Emeritus Reader in Cell Biophysics
Research in my laboratory is concerned with the way membrane transport function integrates with other cell processes to regulate the homeostatic behaviour of cells in health and disease. We pioneered the use of integrated mathematical models of cellular homeostasis to predict how cell volume, membrane potential, ionic currents, pH, membrane traffic, osmotic and turgor pressures vary with time in response to environmental changes. The unique predictive power of these models proved critical in elucidating many conflicting or unexplained issues concerned with epithelial cell functions, sickle cell anaemia, malaria-infected red blood cells, plant guard cells and stomatal dynamics.
Current research projects
Modelling cellular homeostasis
A web-based mathematical-computational framework for building models of cellular homeostasis is currently being developed in collaboration with colleagues from Glasgow University. It should be applicable to any cell for which sufficient relevant information is available. It is hoped that such models will serve as fundamental quantitative or semi-quantitative research and teaching tools for biologists, physiologists, biophysicists, and clinical investigators. A web-based model of the homeostasis of human red blood cells is nearing completion.
Modelling the guard cell mechanisms involved in the control of stomatal dynamics
In collaboration with plant physiologists from Glasgow University, we are currently investigating the mechanisms behind the biphasic response of stomata to changes in environmental humidity, and those involved in the rate-control of stomatal opening. Model extensions incorporating the new findings will be applied to explore ways of increasing the water use efficiency of plants and crops.
The pre-invasion stage of malaria parasite invasion of red bood cells
Observations of the invasion process by merozoite forms of Plasmodium falciparum in live cultures under the microscope reveal a process whereby the initial merozoite-red cell contacts trigger vigorous local deformations of the red cell surface, never seen in any other context. These dynamic deformations help reorient the merozoite towards the irreversible apex contact required for invasion, a process usually described as apical alignment. To date, its mechanism remains a mystery, the least understood step of the malaria invasion process.
In collaboration with colleagues from the Physiological Laboratory, , and from the , University of Cambridge, we are attempting to elucidate the biology of this process, alert to the possibility that this knowledge may help expose new targets for prevention or treatments of this endemic disease.
Introductory course on the cell physiology of calcium to third year PDN (PII) students
Ferreira HG, Lew VL, (1976), Use of ionophore A23187 to measure cytoplasmic Ca buffering and activation of the Ca pump by internal Ca, Nature, 259, 47 49
Lew VL, Ferreira HG, Moura T, (1979), The behaviour of transporting epithelial cells. I. Computer analysis of a basic model, Proc. R. Soc. Lond. B. 206, 53 83
Lew VL, Muallem S, Seymour CA, (1982), Properties of the Ca2+ activated K+ channel in one step inside out vesicles from human red cell membranes, Nature, 296, 742 744
Lew VL, Hockaday A, Freeman CJ, Bookchin RM, (1988), Mechanism of inside-out vesiculation of red cell membranes, Journal of Cell Biology, 106, 1893-1901
Lew VL, Tsien RY, Miner C, Bookchin RM, (1982), Physiological [Ca2+]i level and pump leak turnover in intact red cells measured using an incorporated Ca chelator, Nature, 298, 478 481
Lew VL, Hockaday A, Sepulveda MI, Somlyo AP, Somlyo AV, Ortiz OE, Bookchin RM, (1985), Compartmentalization of sickle cell calcium in endocytic inside out vesicles, Nature, 315, 586 589
Lew VL, Bookchin RM, (1986), Volume pH and ion content regulation in human red cells: analysis of transient behaviour using an integrated mathematical model, Journal of Membrane Biology, 92, 57 74
Lew VL, Freeman CJ, Ortiz OE, Bookchin RM, (1991), A Mathematical Model on the Volume, pH and Ion Content Regulation in Reticulocytes. Application to the Pathophysiology of Sickle Cell Dehydration, Journal of Clinical Investigation, 87, 100-112
Lew VL, Tiffert T, Ginsburg H, (2003), Excess hemoglobin digestion and the osmotic stability of Plasmodium falciparum-infected red blood cells, Blood, 101,4189-4194
Lew VL, Bookchin RB, (2005), Ion transport pathology in the mechanism of sickle cell dehydration, Physiol. Rev. 85, 179-200
Mauritz JMA, Esposito A, Ginsburg H, Kaminski CF, Tiffert T, Lew VL, (2009), The homeostasis of Plasmodium falciparum-infected red blood cells, PLoS Computational Biology, 5, e1000339
Hills A, Chen Z, Amtmann A, Blatt MR, Lew VL, (2012), OnGuard, a computational platform for quantitative kinetic modelling of guard cell physiology, Plant Physiology, 159(3), 1026-1042
Crick AJ, Tiffert T, Shah SM, Kotar J, Lew VL, Cicuta P, (2013), An automated live imaging platform for studying merozoite egress-invasion in malaria cultures, Biophys. J., 104, 997-1005
Crick AJ, Theron M, Tiffert T, Lew VL, Cicuta P, Rayner JC, (2014), Quantitation of malaria parasite-erythrocyte cell-cell interactions using optical tweezers, Biophys. J. 107:846-853
Tiffert T, Lew VL, (2014), Dynamic morphology and cytoskeletal protein changes during spontaneous inside-out vesiculation of red blood cell membranes, Pflugers Arch - Eur J Physiol. DOI 10.1007/s00424-014-1483-5
Lew VL, Tiffert T, (2015), Volume control in Plasmodium falciparum infected red blood cells, Encyclopedia of Malaria, (Springer), 2015, DOI 10, 1007/978-1-4614-8757-9_27-1