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 are close to answering that question...
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. 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. ProP is the paradigmatic “osmosensing transporter” because 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 ProP senses changes in extracellular osmotic pressure, and that this response is influenced by the targeting of ProP to the cell poles. Osmotic stress alters many properties of living cells. Now we are learning which change(s) are sensed by ProP and how ProP responds (structurally and functionally) to those changes.
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.
- T. Romantsov, D.E. Culham, T. Caplan, J. Garner, R.S. Hodges and J.M. Wood (2016) ProP-ProP and ProP-phospholipid interactions determine the subcellular distribution of osmosensing transporter ProP in Escherichia coli. Mol Microbiol 103:469-482
- D.E. Culham, I.A. Shkel, M.T. Record, Jr. and J.M. Wood (2016) Contributions of Coulombic and Hofmeister effects to the osmotic activation of Escherichia coli transporter ProP. Biochemistry 55:1301-1313.
- S. Lang, M. Cressatti, K.E. Mendoza, C.N. Coumoundouros, S.M. Plater, D.E. Culham, M.S. Kimber and J.M. Wood (2015) YehZYXW of Escherichia coli is a low-affinity, non-osmoregulatory betaine-specific ABC transporter. Biochemistry. 54:5735-5747.
- C.H. Kerr, D.E. Culham, D. Marom and J.M. Wood (2014) Salinity-dependent impacts of ProQ, Prc, and Spr deficiencies on Escherichia coli cell structure. J. Bacteriol. 196:1286-1296.
- 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.
- 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.
- Romantsov, T. and Wood, J.M. (2017) Contributions of Membrane Lipids to Bacterial Cell Homeostasis upon Osmotic Challenge. In O. Geiger (ed.), Handbook of Hydrocarbon and Lipid Microbiology: Biogenesis of Fatty Acids, Lipids and Membranes. Springer International Publishing AG, Cham, Switzerland, doi:10.1007/978-3-319-43676-0_58-2
- 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.
Microbial Adaptation and Development (MICR*3260)
Structure and Function in Biochemistry (BIOC*3560)
Doreen (Culham) Larocque
The Wood Lab