Biological Chemistry
Biochemical research in the Chemistry Department is focused primarily on protein structure, nucleic acid chemistry, peptide chemistry and biomodel systems, and bioinorganic chemistry.
Associated Faculty
John Caradonna
Bioinorganic Chemistry and Metallobiochemistry
The Caradonna lab is interested in the biological chemistry of non-heme
iron. Approaches include the investigation of synthetic reactivity models,
biophysical and mechanistic studies of natural metalloenzymes, and the
rational design of metalloproteins.
Sean Elliott
Bioinorganic chemistry and Metallobiochemistry
Protein film voltammetry (PFV) is used in the Elliott lab as a way to
explore the electron transfer pathways and redox-dependent catalytic
chemistry of complex metalloproteins such as sulfite reductase and multicopper
oxidases. We also are devloping proteomic tools to allow us to probe
the 'metallome' -- a complete read-out of the metal-binding components
of biological pathways -- such that we can develop new insight into the
role of metal ions in biochemistry.
Guilford Jones
Pathogen detection using fluorescence bioassays
This work is focused on the development of unique vectors for known sequences
of bacterial genes, including pathogens that are of importance with regard
to biological warfare threats or food and water safety. Fluorescent tagging
of these vectors provides a highly sensitivity method for specific detection
of bacteria.
Signal transduction pathways in human innate-immune responses
The Liu Laboratory research focuses on the interface between chemistry and biology with the emphasis on the chemical basis of pathogen and host interactions, as well as the chemical nature of biological clock. In each project, it divides into two major areas: first, the mechanistic studies of the metallo-proteins in the corresponding process using both biochemical and biophysical methods; second, identification of other components in these two processes using genomic, proteomic and biochemical approaches. The studies in these two projects aim at the long-range goals of developing broad-spectrum antibiotics, elucidating the mechanism of isoprenoid biosynthesis pathway intermediate triggered human innate-immune responses, as well as unraveling the time recording mechanism inside the cell and its relationship to both aging and development.
Organic and medicinal chemistry
In many cases, the fundamental understanding of the function of a biological target enzyme or receptor can be facilitated by development of compounds that selectively bind and stimulate or inhibit function of the target. Our work is focused on applying medicinal chemistry techniques to development of potent and selective compounds that are appropriate for this type of validation. Projects will include pursuit of novel chemotypes that have emerged from the CMLD-BU libraries as biological screening hits, and validation of potential therapeutic targets of relevance to neglected diseases, such as trypanosomiasis.
Scott Mohr
Bioinformatics
Relaxation kinetics in biochemical systems; circular dichroism of proteins
and nucleic acids; psi-DNA; nuclear hormone receptors; bioinformatics.
Thomas Tullius
Biochemistry, Genomics, Bioinformatics
The Tullius laboratory focuses on developing and applying new chemical probe methods for determining the structure of DNA, RNA, and DNA-protein complexes in solution. Our group introduced the use of the hydroxyl radical as a high-resolution chemical footprinting reagent for nucleic acids. We are using deuterium kinetic isotope experiments to obtain detailed information on the chemical mechanism of oxidative damage to DNA and RNA that is induced by the hydroxyl radical. A major project in the lab seeks to develop a database of hydroxyl radical cleavage patterns of DNA. We are using this large collection of DNA structural data to make structural maps of regions of the human genome that are involved in the regulation of gene expression. A second goal of this project is to work out the rules by which DNA sequence is translated into three-dimensional structure. We will then be in a position to predict the structure of genomic DNA, for example to locate sites of unusual structure that represent “signposts” for protein binding.
Biochemistry and bioorganic chemistry
The Whitty Group research centers around reversible noncovalent interactions involving proteins: how they regulate function in complex biological systems such as whole cells, and how they can be exploited in the development of artificial agonists and antagonists for use as protein or small molecule drugs. Their perspective is primarily quantitative and mechanistic, aiming to understand the macroscopic functional behavior of the system in terms of the structures, properties and interactions of the molecules involved.
Associated Graduate Courses
The following graduate courses in the specialization area of biological chemistry are offered:
GRS CH 612 - Separation Methods in Chemistry and Biochemistry
Prereq: CAS CH 301 or consent of instructor. Methods of chemical separation in chemistry and biochemistry, including gas, high performance liquid, thin layer, ion exchange, size exclusion (gel filtration), affinity chromatography, and electrophoresis. Theory of chromatography, instrumentation, and experimental considerations. Preparative and countercurrent techniques. Three hours lecture. Laursen. 4 cr, 1st sem.
GRS CH 621 - Biochemistry I
Prereq: CAS CH 204, CH 212, or equivalent; graduate status. Introductory biochemistry. Protein structure and folding enzyme mechanisms, kinetics, and allostery; nucleic acid structure; lipids and membrane structure; bioenergetics; vitamins and coenzymes; introduction to intermediary metabolism. Three hours lecture, 4 hours laboratory, 2 hours discussion. Same as GRS BI 621. Lecture and laboratory meet with CAS BI/CH 421. Liu, Tolan. 4 cr, 1st sem.
GRS CH 622 - Biochemistry II
Prereq: GRS CH 621 or equivalent. Polysaccharides, energy storage and recognition; intermediary metabolism; lipid and isoprene metabolism; nitrogen metabolism; nucleotide metabolism; macromolecular biosynthesis with emphasis on metabolism; nucleotide metabolism; macromolecular biosynthesis with emphasis on specificity and fidelity in the mechanisms of RNA, DNA, and proteins synthesis. Three hours lecture, 4 hours laboratory, 2 hours discussion. Same as GRS BI 622. Lecture and laboratory meet with CAS BI/CH 422. Kornberg. 4 cr, 2nd sem.
GRS CH 723 - Physical Chemistry of Biological Macromolecules
Prereq: CAS CH 352, GRS CH 651, CH 652, CH 621, or consent of instructor. Physical properties and structures of proteins and related biological macromolecules. Size and shape of macromolecules; denaturation and cohesive forces in proteins; protein folding methods for studying biological macromolecules in solution and in the crystalline state. Xia. 4 cr, 2nd sem.
GRS CH 724 - Special Topics in Biochemistry
Prereq: GRS CH 621. Detailed analysis of special topics of research in biochemistry. The topics are determined by the instructor depending on interest and expertise. Subjects covered include protein analysis, mechanistic enzymology, nucleic acid research, protein/nucleic acid interactions, and spectroscopic methods. Staff, Tullius, Laursen, Mohr. 4 cr, either sem.