McCleary, William

Microbiology & Molecular Biology

Email: 4FmppcQgGpiev}Df}y2ihy  (Email Form)

Website: http://mcclearylab.byu.edu/

3128  LSB
Provo, UT 84602
(801) 422-6215

Associate Professor

Curriculum Vitae

 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
 Courses Taught

Fall 2016
  • MMBIO 151: Intro to Microbiology Section 001, 002, 003
  • MMBIO 494R: Mentored Research Section 012
  • MMBIO 695R: Research Section 012
  • MMBIO 699R: Master's Thesis Section 012
Summer 2016
  • MMBIO 494R: Mentored Research Section 011
Spring 2016
  • MMBIO 221: General Microbiology Section 001
  • MMBIO 494R: Mentored Research Section 011
Winter 2016
  • MMBIO 461: Advanced Bacterial Physiology Section 001
  • MMBIO 494R: Mentored Research Section 012
  • MMBIO 695R: Research Section 011

Selected Publications

Journal Articles

Garner SG, Johns KD, Tanner R, McCleary WR. 2014. The PhoU protein from Escherichia coli interacts with PhoR, PstB and metals to form a phosphate-signaling complex at the membrane. Journal of Bacteriology. 196(9):1741-52.  doi:10.1128/JB.00029-14

Book Chapter

McCleary WR. 2017. Molecular Mechanisms of Phosphate Homeostasis in E. coli. Amidou Samie, editor. Escherichia coli. Rijeka: InTech. p. 25

Other

McCleary WR. 2011. The Microbiology Place Website for Brock Biology of Microorganisms, 13/E. San Fransisco, CA: Benjamin Cummings. <website>

Presentations

Barrus M, Nguyen J, Tanner R, McCleary WR. Evidence for protein-protein interactions between PstB and PhoU in the phosphate signaling complex of E. coli. ASM 2012 INTERMOUNTAIN BRANCH MEETING. IDAHO STATE UNIVERSITY. 2012 .

McCleary WR, Gardner SG. PhoU function and membrane interaction. ASM 2012 INTERMOUNTAIN BRANCH MEETING. IDAHO STATE UNIVERSITY. 2012 .

Strong K, McCleary WR. Evidence for protein-protein interactions between PstB and PhoU in the phosphate signaling complex of E. coli. Signal Transduction in Microorganisms. Ventura, California. 2012 .

Gardner SG, McCleary WR. PhoU function and membrane interaction. Signal Transduction in Microorganisms. Ventura, California. 2012 .

McCleary WR, Jensen K. Promoter-swapping as a Tool in the Engineering of E. coli strains for Biological Phosphate Removal. Bacterial Genetics and Ecology (BAGECO 2011). Corfu, gGreece. 2011 .

McCleary WR, Callison A, Brill R. The highly conserved residues of PhoU are involved in membrane localization. Gordon Conference on Microbial Stress Response. Mt Holyoke, MA. 2010 .

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