin and actin are coupled to the conformational changes ultimately responsible for directed biological motion. Visualizing at atomic resolution the molecular choreography involved in DNA recombination and DNA repair are also key collaborative projects with Scott Morrical, Sylvie Doublie and Susan Wallace. In collaboration with UVM chemist Jose Madalengoitia, we have developed and are applying a high-throughput crystallographic approach to detect and characterize protein-ligand interactions from within extensively diverse combinatorial libraries of organic compounds, as a means to accelerate the search for pharmaceutical leads.

Towards Direct Pharmaceutical Control of Gene Expression: Exogenous ligand bound to the DNA-binding surface of a transcription factor

Molecular Motors in Motion: Crystallographic stereo-snapshot of the two-stroke actin motor

Selected Publications

Rould, M.A., Carter, C.W. Jr. (2003) Isomorphous Difference Methods Methods in Enzymology 374, 145-163

Xu, H., Beernink, H.T.H., Rould, M.A., Morrical, S.W. (2006) Crystallization and preliminary X-ray analysis of bacteriophage T4 UvsY recombination mediator protein Acta Cryst F62, 1013-1015

Wally, J., Halbrooks, P.J., Vonrhein, C., Rould, M.A., Everse, S.J., Mason, A.B., Buchanan, S.K. (2006) The crystal structure of iron-free human serum transferrin provides insight into inter-lobe communication and receptor binding J. Biol. Chem. 281, 24934-44

Rould M.A, Wan Q., Joel P.B., Lowey S., Trybus K.M. (2006) Crystal Structures of Expressed Non-polymerizable Monomeric Actin in the ADP and ATP States J Biol Chem,in press [Epub:doi:10.1074/jbc.M601973200]

Rould M.A. (2006) The Same but Different: Isomorphous Methods for Phasing and High-Throughput Ligand Screening Methods in Molecular Biology, in press

CMB Lab Members