Charles G. Hoogstraten
Assistant Professor
- B.S. 1990, Michigan State University, Chemistry & Biochemistry
- Howard Hughes Medical Institute Predoctoral Fellowship, 1990-1995
- Ph.D. 1995, University of Wisconsin - Madison
- Helen Hay Whitney Postdoctoral Fellow, 1995-1998, University of Colorado, Boulder
- Visiting Postdoctoral Fellow/Junior Research Specialist, 1998-2002, UC Davis, Chemistry
hoogstr3@msu.edu
302D Biochemistry Building
Michigan State University
East Lansing, MI 48824-1319
Office: 517-353-3978
FAX: 517-353-9334
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Charles G. Hoogstraten Research Interests
The Hoogstraten laboratory studies biologically and biochemically important problems using techniques derived from biophysics and physical chemistry. Specifically, we are interested in the structure and function of RNA as studied using high-resolution nuclear magnetic resonance spectroscopy (NMR) in the liquid state, contemporary electron paramagnetic resonance (EPR) spectroscopy, and other techniques including solution thermodynamics.
One major area of interest is the study of the relationships between conformational dynamics, metal ion cofactors, and the catalytic mechanisms of catalytic RNA molecules (ribozymes). Solution-state NMR is unparalleled in its ability to give comprehensive site-specific information on the extent and timescales of dynamics of internal motions in macromolecules. We are interested in novel schemes to use this information to pick apart theconformational transitions that are a key part of the reaction coordinate for many ribozymes. Comparisons of NMR data with kinetic studies of ribozyme variants, or "dynamics-function" studies, provide particular insight into mechanism. As polyanions, catalytic RNA molecules often require divalent metal cation cofactors, which can play either structural or functional roles. We complement the NMR studies by using pulsed EPR to determine the structure of such metal ion sites in ribozymes and other RNA molecules.
A second major focus is the protein-RNA recognition events that are important in the regulation of alternative pre-mRNA splicing in eukaryotes. Alternative splicing is emerging as a major contributor to the regulation of gene expression, and also plays a dominant role in generating diversity in the proteome, which can exceed the diversity of the genome by orders of magnitude. Sequences in the pre-mRNA exons and introns can either favor or disfavor the usage of nearby splice sites when recognized by modular RNA-binding proteins of the SR family. SR proteins are modular molecules whose RNA-binding affinity and specificity emerge in a nonlinear way from the characteristics of individual RNA-binding domains. We will use a combination of NMR studies of domain orientation and ligand-induced folding, EPR in combination with site-directed spin labeling for studies of global interdomain structure, and solution thermodynamics using isothermal titration calorimetry (ITC) to unravel the physicochemical bases of this key RNA-protein recognition event.