P.hd in Ocular physiologyTata Institute of Fundamental Research
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P.hd in Ocular physiology
We study the mechanisms of transport of small solutes and water molecules across cell membranes. Our primary interest lies in the physiology of epithelial cells, the cells that line surfaces of the body and are the key transporting cells of organs like the intestine, kidneys and eyes. In many of these epithelial cell systems, it is still not clear as to what the driving forces for water absorption and secretion are. The technical challenge of working with small living structures in vitro requires experimental models dedicated to each cell system and the parameters being measured. Where information is sought at a single membrane level we use artificial planar bilayer membranes with model channels like the antibiotic gramicidin inserted in them.
The primary research interest of the Membrane Biophysics Laboratory is the study of transport processes in cell membranes, particularly the coupled transport of solutes and water molecules. We investigate cellular and molecular mechanisms that underlie physiological processes in epithelial cells, cell layers and artificial planar bilayer membranes with model channels inserted in them using three or four techniques:
Microperfusion electrophysiology of tubular insect epithelial cells, e.g. the Drosophila midgut; analysis of ion-currents and ion-water interactions in ion channels in artificial bimolecular lipid membranes; capacitance probe measurement of transepithelial water transport and fluid transport in insect epithelia using the Ramsay technique
The mammalian retinal pigment epithelium is critically required by the neural retina for its nutrition and physiology, and many diseases of the back of the eye like age-related macular degeneration and retinal detachment are thought to have their origins in pigment epithelium and Bruch's membrane dysfunction. One of the main functions of this epithelium is solute-coupled water absorption across the back of the eye. Determination of the small osmotic and hydrostatic gradients that drive fluid transfer across epithelial cell layers by further refinement of the capacitance probe technique will allow us to model solute-coupled water transport in general, and also understand the relative importance of the epithelium and Bruch's membrane water permeabilities. In addition to refining models of intraepithelial solute-solvent coupling, we have shown that the osmotic forces driving water transport in epithelia are much larger than previously believed, and that unstirred-layer corrections are not as large as generally supposed, and certainly tractable.