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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:
Liu, L., Trimarchi, J.R., Smith, P.J.S. and Keefe, D.L. 2002. Checkpoint for DNA integrity at the first mitosis after oocyte activation. Mol. Repro. Dev. 62: 277-288.
Liu, L., Trimarchi, J., Smith, P.J.S. snd Keefe, D.L. 2002. Mitochondrial dysfunction leads to telomere shortening and genomic instability. Aging Cell. 1: 40-46.
Trimarchi, J.R., Liu, L., Smith, P.J.S. and Keefe, D.L. 2002. Apoptosis recruits two-pore domain potassium channels used for homeostatic volume regulation. Am. J. Physiol. Cell Physiol. 282: C588-C594.
Smith, P.J.S., Haydon, P.G., Hengstenberg, A. and Jung, S.-K. 2001. Analysis of cellular boundary layers: application of electrochemical microsensors. Electrochimica Acta 47(1-2): 283-292.
Smith, P.J.S. and Trimarchi, J.R. 2001. Noninvasive measurement of hydrogen and potassium ion flux from single cells and epithelial structures. Am. J. Physiol. 280: C1-C11. |
