Office: SCIE 4251
Lab: SCIE 4205
I was introduced to research as a child, through visits to my father's nutritional biochemistry lab at UBC. My first lab job was tending white tailed deer and caribou for a study of Vitamin A deficiency. Those skittish critters enhanced my interest in math and physics! I moved to the University of Victoria after a first undergrad year in Arts and Science at UBC. The new UVic program in Bacteriology and Biochemistry was a positive change after the big intro classes at UBC...including Intro Physics with 499 UBC Engineers! At UVic classes were small and undergrads were treated like grad students - that meant high academic expectations and good interactions with faculty. Single courses in biochemistry, microbiology and molecular biology capped a program rich in organic, physical and analytical chemistry.
Since molecular biology was new and captivating I chose chromatin structure as the topic of my PhD research at the University of Edinburgh... and met my Scottish relatives. Next I accepted a Postdoctoral Fellowship in Leon Heppel's lab at Cornell University, agreed to study membrane transport in Escherichia coli, and found myself immersed in the Great Chemiosmotic Wars! By 1980 most biochemists were convinced that the protonmotive force was a key bioenergetic intermediate. But to understand how a membrane enzyme can be fuelled by protons would require understanding the structures and dynamics of integral membrane proteins - a challenge!
At Cornell and in my lab at Guelph we found that E. coli has multiple transporters for each amino acid, suggesting that each transporter has a distinct physiological role. Students Suzanne Grothe and Tom Redelmeier joined me for my first sabbatical year, in Paul Boyer's lab at UCLA. There we learned how it feels to do sophisticated enzymology on a complex molecular machine: the F0F1-ATPase. Back in Guelph we learned that two proline transporters help E. coli to survive osmotic stress - an important skill for bacteria that survive in water and food as well as human and animal tissues.
Many people now share our interest in cellular osmoregulation because it is important to all living cells, in agriculture and in medicine. But how can a (membrane) protein sense and respond to changes in the osmotic pressure of a solution? How can proline transport be coupled to the protonmotive force and linked to the osmotic pressure? Thanks to Dr. Sandy Kirk, my UVic Phys Chem Prof, we may soon find out...
B.Sc. University of Victoria, B.C., Canada
Ph.D. University of Edinburgh, Scotland
Cells control their own hydration by accumulating and releasing osmolytes, compounds that stabilize cytoplasmic structures and interactions. Multiple osmoregulatory systems have been found in laboratory Escherichia coli strains, but genomic analyses of commensal and pathogenic E. coli predict additional mechanisms. We are identifying new osmolytes and osmolyte transporters, thereby contributing to the structural proteomics of E. coli, seeking new protein-stabilizing osmolytes and defining mechanisms that differentiate pathogenic E. coli from commensal strains.
We use genetic, molecular biological, biochemical and biophysical tools to study E. coli protein ProP. ProP is an osmosensor and osmolyte transporter that detects changes in extracellular osmotic pressure and responds by changing cytoplasmic composition. We were the first to demonstrate that a particular protein (ProP) can act as an osmosensor. ProP is integral to the cytoplasmic membrane of E. coli. We know that it senses changes in extracellular osmotic pressure, but also that such osmotic stress alters many properties of living cells. Our current aims are to understand which change(s) are sensed by ProP and how ProP responds to those changes.
Prof Emeritus Bob Keates creates structural models that facilitate our research on ProP. We collaborate with other labs to better understand the structures of this fascinating protein and the structural dynamics associated with osmosensing and osmoregulation. Our research is supported by Canadians via the Natural Sciences and Engineering Research Council (NSERC) and the Canadian Institutes for Health Research (CIHR).
For more information about my research please see my lab web site
D.E. Culham, M. Meinecke and J.M. Wood (2012) Impacts of the osmolality and the lumenal ionic strength on osmosensory transporter ProP in proteoliposomes. J. Biol. Chem. 287:27813–27822.
J.M. Wood (2011) Bacterial Osmoregulation: A paradigm for cellular homeostasis. Annu. Rev. Microbiol. 65:215-238.
J.M. Wood (2011) Osmotic Stress in Bacterial Stress Response, Second Edition.
G. Storz and R. Hengge, eds. ASM Press, Washington D.C.
S. Chaulk, M.N. Smith–Frieday, D.C. Arthur, D,E. Culham, R.A. Edwards, P. Soo, L.S. Frost, R.A.B. Keates, J.N.M. Glover and J.M. Wood (2010) ProQ is an RNA chaperone that controls ProP levels in Escherichia coli. Biochem. 50:3095-3106.
R.A.B. Keates, D.E. Culham, Y.I. Vernikovska, A.J. Zuiani, J.M. Boggs and JM. Wood (2010) Transmembrane helix I and periplasmic loop 1 of Escherichia coli ProP are involved in osmosensing and osmoprotectant transport. Biochem. 49:8847-56
T. Romantsov, A.R. Battle, J.L. Hendel, B. Martinac and J.M. Wood (2010) Protein localization in Escherichia coli cells: comparison of cytoplasmic membrane proteins ProP, LacY, ProW, AqpZ, MscS, and MscL. J.Bacteriol. 192:912-924.
K. Altendorf, I.R. Booth, J. Gralla, J.-C. Greie, A.Z. Rosenthal and J.M. Wood. 19 November 2009, posting date. Chapter 5.4.5, Osmotic Stress. In A. Böck, R. Curtiss III, J. B. Kaper, P. D. Karp, F. C. Neidhardt, T. Nyström, J. M. Slauch, C. L. Squires, and D. Ussery (ed.), EcoSal—Escherichia coli and Salmonella: cellular and molecular biology. www.ecosal.org. ASM Press, Washington, DC. doi: 10.1128/ecosal.5.4.5
T. Romantsov, L. Stalker, D.E. Culham and J.M. Wood (2008) Cardiolipin controls the osmotic stress response and the subcellular location of transporter ProP in Escherichia coli. J.Biol.Chem. 283:12314-12323.
D.E. Culham, Y.I. Vernikovska, N. Tschowri, R.A.B. Keates, J.M. Wood and J.M. Boggs (2008) Periplasmic loops of osmosensory transporter ProP in Escherichia coli are sensitive to osmolality. Biochem. 47:13584-13593.
T. Romantsov, D.E. Culham and J.M. Wood (2008) Roles of K+, H+, H2O and the membrane potential in solute transport mediated by Major Facilitator Superfamily members ProP and LacY. Biochem. 47:8176-8185.
T. Romantsov, S. Helbig, D.E. Culham, C. Gill, L. Stalker and J.M. Wood (2007) Cardiolipin promotes polar localization of osmosensory transporter ProP in Escherichia coli. Mol Microbiol. 64:1455-1465.
J.M. Wood (2006) Perspective on Osmosensing by Bacteria. Science‚ Science's STKE 357:pe43.
Microbial Adaptation and Development (MICR*3260)
Structure and Function in Biochemistry (BIOC*3560)
Doreen (Culham) Larocque