Title: "Therapeutic Discovery Via Translating Bacterial Metabolic Exchange"

ABSTRACT:

Adaptive metabolic exchange is found in all kingdoms of life, yet there are only a few tools available to monitor such metabolic exchange. In our laboratory, imaging mass spectrometry (IMS) approaches are adapted to visualize both inter and intra-species exchange of secondary metabolites between small populations of bacterial cells in a spatial fashion.1,2 The interest in the development of IMS approaches to capture microbial metabolic exchange is based on the hypothesis that microbial responses have co-evolved to interact through a network of metabolic output signals and that by understanding the nature of this system wide metabolic chemical warfare we may discover the next generation therapeutic lead compounds or therapeutic paradigms. In this presentation our ongoing developments of IMS approaches to capture natural products involved in intra and inter-species communication in a spatio-temporal fashion are highlighted. These tools not only enable the discovery of new cannibalistic natural products from intensely studied organisms such as B. subtilis3 but also provide an antibiotic discovery platform against pathogens such as S. aureus. The identification and structural elucidation of novel natural products with biological activities as described in this lecture highlights the strength of imaging mass spectrometry in the investigations of natural product mediated metabolic exchange of microbial colonies.


SPEAKER BIOGRAPHY:

Dr. Pieter C. Dorrestein, associate professor, received his B.S. at Northern Arizona University (MacDonald, 1998), PhD from Cornell University (Begley, 2004). As a NIH NRSA post-doc fellow Dorrestein used high-resolution mass spectrometry methods to interrogate the biosynthesis of therapeutic agents under the supervision and co-sponsorship of Dr. Kelleher (Univ. of Illinois) and Dr. Walsh (Harvard Medical). In Sept. of 2006, Dorrestein joined UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences and the departments of Pharmacology, Chemistry and Biochemistry as an assistant prof. He was promoted to associate prof. in July 2010. Dorrestein is a member of the Center for Marine biotechnology and biomedicine, the Moores cancer center and the UCSD center for computational mass spectrometry. His research aims to develop new mass spectrometry approaches to detect and characterize natural products, adaptive metabolism for therapeutic lead discovery and to understand biological chemical communication. Dorrestein has received several honors, including the Beckman young investigator award, the V-Foundation scholar award, the PhRMA foundation award, A Lilly young investigator award in analytical chemistry and enjoys funding from the Hearst Foundation and National Institute of Health.

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