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.

2008-2010 Trainees	Home Department	CBI Mentor
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
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.		Ryan C. Bailey

2007-2009 Trainees	Home Department	CBI Mentor
Matthew DeSeino Research Description: My research involves the biosynthetic pathway of FR-900098, a phosphonic acid with potential as a novel chemotherapeutic against malaria. Through feeding experiments, mass spectrometry and 31P-NMR analysis, the required enzymes for heterologous production of the compound in E. coli can be identified. Once the pathway has been elucidated, protein engineering of these enzymes can create various FR-900098 derivatives and metabolic engineering can be used to overproduce the desired FR-900098.	Chemical & Biomolecular Engineering	Huimin Zhao
Jessica Frisz Research Description: My research focuses on the separation of nucleic acids and proteins on the same platform. Because DNA is easy to synthesize and more robust than protein, it is used as the foundation of the method. Short DNA strands are conjugated to antibodies, which bind to a target ( i.e, a protein or cell) and then are flowed over a surface spotted with the complementary DNA strand. When the DNA strands hybridize, the antibody and its target are trapped at a specific location on the surface. This method can to scaled to accommodate many different targets and several parameters.	Chemistry (Chemical Biology)	Ryan C. Bailey
David Knapp Research Description: As a graduate student in the Burke Group, my current project involves the synthesis of a mycosamine sugar building block, as part of the Amphotericin B total synthesis effort. Mycosamine sugars are ubiquitous among polyene macrolide antibiotics, and their efficient attachment to the parent macrocyle is an as-of-yet unsolved problem that has hampered the study of this important class of drugs. The current synthetic plan will also allow access to amphotericin B derivatives, whose potency against yeast fungal cells will offer insight into amphotericin’s mechanism of action. A better understanding of how amphotericin B forms membrane-spanning ion channels will ultimately provide the groundwork for the development of a synthetic ion channel mimic, a potential treatment for currently incurable diseases like cystic fibrosis.	Chemistry	Martin D. Burke
Julia Martin Research Description: The sulfhydryl of cysteine residues may play an important role in the defense against hydrogen peroxide (H2O2) stress. The formation of disulfide bonds amongst cysteine residues promotes protein stability and function and assist in redox regulation. Disulfide bonds are rarely observed in cytoplasmic proteins and a minute level of H2O2 is found in wild type Escherichia coli cells, suggesting that even at low levels H2O2 is harmful. Only two known proteins directly interact with hydrogen peroxide through sulfhydryls: OxyR and AhpC. During H2O2 stress, OxyR is activated by the formation of an intramolecular disulfide bond through its interaction with H2O2. Oxidized OxyR in return induces the transcription of antioxidant genes (trxC, grxA, gor) involved in the reduction of sulfhydryls. It is unclear why OxyR upregulates these genes and what physiological role these proteins play during H2O2 stress. As part of the thioredoxin and glutaredoxin systems, these proteins may play a key role in fixing inappropriate disulfide bond formations or recycling enzymes such as ribonucleotide reductase and phosphoadenosine-phosphosulfate (PAPS) reductase through disulfide bond exchanges. They may also aid in turning off the OxyR response.	Microbiology	James A. Imlay
Matthew Olsen Research Description: My research involves the synthesis of models for the active site of Fe-only hydrogenase. Hydrogenases are remarkable because they reversibly interconvert dihydrogen to protons and electrons using iron. They operate at near thermodynamic efficiency, use an inexpensive metal, and are only reversibly inactivated by CO, making their biomimetic modeling applicable to the design of fuel cells. Furthermore, a hydrogenase-based metabolism supports the pathogen H. pylori, which solely infects the mucosal lining of the human stomach where it gives rise to ulcers and gastric cancer. Therefore, hydrogenase models are also biomedically relevant. A complete mechanistic understanding of hydrogenases can be developed by the study of structural models	Chemistry	Thomas B. Rauchfuss
Quinn Peterson Research Description: Apoptosis is the mechanism by which cells commit suicide in response to intrinsic and extrinsic signals during cell stress or development. The pathways activated in response to these signals involve the activation of a class of cysteine proteases known as caspases. Ultimately caspase-3, an executioner caspase, is activated and in turn proteolyses its cellular substrates resulting apoptosis. Cancer is characterized by the ability of cells to evade apoptosis through mutation and misregulation of key apoptotic proteins including caspases. Counter intuitively cellular levels of procaspase-3 are often elevated in cancer cells. Despite being primed for apoptosis, activation of procaspase-3 does not occur in cancer cells due to upstream mutations in proapoptotic proteins, and aberrant expression levels of certain anti-apoptotic proteins; these alterations prevent apoptotic signals from reaching procaspase-3. A small molecule which directly activates procaspase-3 to caspase-3 could provide the potential for new approaches for cancer therapy. In a screen for small molecule activators of procaspase-3, a novel compound, PAC-1, was identified. This compound was shown to directly activate procaspase-3 to caspase-3 in vitro, kill cancer cells in culture and inhibit tumor growth in mouse xenograft models. Further mechanistic characterization of this compound and the development of more potent derivatives are in progress.	Biochemistry	Paul J. Hergenrother

