Students are in bold italics; faculty in bold.
Honors Reseach in Biochemistry (2009)
Bryan Stefek '09 presented "Production of Hydrogen Cyanide in Chromobacterium violacium Is under Quorum Sensing Control" at the Rochester chapter of the American Chemical Society. 2009. The research was carried out with Scott Ulrich in the chemistry department.
Abstract
Chromobacterium violacium is lethal to the soil nematode C. elegans when ingested. This pathogenicity is controlled by a signaling system found in many bacteria called "quorum sensing" such that the bacterium is not lethal when quorum sensing is genetically or chemically disabled. As such, this a useful model system to determine if anti-quorum sensing drugs could serve as a new type of antibiotic.
Bryan's talk described his research to find what specific genes that are under quorum sensing control mediate this pathogenicity. He found that Chromobacterium violacium makes hydrogen cyanide, a generic biocide, and he could block HCN production by chemical or genetic inhibition of quorum sensing.
Honors Reseach in Biochemistry (2008)
Lei Mi-Mi (Supervised by Marina Caillaud) “Analysis of two host races of the pea aphid using
microarray technology
Pamela Ronco (Supervised by Ed Cluett) "Effects of phospholipase A2 inhibitors on the processing of amyloid precursor protein ”
Eric VanFleet, Martin Tomov and Vicki Cameron (2008). NCUR, Salisbury, MD. April 2008. "Deletion of the Nuclear Gene YME1 Stabilizes Mutant forms of Cox2p".
Samantha Palmer (Marina Caillaud). (2006) Poster Presentation. “Variation in gene expression in caterpillars of the tobacco hornworm”. Samantha received an honorary award for her poster.
Martin Tomov and Vicki Cameron (2006). Regional Sigma Xi Meeting, Cornell University. "Stabilization of mutant forms of Cox2p by deletion of YME1 and overexpression of PETIII".
Biochemistry students Colleen O'Loughlin and Raleene Gatmaitan and chemistry department chair Scott Ulrich coauthored a paper in the Molecular Cell journal.
The paper is titled "A Quorum Sensing Antagonist That Targets Both Membrane-Bound and Cytoplasmic Receptors Controls Bacterial Pathogenicity."
In addition to O'Loughlin, Gatmaitan, and Ulirch, the paper's other coauthors were Lee Swem, Danielle Swem, and Bonnie Bassler of Princeton University. The article has just been accepted and will appear in print and online shortly.
Abstract
Quorum sensing is a process of bacterial cell-cell communication that involves production and detection of secreted signal molecules called autoinducers. Gram-negative bacteria use acyl-homoserine lactones (AHLs) as autoinducers which are detected by one of two receptor types. First, cytoplasmic LuxR-type receptors bind accumulated intracellular AHLs and the AHL-LuxR complexes bind DNA and alter gene expression. Second, membrane-bound LuxN-type histidine kinase receptors bind accumulated extracellular AHLs. The AHL-LuxN complexes relay information internally by phosphorylation cascades that impinge on downstream DNA binding proteins that direct changes in gene expression. Here we describe that a small molecule scaffold, previously identified as an antagonist of LuxN-type receptors, is also a potent antagonist of the LuxR family, despite the differences in receptor structure, localization, AHL specificity and mechanism of signaling. We also describe the key biochemical differences between the antagonized and agonized form of the LuxR family receptor. A focused library of derivatives of the original antagonist was synthesized and optimized for potency. Remarkably, the most potent antagonist protects the model eukaryote Caenorhabditis elegans from the bacterial pathogen Chromobacterium violaceum, validating the idea that quorum sensing inhibitors have potential clinical use as novel antimicrobials.
Colleen O'Loughlin, Raleene Gatmaitan and Scott Ulrich, Lee Swem, Danielle Swem, and Bonnie Bassler. (In print 2009). "A Quorum Sensing Antagonist That Targets Both Membrane-Bound and Cytoplasmic Receptors Controls Bacterial Pathogenicity." Molecular Cell.
ABSTRACT: Quorum sensing is a process of bacterial cell-cell communication that involves production and detection of secreted signal molecules called autoinducers. Gram-negative bacteria use acyl-homoserine lactones (AHLs) as autoinducers which are detected by one of two receptor types. First, cytoplasmic LuxR-type receptors bind accumulated intracellular AHLs and the AHL-LuxR complexes bind DNA and alter gene expression. Second, membrane-bound LuxN-type histidine kinase receptors bind accumulated extracellular AHLs. The AHL-LuxN complexes relay information internally by phosphorylation cascades that impinge on downstream DNA binding proteins that direct changes in gene expression. Here we describe that a small molecule scaffold, previously identified as an antagonist of LuxN-type receptors, is also a potent antagonist of the LuxR family, despite the differences in receptor structure, localization, AHL specificity and mechanism of signaling. We also describe the key biochemical differences between the antagonized and agonized form of the LuxR family receptor. A focused library of derivatives of the original antagonist was synthesized and optimized for potency. Remarkably, the most potent antagonist protects the model eukaryote Caenorhabditis elegans from the bacterial pathogen Chromobacterium violaceum, validating the idea that quorum sensing inhibitors have potential clinical use as novel antimicrobials.
Krenuhrubec K, Marshall BL, Hedglin M, Verdin E., Ulrich, S. (2007) "Design and evaluation of "Linkerless" hydrozamic acids as selective HDAC8 inhibitors."Bioorg Med Chem Lett. 17: 2874-2878.
Pawlicki, J. M., Pease, L. B., Pierce, C. M., Startz, T. P., Zhang, Y. and Smith, A. M. (2004). “The effect of molluscan glue proteins on gel mechanics”. Journal of Expermental Biology, 207: 1127-1135.
Werneke, S. W., Swann, C., Farquharson, L. A., Hamilton, K. S. and Smith, A. M. (2007) “The role of metals in molluscan adhesive gels.” Journal of Experimental Biology, 210: 2137-2145.
Zhang, X, Haaf, M., Todorich B, Grosstephan E, Schieremberg, H, Surguladze N, Connor JR. (2005) "Cytokine toxicity to oligodendrocyte precursors is mediated by iron." Glia 52: 199-208.
