Harvard Medical School professor to give lecture on bacterial toxins at Virginia Bioinformatics Institute
May 13, 2009
R. John Collier, Maude and Lillian Presley Professor of Microbiology and Molecular Genetics at Harvard Medical School, will visit the Virginia Bioinformatics Institute at Virginia Tech on May 21 and 22 to discuss his research on the function of bacterial toxins, including how this work can be used to develop countermeasures against anthrax.
Collier, a member of the National Academy of Sciences, is a pioneer in elucidating the structures and modes of action of bacterial protein toxins. Collier received the National Academy of Sciences Selman Waksman Award in 1999 and the Abbott-ASM Lifetime Achievement Award of the American Society for Microbiology in 2006. His laboratory was the first to demonstrate how a protein toxin, in this case diphtheria, can penetrate mammalian cells and directly modify its protein target.
Collier will present the talk, “How Bacterial Toxins Cross Membranes: The Anthrax Toxin Example,” on Thursday, May 21, from 3:30 to 5:30 p.m. at the Virginia Bioinformatics Institute conference center, which is located on Washington Street on the Virginia Tech campus.
Many bacterial toxins are extraordinary enzymes that have the capacity to penetrate from the external medium to the cytosolic compartment of mammalian cells. How this occurs is not yet understood in great detail for any toxin, but considerable progress has been made recently in the case of anthrax toxin. Collier will reveal what is known at the molecular level about how anthrax toxin invades cells and how it ultimately leads to disease. He will also discuss the potential uses of this knowledge in developing new countermeasures against anthrax.
In addition to the presentation, informal meetings will be scheduled on Friday, May 22, to give Virginia Tech students, faculty, and staff members an opportunity to learn about Collier’s research and activities. Collier will meet with faculty and staff from the Virginia Bioinformatics Institute and other departments at Virginia Tech from 10 a.m. until noon, and will attend a lunch meeting with interested graduate students and postdoctoral researchers from noon until 1 p.m. Those interested in meeting with Collier should send an email to Emily Alberts.
Collier is a Maude and Lillian Presley Professor of Microbiology and Molecular Genetics at Harvard Medical School. He has been a pioneer in elucidating the structures and modes of action of bacterial protein toxins. Early in his career he discovered that diphtheria toxin inactivated mammalian elongation factor-2 by an NAD-dependent mechanism, later identified as ADP-ribosylation.
This represented the first demonstration that a protein toxin can penetrate the cytosol of mammalian cells and directly modify a target substrate. Later efforts by many laboratories led to the realization that the ability to penetrate to the cytosol and modify intracellular targets is shared by a broad array of bacterial toxins, including anthrax toxin, cholera toxin, pertussis toxin, tetanus toxin, botulinum toxin, and many others.
As a faculty member at the Department of Microbiology, University of California, Los Angeles, Collier defined basic structure-function relationships in diphtheria toxin. He showed that its action depended on proteolytic activation, leading to the classical AB toxin model. Using novel photolabeling technology, he identified glutamic acid 148 of diphtheria toxin as a critical catalytic residue that was later found to be conserved throughout the ADP-ribosyltransferases. He crystallized diphtheria toxin and toxin A from Pseudomonas aeruginosa and initiated structure determination of these toxins.
After joining Harvard, Collier turned his attention to the question of how protein toxins cross membranes. His studies on diphtheria toxin and anthrax toxin in recent years have revealed much about the molecular mechanisms by which the enzymic moieties of these toxins are delivered into cells. His studies on the protective antigen component of anthrax toxin have shown that this protein forms pores in the endosomal membrane, which mediate translocation of the enzymatic lethal and edema factors across the membrane. His collaboration with John Young led to identification of the first known receptor for anthrax toxin.
Collier has received many honors, including the Eli Lilly Award in Microbiology and Immunology in 1972, the Paul Ehrlich Prize in 1990, the National Academy of Sciences Selman Waksman Award in 1999, The Bristol-Myers Squibb Award in Infectious Disease Research in 2003, and the Abbott-ASM Lifetime Achievement Award of the American Society for Microbiology in 2006. He was elected to the National Academy of Sciences in 1991.