Current 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.

2009-2011 Trainees	Home Department	CBI Mentor
Mike Brothers Research Description: My research uses the latest techniques in structural biology, including molecular modeling, simulations, and Solid-State NMR (SSNMR) to determine the structure, dynamics, and binding affinities of toxins of DHS interest. Currently, my research is focused on Pasteurella multocida toxin (PMT) and Staphylococcus enterotoxin C3. PMT is transmitted by the zoonotic bacterium Pasteurella multocida and is one of the most potent known mitogens. It is our goal to understand its binding affinity and its mechanism of entry into the target cell. This includes determination of the structure of the binding domain when PMT is in the endosome using (SSNMR). Staphylococus enterotoxin C3 is a Department of Homeland Security select agent released by the bacterium Staphylococcus aureus and is a causative agent in food poisoning. Our goal is to use Solid-State NMR to assign the chemical shifts for the toxin and to then determine the dynamics of the flexible disulfide loop, which is essential for virulence, in complex with MHC-II and CD4.	Chemistry	Chad M. Rienstra Brenda A. Wilson
Ryan Cobb Research Description: My current research in the Zhao Lab is focused on two main projects. The first involves FR-900098, a phosphonate compound with great potential as an anti-malarial drug. I am currently investigating the catalytic activity of FrbF, an N-acetyltransferase enzyme in the biosynthetic pathway. Through directed evolution, the substrate specificity of FrbF can be altered, allowing for the creation of novel FR-900098 derivatives with the potential for greater efficacy. The second project involves the characterization of cryptic gene clusters from Streptomyces griseus. Using a DNA Assembly method developed in our lab, a desired cryptic pathway can be amplified from genomic DNA and assembled into a large plasmid for heterologous expression and product detection.	Chemical & Biomolecular Engineering	Huimin Zhao
Vanessa Iiams Research Description: Orotidine 5'-monophosphate decarboxylase (OMPDC) increases the formation of uridine 5'-monophosphate from OMP by a factor of 1017, one of the largest rate accelerations by protein catalysis known. However, the catalytic mechanism driving the rate enhancement remains unclear. My project focuses on enzyme mutagenesis and complementary synthesis of substrate analogs to uncover contributions from active site residues to rate enhancement.	Chemistry	John A. Gerlt
Patrick Knerr Research Description: The fascinating and diverse biological activities of many cyclic peptide natural products result from intricate secondary structures created by networks of disulfide and thioether bonds. Some of these compounds, including the antimicrobial lantibiotic family and the conotoxin family of neuroactive venom peptides, can be isolated from natural sources but have been challenging to produce in the laboratory. My work focuses on the synthesis of such interesting peptides using both chemical and enzymatic means to install the sulfur-based ring structures. This in vitro approach can be applied to develop structure-activity relationships for these compounds, to probe modes-of-action and to synthesize modified analogues with potentially improved potency	Chemistry	Wilfred van der Donk
Caroline Milne Research Description: In my research project I am looking to use systems biology modeling techniques to globally analyze the metabolism of Clostridium beijerinckii and increase its ability to produce butanol -- a promising alternative fuel. C. beijerinckii advantageously produces butanol as a natural byproduct of its fermentation, and can co-ferment both pentoses and hexoses (the two primary sugars produced in hydrolysis of lignocellulose). We aim to reconstruct the metabolic network of C. beijerinckii, and computationally predict a strain that overcomes the economic challenge of low butanol concentration during fermentation. Once we have generated model-based hypotheses for a enhanced butanol producing strains, we will create and test these strains experimentally.	Chemical & Biomolecular Engineering	Nathan D. Price

2008-2010 Trainees	Home Department	CBI Mentor
Jung-un Baek Research Description: The focus of my research is to provide chemical tools to study alternative splicing. My first project is to develop a small molecule activated switch for alternative splicing. The general approach I am using to control splicing is to engineer an RNA binding protein that is involved in alternative splicing such that it will bind to RNA only in the presence of a small molecule. The small molecule will thus act as a switch to turn on RNA binding and as a result alternative splicing. The other project is to use bipartite tetracysteine display for rapid and direct detection of RNA splicing. This method can be used for high throughput screening of small molecules that activate or inhibit splicing. And by attaching a cell penetrating peptide this could potentially become a powerful tool to visualize splicing in living cells.	Chemistry	Anne M. Baranger
Lindsey Johnstone Research Description: Lantibiotics are a special class of antimicrobial peptides containing unusual amino acid residues, including dehydrobutyrine and dehydroalanine, as well as lanthionine-rings, from which these peptides take their name. The most well-known of these is nisin, a 34-residue peptide that has been used extensively in the food industry as a preservative. I will be studying details of its mode of action. Though it is by far the most studied of the lantibiotics, there is still much to be learned.	Chemistry	Chad M. Rienstra and Wilfred van der Donk
Nick Marshall Research Description: Studying the molecular interaction in electron transfer proteins that affect various properties of the proteins, such as reduction potential. De-convoluting the individual reactions for the purposes of studying biological electron transport and to allow for the rational design of bio-inspired electronics	Chemistry	Yi Lu
Amit Sachdeva Research Description: NA Catalysis and Development of Deoxyribozymes for Proteins and Small-Molecule Substrates Deoxyribozymes are single-stranded DNA molecules that have the ability to catalyze various bioorganic reactions. Deoxyribozymes do not occur naturally, hence are selected by a combinatorial technique called in vitro selection. Since the discovery of the first artificial deoxyribozyme that catalyzes the phosphodiester bond cleavage reaction in RNA molecules, a number of deoxyribozymes have been selected to catalyze different bioorganic reactions including RNA ligation, DNA ligation, DNA phosphorylation, DNA glycosylation, oxidative cleavage of DNA and Diels-Alder reaction. However, most of these reactions involve oligonucleotide substrates. A major challenge is to include small molecules, proteins and other substrates into the repertoire of DNA-catalyzed reactions. This would allow development of deoxyribozymes for different bioorganic reactions for which effective catalysts do not exist. Addressing this challenge, my specific aims are to develop a methodology that can utilize any small molecule or protein substrate for an in vitro selection procedure and to identify deoxyribozymes to catalyze nucleopeptide linkage formation and phosphorylation reactions.	Chemistry	Scott K. Silverman
Christine Toh Research Description: The goal of my project is to create multi-component gradients of biomolecules on surfaces that can be used for the stratification of heterogeneous cell populations according to their cell surface composition. These surfaces may ultimately serve as a diagnostic platform to asses the metastatic potential of cancer cells from a tumor biopsy sample and allow for single-cell drug efficacy trials on a patient's exact cancer, leading to personalized, disease-specific chemotherapies.	Chemistry	Ryan C. Bailey
Juan Velasquez Research Description: As a member of the van der Donk Group and the Mining Microbial Genomes Theme (MMG) at the Institute for Genomic Biology, I have been working on two particularly promising groups of antimicrobial compounds: lantibiotics and phosphonates. The construction of genomic DNA libraries of producer organisms has allowed me to identify the gene clusters potentially involved in the biosynthesis of the recently discovered lantibiotic epilancin 15X and some other potentially novel phosphonates. In addition, screening cell-free extracts for the presence of phosphonates, I identified the production conditions for two potentially novel compounds. Over the next few years, I will be working towards cloning, overexpression, in vitro reconstitution, and characterization of individual enzymes in their biosynthetic pathways.	Chemistry	Wilfred van der Donk