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The transport of molecules across the plasma membrane of cells can create interesting and sometimes unexpected boundary conditions. Measuring these phenomena can provide direct insight into the underlying cell physiology by monitoring the net activity of specific transporters, such as pumps, porters, and channels, or the diffusion gradients of soluble molecules. These measurements can, however, be difficult but become possible with the application of self-referencing and near field optical methods. This laboratory, part of the BioCurrents Research Center (NCRR) and resident program in cell biology, takes advantage of these techniques to work on the physiology of membrane transport.
Physiological studies have been undertaken on diverse systems, frequently in collaboration with visiting scientists. Notably, hydrogen ion gradients surrounding transporting epithelia have been described in several preparations and the underlying mechanisms studied with the aid of pharmacological and immuno-histochemical tools. Of particular interest has been the physiology of the vacuolar-type proton ATPases and associated transporters. Oxygen gradients surrounding neurons and single cells are currently being described, as is the release of nitric oxide. Work is also in progress on the physiological and molecular adaptations of extremophiles to acidic environments.
This laboratory is also investigating the development of self-referencing biosensors with initial success already achieved in the detection of glucose and glutamate. Hybrid sensors, combining optical recording methods with ion-selective and electrochemical probes are also under development, allowing a more accurate correlation of cellular responses by collateral signal detection. Parts of this study are being conducted in collaboration with Stefan McDonough.
Senior Scientist Peter J. S. Smith
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Education:
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| 1991 |
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M.A. Neurobiology, Univ. of Cambridge, England |
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| 1980 |
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Ph. D. Physiology, Univ. of Aberdeen, Scotland |
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| 1976 |
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B.S. Zoology, Univ. of Aberdeen, Scotland |
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Recent Publications:
Winnie Wai Chi Shum, Nicolas Da Silva, Mary McKee, Peter J.S. Smith, Dennis Brown and Sylvie Breton Transepithelial projections from basal cells are luminal sensors in pseudostratified epithelia. Cell in press
Pethig, R., Menachery, A., Heart, E., Sanger R.H. and. Smith, P.J.S. (2008). Dielectrophoretic assembly of insulinoma cells and fluorescent nanosensors into three-dimensional 'pseudo-islet' constructs. IET Nanobiotechnology. 2(2): 31-38.
Li, H., Chen, Y., Jones, A.F., Sanger, R.H., Collis, L.P., Flannery, R., McNay, E.C., Schwartzenbacher, R., Bossy, B., Bossy-Wetzel, E., Bennett, M.V.L., Pypaert, M., Hickman, J.A., Smith, P.J.S., Hardwick, J.M. and Jonas, E.A. (2008) The anti-apoptotic protein BCL-xL controls synapse formation. PNAS 105(6): 2169-2174.
Nuccitelli, R. Nuccitelli, P. , Ramlatchan, S., Sanger, R. and Smith, P.J.S. (2008). Imaging the electric field associated with mouse and human skin wounds. Wound Repair and Regeneration. 16 (3): 432-441.
Messerli, M.A., Kurtz, I. and Smith, P.J.S. (2008) Characterization of Optimized Na+ and Cl- liquid membranes for use with extracellular, self-referencing microelectrodes. Anal. Bioanal. Chem. 390(5): 1355-9.
Smith, P.J.S., Sanger, R.S. and Messerli, M.A. (2007) Principles, Development and Applications of Self-Referencing Electrochemical Microelectrodes to the Determination of Fluxes at Cell Membranes. In: Methods and New Frontiers in Neuroscience. Ed. Adrian C. Michael. CRC Press. Chapter 18
Gray, J.P., Heck, D.E., Mishin, V., Smith, P.J.S., Hong, J.Y., Thiruchelvam, M., Cory-Slechta, D.A., Laskin, D.L., and Laskin, J.D. (2007) Paraquat increases cyanide-insensitive respiration in murine lung epithelial cells by activating an NAD(P)H: Paraquat Oxidoreductase: Identification of the enzyme as thioredoxin reductase. J. Biol. Chem. 282(11): 7939-49.
Kreitzer, M.A., Collis, L.P., Molina, A.J.A., Smith, P.J.S., Malchow, R.P. (2007) Modulation of extracellular proton fluxes from retinal horizontal cells of the catfish by depolarization and glutamate. Journal of General Physiology. 130: 169-182.
Heart, E. and Smith, P.J.S. (2007) Rhythm of the beta-cell oscillator is not governed by a single regulator: Multiple systems contribute to oscillatory behavior. Am J Physiol Endocrinol Metab. 292(5):E1295-300
Heart, E., Yaney, G., Corkey, R.F., Schultz, V., Luc, E., Liu, L., Deeney, J.T., Shirihai, O., Tornheim, K., Smith, P.J.S, and Corkey, B.E. (2007) Ca2+, NAD(P)H and membrane potential changes in pancreatic betacells by methyl-succinate: comparison with glucose. Biochem J. 403(1):197-205.
Messerli, M.A., Corson, E.D., and Smith, P.J.S. (2007) Measuring Extracellular Ion Gradients from Single Channels with Ion-Selective Microelectrodes. Biophysical J. 92(7): L52-54.
Da Silva N., Shum W.W. C, El-Annan J., Paunescu T.G., McKee M., Smith P.J.S, Brown D., Breton S. (2007) Relocalization of the V-ATPase B2 subunit to the apical membrane of epididymal clear cells of mice deficient in the B1 subunit. Am. J. Physiol: Cell Physiology. 293(1):C199-210. |
