Jason Sello
Assistant Professor:
Chemistry
Phone: 401 863 1194
jason_sello@brown.edu
My research is inspired by naturally occurring antibiotics and the organisms from which they come. Streptomyces bacteria and their antibiotics are the primary subjects of my research. These soil-dwelling bacteria produce half of the 10,000 known antibiotics and about two-thirds of the medicinal natural products (e.g. FK506, tetracycline, daptomycin, and doxorubicin.) My interests are the molecular mechanisms in Streptomyces bacteria that underly the production of and resistance to antibiotics.
Biography
Prof. Sello earned a B.S. in biology from Morehouse College in 1997 and a Ph.D. in biophysics in 2002 from Harvard University. His doctoral research in diversity-oriented organic synthesis was carried out in the laboratory of Prof. Stuart L. Schreiber in the Department of Chemistry and Chemical Biology. He performed post-doctoral research in enzymology with Prof. Christopher T. Walsh at Harvard Medical School and in Streptomyces genetics with Prof. Mark J. Buttner at the John Innes Centre in Norwich, England. He is currently using experimental methods from chemistry, molecular biology and biochemistry to study antibiotic production by Streptomyces bacteria.
Interests
I study antibiotic biosynthesis as a physiological phenomenon. Recent advances in experimental chemistry and biology make it is possible to analyze antibiotic biosynthesis on a scale and at a resolution previously unimaginable. My training in synthetic chemistry, protein biochemistry, and molecular genetics enables me to capitalize on the emerging opportunities in this interdiscplinary research area. With this broad expertise, I am prepared to carry out penetrating, "system-level" analyses of antibiotic production in vivo. The subject of my studies will be Streptomyces bacteria. These soil bacteria and their close relatives among the actinomycetes are best known as producers of nearly two-thirds of the 10,000 known antibiotics, many of which have tremendous value in clinical and veterinary medicine (e.g., FK506, tetracycline, bleomycin, doxorubicin, vancomycin, erythromycin, and avermectin). Since the 1950s, pharmaceutical companies have fermented these organisms on very large scales to produce many of our medicines. Accordingly, much is known about their genetics and physiology. However, there is much to be learned about the molecular mechanisms that enable and regulate antibiotic production in streptomycetes and actinomycetes in general. To advance knowledge of these mechanisms I will study the best-characterized actinomycete, Streptomyces coelicolor A3(2), which produces four chemically distinct antibiotics via discrete biosynthetic pathways. Much about this organism is known as it has been studied intensively for over half of a century. Its genome has been sequenced and powerful tools for systematic gene manipulation, transcription profiling, and proteome analyses of S. coelicolor have been developed. These tools have yielded important new insights into Streptomyces biology. Although the changes in gene expression during antibiotic production have been measured, the corresponding changes in the concentrations of metabolites have not been characterized. To illuminate these changes, I will develop methods that enable measurement of the flux of low-molecular weight metabolites into pathways for antibiotic production. In addition, I will synthesize compounds that are capable of perturbing metabolic flux. These tools will be used synergistically with established biochemical methods for transcriptomics and proteomics to generate a molecular resolution description of the changes in Streptomyces physiology during antibiotic production. These methods will also be useful in comparative analyses of wild-type Streptomyces strains and those optimized by the pharmaceutical industry for the production of large quantities of antibiotics. These analyses are likely to reveal the cryptic physiological features associated with the over-production of antibiotics. Recognition of these features may suggest how streptomycetes can be rationally engineered for the production of large quantities of antibiotics.
Awards
- 2003 Burroughs Wellcome Fund Career Award at the Scientific Interface
- 2000 Certificate of Distinction in Teaching for "Biological Sciences 1: Introduction to Molecular Biology", Harvard University
- 1998 Glaxo-Wellcome-UNCF Scientific Achievement Award
- 1997 Pre-doctoral Fellowship, National Science Foundation
- 1997 magna cum laude graduate of Morehouse College
- 1997 Phi Beta Kappa, Morehouse College
- 1997 J. K. Haynes Award for Outstanding Senior Biology Major
- 1997 Scholarship, Achievement Awards for College Scientists- Atlanta Chapter
- 1995- 1997 Minority Access to Research Careers (MARC) Scholar
- 1995-1997 Howard Hughes Medical Institute Undergraduate Scholar
- 1993-1997 Morehouse College Dean's List
- 1993-1997 Morehouse College Academic Scholarship for Tuition
Affiliations
American Chemical Society
American Society for Microbiology
American Society for Biochemistry and Molecular Biology
Society for Industrial Microbiology
Teaching
Small molecules produced by organisms for chemical defense have long been exploited in medicine, biotechnology, and biological research. "CH0156: The Chemistry and Biology of Naturally Occurring Antibiotics" examines the origins, uses, modes of action, and preparations of some of the most important and useful of these 'antibiotic' molecules. Given the inter-disciplinary nature of this topic, this course is open to students with backgrounds in the biological and/or physical sciences. Familiarity with concepts of organic chemistry and biochemistry will be assumed.
Funded Research
- 2003- 2008 Career Award at the Scientific Interface Burroughs Wellcome Fund
($500,000 over five years) - 2002- 2003 UNCF-Merck Post-doctoral Fellowship
- 2001- 2002 Graduate Prize Fellowship Harvard University
- June- September 2001 International Research Travel Grant Burroughs Wellcome Fund
($5,000 support for three months work at the John Innes Centre, United Kingdom) - 2000-2001 Pharmacia Graduate Fellowship Division of Organic Chemistry
American Chemical Society - 1997- 2000 Pre-doctoral Fellowship, National Science Foundation
