The purpose of this training grant is twofold: 1. to enhance the research experience of individuals with the Ph.D. degree in the area of cellular and molecular physiology in order to prepare them for academic careers, 2. to provide clinically trained fellows with adequate research training and experience to enable them to carry out independent research in an academic setting. The training objective is to educate four trainees annually in the study of membrane function, more particularly of membrane channels, transporters, pumps and receptors in a wide range of cell types. The research expertise will be acquired through a program lasting one to three years. Research areas cover the molecular and structural biology of membrane proteins, the biophysics of their function, the basic mechanisms whereby ions, water and organic molecules are transferred across biological membranes, the regulation of membrane proteins, the involvement of membranes in signal transduction, the biosynthesis, assembly, intracellular sorting, targeting and insertion of membrane proteins, protein-protein interactions, the signaling pathways in cell regulation and morphogenesis, and the integrated function of cells in epithelia, in whole kidney and transgenic animals. The biological systems being studied include isolated membrane proteins, crystal structures of channels, cDNA clones that encode these proteins, chimeric membrane proteins, mutant transport systems, cytoskeletal elements associated with membrane proteins, specific monoclonal antibodies, membrane fractions and membrane vesicles, liposomes, bilayer lipid membranes, organelles within cells, isolated separated single cells, cellular protoplasts, frog oocytes, symmetrical and polarized cells in culture, epithelial cell sheets in culture, isolated perfused renal tubules, renal tubule segments in situ, isolated epithelia, and transgenic animals. The methodologies which can be acquired though this program cover molecular biological techniques, expression cloning, genetic recombination, in vitro mutagenesis, transfection, expression of membrane proteins, protein isolation and chemistry, microarray assays, reconstitution of membrane components, x-ray crystallography, cryo-electron microscopy, electron- confocal- and fluorescence microscopy, digital video microscopy, immunocytochemistry, atomic force microscopy, molecular probing of membrane components, biosensors and imaging of intracellular composition, cell culturing, patch-clamping, intracellular and transepithelial voltage and conductance measurements, intracellular ion activity measurements, ion fluxes, microdissection, in vitro and in situ microperfusion, as well as kinetic modeling.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Institutional National Research Service Award (T32)
Project #
5T32DK007259-27
Application #
6936463
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
1977-07-01
Project End
2009-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
27
Fiscal Year
2005
Total Cost
$63,047
Indirect Cost
Name
Yale University
Department
Physiology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Lo, Te-Wen; Bennett, Daniel C; Goodman, S Jay et al. (2010) Caenorhabditis elegans fibroblast growth factor receptor signaling can occur independently of the multi-substrate adaptor FRS2. Genetics 185:537-47
Tanis, Jessica E; Bellemer, Andrew; Moresco, James J et al. (2009) The potassium chloride cotransporter KCC-2 coordinates development of inhibitory neurotransmission and synapse structure in Caenorhabditis elegans. J Neurosci 29:9943-54
Chen, L-M; Kelly, M L; Parker, M D et al. (2008) Expression and localization of Na-driven Cl-HCO(3)(-) exchanger (SLC4A8) in rodent CNS. Neuroscience 153:162-74
Lo, Te-Wen; Branda, Catherine S; Huang, Peng et al. (2008) Different isoforms of the C. elegans FGF receptor are required for attraction and repulsion of the migrating sex myoblasts. Dev Biol 318:268-75
Sidani, Shafik M; Kirchhoff, Philipp; Socrates, Thenral et al. (2007) DeltaF508 mutation results in impaired gastric acid secretion. J Biol Chem 282:6068-74
Piermarini, Peter M; Kim, Eugene Y; Boron, Walter F (2007) Evidence against a direct interaction between intracellular carbonic anhydrase II and pure C-terminal domains of SLC4 bicarbonate transporters. J Biol Chem 282:1409-21
Gill, Harindarpal S; Boron, Walter F (2006) Preliminary X-ray diffraction analysis of the cytoplasmic N-terminal domain of the Na/HCO3 cotransporter NBCe1-A. Acta Crystallogr Sect F Struct Biol Cryst Commun 62:534-7
Kirchhoff, P; Andersson, K; Socrates, T et al. (2006) Characteristics of the K+-competitive H+,K+-ATPase inhibitor AZD0865 in isolated rat gastric glands. Am J Physiol Gastrointest Liver Physiol 291:G838-43
Pluznick, Jennifer L; Sansom, Steven C (2006) BK channels in the kidney: role in K(+) secretion and localization of molecular components. Am J Physiol Renal Physiol 291:F517-29
Gill, Harindarpal S; Boron, Walter F (2006) Expression and purification of the cytoplasmic N-terminal domain of the Na/HCO3 cotransporter NBCe1-A: structural insights from a generalized approach. Protein Expr Purif 49:228-34

Showing the most recent 10 out of 19 publications