Chemical Biology
at Michigan

This website pertains to those who have a research interest in chemical biology in the Department of Chemistry.
For information on the UM Interdepartmental Ph.D Program in Chemical Biology , please see

Chemical Biology studies the fundamental chemical principles that govern all biological systems. The Chemistry Department at Michigan is home to an exciting multidisciplinary program at the interface between Chemistry and Biology. Synthesis, measurement, and theory of biological molecules (including proteins and nucleic acids) are important components of the program. Particular areas of expertise are Metallo-Biochemistry, Biological Catalysis, Biomolecular Structure & Function, Chemical Genetics & Bioorganic Chemistry, and Chemical Imaging & Sensors. Laboratory rotations of choice allow students to explore their individual areas of interest before choosing their thesis mentor. Students may also participate in the unique and NIH funded Chemistry Biology Interface Training Program of the University that spans the departments of Chemistry, Biological Chemistry, and Medicinal Chemistry.

It is estimated that one-third of all proteins are metalloproteins (proteins containing a tightly bound metal ion). Metallo-Biochemistry explores the roles of metal ions in biological samples. At Michigan, interests range from the synthesis of small-molecule mimics for the active sites in enzymes to the structural, spectroscopic, and enzymologic characterization of metal sites in proteins and nucleic acids. A central theme guiding these studies is the effort to relate metal-ion structure and reactivity to biological function.

Rapid-freeze-quench EXAFS analysis of ferritin intermediates (left)
suggests a specific Fe core structure (right; Hwang et al. (2000) Science 287, 122)

Biological Catalysis

Understanding how nature catalyzes the innumerable chemical reactions that occur in living organisms is a problem central to the field of chemical biology. Several research groups are using combinations of physical, chemical, and genetic approaches to investigate the reaction mechanisms of both protein and RNA enzymes. Members of the department are studying a wide range of biologically important chemical reactions, including the modification of proteins by lipid and carbohydrate groups, the generation of free radicals by enzymes, and how RNA molecules are specifically cleaved and processed in the cell.

Radical catalysis: rearrangement of hydroxyglutarate to methylmalate - a novel B12 dependent reaction catalyzed by glutamate mutase (Roymoulik et al. (2000) Biochemistry, in press)

Biomolecular Structure & Function

Biological macromolecules, including proteins (globular and membrane-associated) and nucleic acids, have precise three-dimensional structures that are essential determinants of their biological function. The exploration of the relationship between structure and function is key to understanding the chemical reactivity and molecular recognition properties of biological molecules. At Michigan, interests include: determination of the high resolution structure of macromolecules using NMR, other spectroscopic and crystallographic methods; investigation of the molecular determinants of catalytic activity and molecular recognition; experimental and theoretical studies of the folding of macromolecules into functional structures, and prediction of these structures; and exploitation of macromolecules for the development of therapeutic agents, biomaterials, and biosensors.

De-novo designed synthetic peptides self-assemble to form an a-helical bundle that binds Hg(II) in a cysteine-rich coordination environment (Dieckmann et al. (1998) J. Mol. Biol. 280, 897)

Two distinct conformers in the folding pathway of an RNA enzyme can be resolved by time-resolved fluorescence resonance energy transfer (tr-FRET; Walter et al. (1999) Nat. Struct. Biol. 6, 544)

Theoretical model for the folding pathway of a biomolecule
into a minimum-energy structure

Chemical Genetics & Bioorganic Chemistry

In these areas, cell permeable compounds are used as molecular probes to study intracellular processes. Natural products often provide lead structures as the starting points for these agents. At Michigan, compounds with exquisite specificity for the treatment of genetic and tropical parasitic diseases have been obtained through the use of both rational design and combinatorial chemistry.

Chemical Imaging & Sensors

Imaging and sensing molecules is a central problem in areas ranging from the environmental to the biomedical sciences. Spatial mapping, in real time, of chemical events on the molecular to cellular levels requires fast, sensitive, selective, and non-invasive imaging. State-of-the-art micro-spectroscopic techniques and sensor ensembles are a hallmark of research at Michigan. Researchers at the Chemistry Department, in collaboration with the Medical School, the School of Public Health, and the School of Engineering, are pioneering the design and synthesis of ultra-small devices for the detection of minute amounts of clinically relevant pathogens to diagnose and treat diseases. On a more fundamental basis, the chemical properties of single biomolecules are studied.

A fiber-optic chemical sensor measures the intracellular pH of a red blood cell (Song et al. (1997) Anal. Chem. 69, 863)

The University of Michigan and Ann Arbor

The University of Michigan offers a rich intellectual environment. Opportunities for research collaborations outside chemistry are enhanced by other top-ranked programs in medicine, engineering, physics, applied physics, biology, mathematics, and computer science. The many institutes, laboratories, collections, museums, centers, and libraries provide excellent facilities in a wide range of academic endeavors. Resulting from the strength of its many research programs, the University is currently ranked second in overall research funding in the nation. The University is located in Ann Arbor, a small city of 110,000 which combines the comfort and charm of a college town with the vivid cultural life of a large city.

Faculty Participants

How to Apply
For questions regarding Graduate admission, please contact:
Department of Chemistry,
Phone: (734) 764-7278
FAX: (734) 647-4865

Chemical Biology Doctoral Program
Justine Altman, Program Manager
930 N. University Avenue
1500M Chemistry Building
Ann Arbor, MI 48109-1055
Phone: 734.763.7175
Fax: 734.615.1252

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Chemistry Department, College of LS&A, University of Michigan
930 N. University, Ann Arbor, MI 48109-1055
Email:; Phone: (734) 763-6148; Fax: (734) 647-4865