The School of Molecular and Cellular Biology at the University of Illinois at Urbana-Champaign

Research in the Wilson laboratory involves studying the molecular interactions and biochemical mechanisms by which protein toxins produced by pathogenic bacteria cause their toxic effects on animal cells. When the bacterial toxins are released into the media of the host, they can interact with or even enter host cells and interfere with normal signal transduction and physiological function, thereby disrupting the delicate balance of cellular metabolism, often lethally. One project involves studying the structure, function and pathogenic mechanisms of the potent dermonecrotic toxins produced by Pasteurella multocida, Bordetella sp., E. coli, and Yersinia. Like many other toxins, these toxins are currently being used as potent tools for studying signal transduction pathways and physiological processes within cells. The laboratory is interested in understanding the underlying mechanism of how these toxins carry out their effects on these processes. For example, the laboratory has discovered that the pleiotropic effects on different tissue cells caused by the toxin from P. multocida is due to the diverse roles that the toxin’s targets have in different cell types, which in turn influence the cellular and organismic outcomes of toxin action.

Of particular interest to the laboratory is development of post-exposure anti-toxin therapeutics. This requires a global understanding of the downstream metabolic and signaling pathways that are affected by toxins, so as to identify potential sites for intervention. We have initiated proteomic and metabolomic research projects to identify biomarkers of cellular toxicity (i.e. toxicogenomics), which will be part of our new IGB Theme on Mining Microbial Genomics for Novel Antibiotics. As part of an inter-institutional collaborative effort (the NIH-sponsored Great Lakes Regional Center for Excellence in Biodefense and Emerging Infectious Diseases) to combat botulism, we are developing novel post-exposure anti-toxin therapeutics against botulinum neurotoxins as well as highly sensitive, high-throughput detection assays for distinguishing among botulinum neurotoxins. There is currently no effective antidote for preventing or reversing botulism or paralysis once exposure has occurred and symptoms of disease have initiated. A major goal of this translational biomedical research is to design novel anti-toxins for neuronal cell-specific delivery of post-exposure therapeutics.

Finally, as part of our new IGB Theme on Host-Microbe Systems, we have just begun research to exploit comparative and functional genomic technologies to study the dynamic interactions between the host and its commensal as well as pathogenic microbes, i.e. microbial ecology in the host environment. This research will initially focus on the complex ecosystem of the vaginal microbiota and its impact on health and disease in human and nonhuman primates. A central goal will be to elucidate pathogenic mechanisms of vaginal infections such as bacterial vaginosis and the role of normal and abnormal microbiota in disease susceptibility and progression. Studying both human and nonhuman primate vaginal ecosystems has the potential to address human biomedical questions by establishing an evolutionary and comparative biology context that considers environments, microbes, and host immune systems.