CBI Trainees

CBI trainees come to Illinois from highly regarded undergraduate programs, nationwide. Regardless of their undergraduate majors, they have in common the potential to perform cutting-edge discipline-spanning work at the interface of chemistry and biology.

2005-2007 Trainees	Home Department	CBI Mentor
Alexis Black Research Project Description: Transfer RNAs are the key to ensuring that the translation mechanism works smoothly and keeping the genetic code intact during protein synthesis. The aminoacyl synthetases charge tRNAs with the correct amino acid which is added to the growing polypeptide chain at the ribosome. The binding of the tRNA to the synthetase has been studied statically, but there are still many questions about how the tRNA is recognized by its cognate synthetase. Using bioinformatics and state of the art molecular dynamics simulation, I am studying the binding of the tRNAAsp to the Asp-aminoacyl synthetase according to interactions between the anticodon loop of the tRNA and the anticodon binding domain of the synthetase. This will hopefully lead to finding the physical pathway by which tRNA is recognized and bound to the synthetase.	Chemistry (Chemical Biology)	Zaida Luthey-Schulten
Ben Circello Research Project Description: My research focuses on the isolation and characterization of phosphonate biosynthetic gene clusters. In order to identify these clusters in organisms available sequence data was used to construct a series of degenerate PCR primers which act as probes. Environmental soil isolates were considered a large possible reservoir and were screened using these primers. A large number of positives was obtained (~65). Of these, several are being examined further using phosphorus NMR and cosmid library construction.	Microbiology	William Metcalf
Lisa Cooper Research Project Description: Lantibiotics are a unique class of antibiotics made up of ribosomally synthesized and post-translationally modified peptides. My project has focused primarily on lacticin 481, a type AII lantibiotic produced by Lactococcus lactis CNRZ 481. I have explored the role of the leader peptide using site-directed mutagenesis of highly conserved residues in the sequence near the proteolytic cleavage site. I am also analyzing the substrate specificity of LctM, the dehydratase and cyclase enzyme for lacticin 418, by examining the specificity for amino acid residues in close proximity to the dehydrated serines and threonines. My second project is the mechanistic interrogation of the biosynthesis of cinnamycin, a type B lantibiotic produced by Streptomyces cinnamoneus cinnamoneus. The most immediate goals include reconstitution of CinM activity in vitro, site-directed mutagenesis studies, and crystallographic structural determination.	Biochemistry	Wilfred van der Donk
Jill Gunther Research Project Description: Carbonic Anhydrase 12 is a membrane-associated enzyme that regulates cellular pH and is present in both breast and prostate tumors. Because CA12 is a primary response gene under regulation by estrogen, it should act as a reliable monitor of estrogen receptor function within these tumors. I am refining an assay to test the binding affinities of fluorine-substituted CA12 inhibitors and working to express and purify this protein. In vivo imaging of these tumors by positron-emission tomography (PET) using these inhibitors in fluorine-18 labeled form, before and after a hormone challenge, should report on the functionality of estrogen receptor action and, therefore, be predictive of effectiveness of hormone therapy in the treatment of these cancers. I am also examining classes of ER subtype-selective ligands that show much higher selectivity in terms of transcriptional potency (EC50 values) than in terms of binding affinities (Ki values). I am using coactivator-interaction assays to investigate whether these difference reflect error in assay or significant subtype discrimination at the level of the interaction of the ER-ligand complex with coactivators.	Chemistry (Chemical Biology) Medical Scholars Program	John Katzenellebogen
John Rakus Research Project Description: Uncovering functional diversity within the enolase superfamily and identifying substrate diversity within individual members of the superfamily can give us clues as to how enzymes with nearly universally conserved active site architecture can evolve many disparate functions. To that end my research is somewhat two-pronged. I am attempting to characterize several enolase superfamily members from the soil bacterium Polaromonas sp JS666 which currently have unknown function and unclear genomic context. The GI numbers for these proteins are 67847749, 67910434 and 67928240. Additionally I’m taking a member of known function, rhamnonate dehydratase from Escherichia coli and am attempting to characterize the chemical basis for its mechanism as well as specific interactions involved in this protein’s substrate specificity.	Biochemistry	John Gerlt
Paul Thomas Research Project Description: The coactivator p300 and the estrogen receptor are two of the many regulators of RNA polymerase II mediated transcription through direct and indirect histone modifications. While p300 is known for its chromatin remodeling activity, it is also part of a signal cascade and is known to be post-translationally methylated and phosphorylated. The estrogen receptor is known to be multiply phosphorylated and acetylated. It is believed that these modifications play a role in the transcriptional activation and silencing. My research focuses on the direct analysis of these transcription factors in vivo to determine their modification states and patterns using multidimensional liquid chromatography coupled to mass spectrometry. This allows determination of the modification states and patterns of these proteins throughout the cell cycle and helps to ascertain any changes that may occur upon treatment with DNA binding drugs such as cisplatin.	Chemistry (Analytical)	Neil Kelleher