(Speaker Term: 7/1/12 - 6/30/14)
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, Room S809A Mail Stop BCM255
Houston, TX 77030-3411
Speaker’s URL: http://www.bcm.edu/genetics/?pmid=11034
LECTURE TOPICS AND DESCRIPTIONS
Evolving Responsively: Stress-induced Mutation
Old assumptions that mutations form constantly and randomly are being revised by the discoveries of novel molecular mechanisms by which bacteria and yeast induce pathways of mutagenesis, in response to stress, controlled by stress responses. These pathways increase genetic diversity specifically when cells are maladapted to their environments; that is, when they are stressed, changing fundamental ideas about evolution. Stress-response-controlled mutagenesis is important to pathogen adaptation to hosts, antibiotic-induced resistance mutations, and, possibly, evolution generally. This seminar provides a lucid explanation of these molecular mechanisms, why they are important in microbiology and infectious disease, and how they alter our view of evolution.
What Bacteria Are Teaching Us about Cancer
DNA repair proteins are well conserved throughout phylogeny, and the homologues of bacterial DNA repair proteins are known or implicated cancer genes. These genomic caretaker proteins prevent genomic instability that promotes cancer progression. Using E. coli as a premier model organism, Dr. Rosenberg’s lab is unraveling mechanisms by which important conserved caretaker proteins prevent genomic instability, and discovering new paradigms of their action that affect cancer therapy and biology.
Mutation “showers” were discovered recently in mammals as roughly 30 kb zones of multiple spontaneous mutations. Using whole-genome sequencing of bacterial cells that have undergone stress-induced mutagenesis, Dr. Rosenberg’s group has discovered the surprising phenomenon of multiple mutation showers in large genomic regions, or mutations storms. These may have dramatic, punctuating effects on the ability of genomes to evolve. This talk shows the existence of mutation storms and suggests how they may originate.
The Rebirth of Thymineless Death
The nearly 50-year-old phenomenon in which bacterial, yeast and human cells rapidly die without thymine, showing genomic instability as they do, is an important mechanism of action of cancer chemotherapies and some antibiotics but was an enigma for decades. Its mechanism remained mysterious until recently, when Dr. Rosenberg’s lab and others discovered three central pathways of thymineless death in E. coli, each with a different mechanism. The results imply sensible molecular mechanisms that can now be understood to underlie this major pathway of antibacterial and cancer chemotherapy.
BIOGRAPHICAL SKETCH – Susan M. Rosenberg
Susan Rosenberg is a molecular biologist and bacterial geneticist who studied genetic recombination in her Ph.D. with Franklin Stahl at the University of Oregon and postdoctoral work with Miroslav Radman in Paris. From 1991-1997 on the Faculty of Medicine at the University of Alberta, Edmonton, and from 1997 to present at Baylor College of Medicine in Houston, her laboratory has investigated molecular mechanisms of DNA repair and genomic instability. Her laboratory demonstrated new mutation mechanisms and discovered that stress responses activate mutation mechanisms that allow increased genetic diversity specifically when cells are maladapted to their environments; that is, when stressed. This is a shift from initial models of evolution that assumed constant mutation rates, blind to selective environments. In addition to numerous teaching awards, Dr. Rosenberg has received the 1995 Eli Lily National Cancer Institute of Canada William Rawls Prize for outstanding contribution to cancer research, the 1996 Young Scientist Award of the Genetics Society of Canada, the Michael E DeBakey Award for Excellence in Research in 2001, the NIH Director’s Pioneer Award in 2009, and the 2010 Biosphere and Humanity Medal for contributions to mutagenesis. She was elected a fellow of the American Association for the Advancement of Science in 2010.
ASM MEMBERSHIP AFFILIATION – Susan M. Rosenberg
Primary Division: H (Genetics & Molecular Biology)