Stephen Winans

I earned my PhD at the Massachusetts Institute of Technology in 1984 studying conjugative drug resistance plasmids, and did post-doctoral work at the University of Washington studying Agrobacterium tumefaciens, which causes tumors on host plants.  I joined the department in 1988, continuing both areas of research.  My main teaching responsibilities are one course on the molecular mechanisms of bacterial and viral pathogenesis of humans, and another course about the origin of life.

Research Focus

I have been a member of the Department of Microbiology since 1988. I obtained his PhD degree in Biology at M.I.T., working with Graham Walker, and did postdoctoral studies at the University of Washington with Eugene Nester. As a postdoctoral fellow, I helped describe how the plant pathogenic bacterium Agrobacterium tumefaciens detects chemical cues that are released from plant wound sites, and uses this information to transcribe genes that direct the disease process. The detection of these signals requires one of the first-described two-component regulatory systems, composed of a sensory histidine kinase and a phosphorylated response regulator. I have continued with these studies at Cornell University.

Since joining the Cornell faculty, our lab has used Agrobacterium to continue studies of chemical ecology. We have elucidated how Agrobacterium detects a variety of plant-released chemical cues. Beginning in the early 1990’s, our lab broadened its focus to study how this bacterium can detect chemical signals released by sibling bacteria. Thanks in part to his work, we now know that many bacteria use diffusible molecules as pheromones to estimate their population density and to coordinate their physiologies. This phenomenon is sometimes referred to as quorum sensing, a term that we coined in a review article. Quorum sensing in Agrobacterium requires TraI and TraR proteins, where TraI synthesizes the pheromone in this system, while TraR is a pheromone receptor and pheromone-dependent transcription factor. Our group was the first to purify any protein in the TraI family and reconstitute its pheromone synthesis activities in a purified system.

We then turned our attention to the pheromone receptor protein TraR. We did the first purification of any member of the TraR family and reconstituted all of its properties in a purified system. One interesting discovery was that TraR cannot fold into a soluble, functional form in the absence of its pheromone, indicating that the pheromone acts as a scaffold for protein folding. The same was later shown to be general property of most of these proteins. We also collaborated in obtaining the high-resolution crystal structure of TraR-pheromone-DNA complexes. A decade later, no other member of this family has been crystallized in such a ternary complex.

We also study the quorum-sensing systems of two other bacteria, Burkholderia cenocepacia, and of Yersinia enterocolitica, both human pathogens. The CepR and CepI proteins of B. cenocepacia follow the same general patterns as the TraR and TraI proteins, in that CepI makes a pheromone that CepR needs for activity. However, this organism also expresses a protein called CepR2, which resembles CepR, and which detects the pheromone made by CepI. However, CepR2 is active only in the absence of this pheromone.

The YenI and YenR proteins of Y. enterocolitica also have some surprising properties. Like CepR2, YenR is active only in the absence of the pheromone make by YenI. YenR activates the transcription of a small noncoding RNA called YenS. YenS stimulates the swarming motility of the organism across an agar surface. YenS is opposed by another small RNA called YenT. Y. enterocolitica also encodes another pheromone receptor called YetR, whose functions remain to be described.

In the course of these studies, my lab has published 98 original research articles, 15 review articles, and 12 book chapters. I have edited two books, both on the topic of cell-cell signaling in bacteria. One book was co-edited by Dr. Gary Dunny (University of Minnesota) while the other was co-edited by Bonnie Bassler (Princeton University). I have also organized two ASM conferences that focused on cell-cell communication. I am a member of the American Academy for Microbiology, and have served on several funding panels for the National Institutes of Health and the National Science Foundation.

Teaching Focus

I have three main teaching responsibilities. I teach half of our General Microbiology Lectures (BIOMI 2900), including the central dogma, gene regulation, mutations, and pathogenic microbiology. I teach 100% of Microbiology of Human Contagious Disease (BIOMI 2600). I also teach a graduate level course in bacterial pathogenesis, with an emphasis on critical reading of primary literature.

Selected Publications

Journal Publications

• Winans, S. C., Pinto, U. M., & Pappas, K. M. (2012). The ABCs of plasmid replication and segregation. Nature Reviews Microbiology. 10:755-765.
• Winans, S. C. (2011). A new family of quorum sensing pheromones synthesized using S-adenosylmethionine and Acyl-CoAs (review article). Molecular Microbiology. 79:1403-1406.
• Winans, S. C., Pinto, U. M., Flores-Mireles, A. L., & Costa, E. D. (2011). RepC protein of the octopine-type Ti plasmid binds to the probable origin of replication within repC and functions only in cis. Molecular Microbiology. 81:1593-1606.
• Winans, S. C., Tsai, C., & Chen, C. (2011). Most mutant OccR proteins that are defective in positive control hold operator DNA in a locked high-angle bend. Journal of Bacteriology. 193:5442-5449.
• Tsai, C., & Winans, S. C. (2011). The quorum-hindered transcription factor YenR of Yersinia enterocolitica inhibits pheromone production and promotes motility via a small non-coding RNA. Molecular Microbiology. 80:556-571.
• Winans, S. C., Hao, Y., Glick, B. R., & Charles, T. C. (2010). Identification and characterization of new LuxR/LuxI-type quorum sensing systems from metagenomic libraries. Environmental Microbiology. 12:105-117.

Presentations and Activities

• Bacterial Synchrony. Department of Microbiology seminar. November 2013. University of Minnesota. St. Paul, MN.