Christopher T. Walsh, Ph.D.
“Bacterial-Host Iron Wars”
Tuesday, Sept. 26, 2006, 12:30 p.m. – 1 p.m.
Searle Center Lecture Hall
(With broadcast to Fitzpatrick CIEMAS lobby)
Bacteria need iron to grow. In iron-poor microenvironments they turn on biosynthetic genes to make, secrete, and retrieve siderophores that scavenge ferric iron from the surroundings. Enterobactin, a prototypic iron scavenging metabolite made on a nonribosomal peptide synthetase assembly line, has an estimated KD of 10-49 M for ferric iron.
Mammalian hosts fight back by sequestering iron in serum via serum albumin and a neutrophil-derived lipocalin termed siderocalin. Some virulent bacteria counterattack by an unusual enzymatic C-glycosylation of the enterobactin scaffold, generating salmochelins (first detected in virulent salmonella) where the bulky glucosyl moiety now abrogates sequestration of this tailored siderophore by siderocalin, allowing retrieval of the iron-loaded form by the bacteria.
Christopher T. Walsh is the Hamilton Kuhn Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School (HMS). He has had extensive experience in academic administration, including Chairmanship of the MIT Chemistry Dept (1982-1987) and the HMS Biological Chemistry & Molecular Pharmacology Dept (1987-1995) as well as serving as President and CEO of the Dana Farber Cancer Institute (1992-1995).
His research has focused on enzymes and enzyme inhibitors, with recent specialization on antibiotics and biosynthesis of other biologically active natural products. He and his group have authored over 645 research papers, books on Enzymatic Reaction Mechanisms(1979); Antibiotics: Origins, Actions, Resistance (2003); Posttranslational Modification of Proteins: Expanding Nature’s Inventory (2005). He is a member of the National Academy of Sciences, the Institute of Medicine, the American Academy of Arts and Sciences, and the American Philosophical Society.
He has been a consultant to government and academic institutions, including NIGMS, a Trustee of the Whitehead Institute and the Helen Hay Whitney Foundation and a member of the scientific review board of HHMI. He also has been a consultant to large pharmaceuticals (Merck, Roche, and Abbot), and been involved in scientific advisory capacity for such companies as Genzyme, Immunogen, Kosan Biosciences, and Millennium. He has been or is currently on the Board of Directors of Critical Therapeutics, Kosan, Immunogen, Leukosite. Microbia, Transform, and Vicuron. He has been a scientific advisor to venture capital groups such as Health Care Ventures.
At Harvard he teaches biochemistry, chemical biology, and pharmacology to medical students and graduate students. He is chair of the faculty standing committee of the Harvard Integrated Life Sciences graduate programs.