Graduate students in Biochemistry and Chemical Biology meld molecular and structural biology with physical, organic and analytical chemistry to understand the molecular basis of life. Research in the Biochemistry and Chemical Biology Division focuses on protein, membrane, DNA, RNA and virus function and structure.
Students are a constant source of new hypotheses for mechanisms underlying cellular machines like the ribosome and spliceosome, and for the protein and RNA folding problems. Students tackle these problems using chemical biosensor technologies, protein and nucleic acid crystallography, multi-dimensional NMR spectroscopy, surface chemistry, atomic force microscopy and fluorescence spectroscopy.
Our work also includes major efforts directed towards understanding the molecular basis of disease. Doctoral students leave the Department broadly trained for leadership roles in academia and industry.
All interested students are strongly encouraged to apply via the BBSP program.
Cellular RNA molecules undergo complex folding transitions to form specific, biologically active, three-dimensional structures. A persistent and poorly explained observation is that many RNAs fold very slowly, on timescales requiring minutes or longer. Slow folding ultimately governs the rate at which an RNA can perform its biological function.
In work reported in PNAS, Stefanie Mortimer in the Weeks Lab used time-resolved SHAPE chemistry to show that slow folding at a single nucleotide in the unusual C2'-endo conformation constitutes the rate-determining step for folding a large 50 kDa RNA. Nucleotides in the C2'-endo conformation are relatively rare but are highly overrepresented in functionally critical RNA motifs. This work thus identifies a surprisingly simple, but likely ubiquitous, mechanism for controlling biological processes involving RNA.
Fibrils of the intrinsically disordered protein α-synuclein are hallmarks of Parkinson’s disease. The fluorescent dye thioflavin T is often used to characterize fibrillation, but this assay may not provide quantitative information about structure and mechanism. To gain such information, researchers in the Pielak Group, as reported in the journal Biochemistry, incorporated the 19F-labeled amino acid, 3-fluorotyrosine, into recombinant human α-synuclein at its endogenous tyrosine residues. 19F nuclear magnetic resonance spectroscopy was used to study these labeled α-synucleins.
Although dye binding and 19F NMR data show that 1 mM SDS and 1 mM spermine accelerate aggregation compared to buffer alone, only the NMR data indicate that the species formed in SDS are smaller than those formed in buffer or buffer plus spermine. Thus, 19F NMR spectroscopy can provide quantitative, residue-level, information about protein structure, binding, and fibrillation.