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Microbes in Health and Disease Training Grant

Humans have evolved to live with microbes: to defend against those that harm us, and maintain those that are beneficial. Microbes too have evolved diverse metabolic activities that allow them to thrive in a wide variety of habitats and in association with all living creatures. The result of this coordinated evolution is a spectacular diversity of interactions between microbes and the world, and a diversity of ways in which microbes affect our lives. Our expanded program is designed to train students and postdoctoral fellows in the use of cutting-edge tools to investigate the microbe-animal interface and microbe contributions to human health and disease.

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Trainee Paper

Jon Palmer

Past Postdoc in Nancy Keller's Lab

Currently a Postdoc in Nancy Keller's Lab at UW-Madison

"RsmA Regulates Aspergillus fumigatus Gliotoxin Cluster Metabolites Including Cyclo(L-Phe-L-Ser), a Potential New Diagnostic Marker for Invasive Aspergillosis"

Abstract: Dimeric basic leucine zipper (bZIP) proteins are conserved transcriptional enhancers found in all eukaryotes. A recently reported and novel function for bZIPs is association of these proteins with secondary metabolite production in filamentous fungi. In particular a Yap-like bZIP termed RsmA (restorer of secondary metabolism A) was identified in Aspergillus nidulans that positively regulates the carcinogen sterigmatocystin. To assess for conserved function for RsmA, we examined a role of this protein in secondary metabolism in the pathogen A. fumigatus. RsmA was found to positively regulate gliotoxin where overexpression (OE) of rsmA led to 2-100 fold increases of twelve gli cluster metabolites in culture medium including the newly identified gli metabolite cyclo(L-Phe-L-Ser). Lungs from both wild type and OErsmA infected mice contained gliotoxin (2.3 fold higher in OErsmA treatment) as well as the gliotoxin precursor cyclo(L-Phe-L-Ser) (3.2 fold higher in OErsmA treatment). The data here presents a conserved role for RsmA in secondary metabolite cluster activation and suggests cyclo(L-Phe-L-Ser) may serve as an alternative marker for diagnosis of invasive aspergillosis.

Details : Sekonyela R, Palmer JM, Bok JW, Jain S, Berthier E, Forseth R, Schroeder F, and NP Keller. PLoS One. 2013 May 6;8(5):e62591.

University of Wisconsin-Madison
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Madison, WI 53706-1521

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Last Updated: May 30, 2013