2006-2008 Trainees	Home Department	CBI Mentor
Quin Christensen Research Description: Lipoate is a necessary cofactor for several enzymes involved in oxidative and single carbon metabolism in aerobes. Mice deficient in lipoate biosynthesis perish during embryogenesis.  Lipoic acid (Thioctic Acid) biosynthesis has recently been elucidated in Escherichia coli .  The lipoyl domain is modified by octanoate, which is then converted to lipoate by a radical SAM mechanism.  The lipoyl domain can also be modified with free lipoic acid via a scavenge pathway.  The goal of my project is to begin to examine the diversity of lipoyl domain modification in other organisms.  This will be done using genetic, bioinformatic, and biochemical tools available.	Microbiology	John Cronan
Victor Gonzalez Research Description: My project focuses on the synthesis of coactivator binding inhibitors that may be used to inhibit the transcriptional activity of nuclear receptors (e.g., estrogen receptor).	Chemistry (Organic)	John Katzenellenbogen
Ian Gut Research Description: Determining the effects and mechanisms of nisin on Bacillus anthracis and the effects of nisin on Bacillus anthracis and macrophage interactions.	Microbiology	Steven Blanke Wilfred van der Donk
Raymond Morales Research Description: Topoisomerases are ubiquitous and essential enzymes involved in a range of cellular activities from chromosome segregation to gene transcription. In recent years, these molecular machines have become a target for cancer treatments. Our lab contains a library of the clones from the mesophile Methanosarcina acetivorans that include the topoisomerases from this organism. As the largest sequenced genome among Archaea, M. acetivorans contains a diverse array of proteins. In some instances, Archaeal proteins correlate well with Eukarya or Bacteria. In others, novel activity has been discovered specific to the organism. We plan to functionally characterize these Archaeal topoisomerases to determine the residues that are required for catalytic activity and to make evolutionary inferences about the relationships amongst the domains of life.	Microbiology/Medical Scholar	Isaac K.O. Cann
Alex Parent Research Description: The androgen receptor (AR) is a member of the nuclear receptor superfamily and plays a significant role in the development of male sexual characteristics. AR plays an integral part in the formation and growth of prostate cancer, traditional prostate cancer therapy centering on inhibition of this nuclear receptor. Although initial treatment with androgen ablation therapy produces positive results in prostate cancer patients, most eventually lapse into a state of hormone refractory prostate cancer, for which there is no substantive treatment. Consequently, there is a need for new molecular approaches to AR inhibition. My project will focus on one of these approaches, namely, disruption of the AR/coactivator complex through the design and synthesis of small molecule-coactivator binding inhibitors.	Chemistry (Organic) Medical Scholars Program	John Katzenellenbogen
Kara Smith Research Description: Poly (lactide-co-glycolide) microspheres and microcapsules show great promise as biodegradable controlled-release drug delivery systems for therapeutic proteins. However, PLGA degradation byproducts can lower the pH of the microenvironment, thus affecting protein stability. My research focuses on the potential stability benefits of using aqueous-core PLGA microcapsules for protein delivery.	Chemical & Biomolecular Engineering	Daniel Pack