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Principal Investigator: Dr. Klaus Beyenbach
Contact Information: E-mail: kwb1@cornell.edu - Phone: 607-253-3482
Sponsor: National Science Foundation
Grant Number: 0542797
Title: Malpighian Tubule Transport Physiology: Mechanism and Regulation
Annual Direct Cost: $134,757
Project Period: 02/15/06-01/31/10
This proposal aims to bring genetics, molecular biology and classical physiology to bear on questions of epithelial transport in Malpighian tubules, the kidneys of insects. Studies of adult mosquito Malpighian tubules in the lab of the principal investigator Beyenbach have uncovered new transport phenomena that stimulate research of epithelial transport in biological systems beyond insects. For example, his finding in Malpighian tubules of a) the energizing of diverse epithelial transport systems with the V-type H+ ATPase and not the Na/K ATPase, b) the channel-like behavior of septate (tight) junctions, and c) the rapid regulation of paracellular permeability in the astonishing time domain of seconds, are motivating searches for similar phenomena in vertebrate tissues. The present proposal is a logical extension of the above findings. Hypothesis-driven experiments promise to discover new transport systems while exploring new ideas in transport physiology. In Aim 1, the functional characterization of NHE8 (a Na-H transport protein) he has already cloned in Aedes Malpighian tubules may uncover the first electrogenic Na/H exchanger in any tissue, vertebrate or invertebrate. Aim 2 applies proteomics, and highly sensitive mass spec methods with the promise of identifying not only NHE8 but also new proteins, and potentially important new transporters in the apical membrane of the adult Malpighian tubule. In Aim 3 he seeks to a) identify gap junctions, b) determine size and charge selectivity, c) explore the role of gap junctions in cell-to-cell transmission of Ca2+ waves that may mediate the signal transduction of leucokinin, and d) test the novel idea of the metabolic, regulation of gap junctions. Three collaborators with an international reputation in molecular biology (Wieczorek), intracellular Ca2+ imaging (Walz), and proteomics (Schooley) have committed their labs to the success of this project. What has motivated this collaboration is the deep understanding that derives from illuminating important research questions from diverse perspectives.
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