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Bill McCleary

Associate Professor
Microbiology & Molecular Biology

3128 LSB
Provo, UT 84602

Research Interests

Our lab is currently engaged in research to understand the molecular mechanisms by which the simple bacterium, Escherichia coli senses and responds to changes in environmental phosphate. We are studying this question because it is an extremely useful model to understand complex regulatory schemes in all living organisms. At the heart of this question is a two-component signal transduction system that senses environmental phosphate and controls the expression of many genes for the high affinity acquisition of phosphate and the utilization of alternate sources of phosphorous.

Our current model for the regulalation of this response is that the PstSCAB transporter (a high affinity ABC transporter of Pi) senses Pi levels and communicates through the PhoU protein to the bifunc¬tional histidine kinase, PhoR, which interacts with and controls the steady state phosphorylation level of the response regulator, PhoB. Phospho-PhoB binds to specific DNA sequences upstream of Pho regulon genes, interacts with σ70 and stimulates transcription. Pi sufficiency generates a signal that shuts off the Pho regulon by activating the phospho-PhoB phosphatase activity of PhoR. However, when Pi is limiting or when mutations eliminate any component of the PstSCAB transporter or PhoU, the Pho regulon is turned on. This low Pi signal stimulates the kinase activity of PhoR allowing it to serve as an efficient phospho-donor to PhoB. Phosphate starvation also triggers the general stress response in which cells become increasingly resistant to many environmental stresses. The mas¬ter regulator of this response is σS (RpoS), an alternate sigma factor that com¬petes with σ70 to direct the transcription of genes under its control. The regu¬lation of σS is very complex and has numerous inputs. Its cellular levels are controlled at the levels of transcription, translation, protein turnover and activity.

In the past we have studied the molecular mechanisms of PhoB ac¬tivation and PhoR function. Most of our current research is focused on under¬standing the PhoU protein. We are currently generating mutations in the phoU gene and will be analyzing the protein in the near future to determine its cellu¬lar function and mechanism. We are also studying how the phosphate-sig¬naling pathway feeds into the general stress response of E. coli. We have re¬cently demonstrated that the pstSCAB-phoU message is processed and that one of the pieces interacts with the rpoS message to stimulate its translation.

Memberships

  • American Society for Microbiology (1991 - Present)

Professional Citizenship

  • Officer (specify in Other), American Society for Microbiology (2018 - 2019)
  • Reviewer, Ad Hoc Reviewer, NSF (2016 - 2016)

Courses Taught

Publications

Ramesh K Vuppada Colby R. Hansen Kirsta P.A. Strickland Keilen M. Kelly William Russell McCleary William R. McCleary Stewart G Gardner J. B. Miller Tanner Dean Tanner Robinson McCall Erickson Perry Gene Ridge William Russell McCleary Stewart G Garner Kristine D Johns Rebecca Tanner William Russell McCleary William Russell McCleary

Presentations

Sarah Driggs Bryson Dean Brooke Ernst Keilen Kelly Jacob Wood Stephen Funk William Russell McCleary
Keilen Kelly Bryson Dean Jacob Wood William Russell McCleary
Will Sutherland Keilen Kelly Tanner Robinson William Russell McCleary
Keilen Kelly Tanner Robinson William Russell McCleary
Christopher B. Nielson William Russell McCleary
ravesh K Vuppada William Russell McCleary
Colby Hansen Kirsta Anderson William Russell McCleary
Michael Barrus Jennifer Nguyen Rebecca Tanner William Russell McCleary
William Russell McCleary Stewart G. Gardner
Kristi Strong William Russell McCleary
Stewart G. Gardner William Russell McCleary
William Russell McCleary Kyle Jensen
William Russell McCleary Austin Callison Rachel Brill
Bill McCleary