Ann H. West

Professor

Assoc VP, Research & Partnerships
Grayce B. Kerr Centennial Chair
E.K. Gaylord Presidential Professor
COBRE Director

Research Areas: Biochemistry, Structural Biology
Email: awest@ou.edu
Phone: (405) 325-1529
Office: SLSRC 2590

Education:
B.S., 1983, Wesleyan University, Middletown, Connecticut
Ph.D., 1991, Yale University, New Haven, Connecticut
Postdoc, 1991-1996, Rutgers University, New Brunswick, New Jersey

Research Keywords:
C. difficile sporulation, two-component signal transduction, stuctural biology, protein phosphorylation

Signal Transduction in Pathogenic Bacteria and Yeast

Two-component systems (TCS) are highly conserved signal transduction pathways found commonly in bacteria, yeast, and plants. In bacteria, TCS are widely recognized as contributing to pathogenesis and virulence. They contain a sensor histidine kinase (HK) and a response regulator (RR) protein. Upon sensing an environmental signal, the HK signals to the RR through transfer of a phosphoryl group. Phosphorylation of the RR shifts the equilibrium between two conformational states of the RR, which in turn modulates its function and stimulates a change (adaptation) in the cell. These pathways represent possible targets for new antimicrobial therapeutic development because they are not present in higher eukaryotes such as mammals. The West group’s long-term goal is to determine global signal-to-response regulatory circuitry in various pathogenic bacteria from sensory HK function to RR-specific gene regulons.

Signal Transduction in Pathogenic Bacteria and Yeast (png)

Phase contrast microscopy images of C. difficile. Mature spores appear phase bright and vegetative cells appear as dark rods

TCS in Clostriodioides difficile

The genome of the hypervirulent strain of Clostridioides difficile (Cd) R20291 encodes 54 HKs and 57 RR proteins comprising TCS pathways that allow the organism to sense and respond (adapt) to environmental changes. The West group embarked on the study of select TCS proteins that play essential roles in antibiotic resistance, spore formation, and virulence in the obligate anaerobe Cd, as part of a collaborative project funded by the Price Family Foundation. Our current projects involve in vivo knockout studies in Cd and in vitro characterization of recently identified TCS proteins implicated in sporulation in Cd. Spores are known to be the major cause of disease transmission to new hosts and are the main source of disease recurrence in patients with C. difficile infections (CDIs).

Sln1-R1 (yellow) and Ssk2-R2 (purple) bind to the same hydrophobic region on Ypd1 (green) with different orientations.

Phosphorelay Signaling Pathway in Saccharomyces cerevisiae

Branched multi-step His-Asp phosphorelay signaling pathways are central to the ability of fungal cells to respond to environmental stress. In the yeast S. cerevisiae, the histidine-containing phosphotransfer (HPt) protein Ypd1 is required for phosphoryl group transfer from Sln1, a membrane-bound sensor hybrid histidine kinase (HHK) to two response regulator (RR) proteins (Ssk1 in the cytoplasm and Skn7 in the nucleus), which mediate osmotic and cell wall stress responses, respectively. The West group studies the role of phosphorylation and dephosphorylation in regulating protein function within the yeast His-Asp phosphorelay signaling pathway. Our X-ray crystallographic studies of the Ypd1 HPt protein in complex with its upstream and downstream receiver domains (Sln1-R1 and Ssk1-R2, respectively), provide an excellent foundation for elucidating the molecular interactions within this phosphorelay signaling system.

COBRE Website Curriculum Vita (pdf)

Awards & Honors

Fellow, American Association for the Advancement of Science, 2021
Grayce B. Kerr Centennial Chair, 2015, University of Oklahoma
Joseph A. Brandt Professorship, 2008, University of Oklahoma
Most Inspiring Faculty Award, 2005, University of Oklahoma Scholar Athlete Banquet
Edith Kinney Gaylord Presidential Professorship, 2001, University of Oklahoma
Irene Rothbaum Award, Outstanding Assistant Professor, 2001, University of Oklahoma College of Arts & Sciences
Cottrell Scholar Award, 1999, Research Corporation
Junior Faculty Research Award, 1997, University of Oklahoma