Request for Funding

Medical Student Research Fellowship for Summer 2002

Mentor: Perrin C. White, MD
Department: Pediatrics
Room number: G2.236
E-mail: Perrin.White@UTSouthwestern.edu
Project title: Identification of functional role(s) of Very Large G-Protein coupled receptor (VLGR1) using Yeast Two Hybrid Experiments.

Human subjects IRB approved project number (where applicable): N/A

Animal subjects IRB approved project number (where applicable): N/A

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) Basic

Brief Description of Project:
This project is an attempt to further characterize an orphan 7-transmembrane segment (i.e. a putative G-protein coupled) receptor termed Very Large G-protein coupled receptor-1 (VLGR1). At ~6300 amino acid residues, this putative receptor is the largest known cell surface protein. Based on several lines of evidence, we hypothesize that VLGR1 mediates cell-cell interactions that are critical for the development of the vertebrate central nervous system.
As one way to determine the function(s) of VLGR1, we propose to use the yeast two-hybrid system to identify proteins interacting with the VLGR1 cytoplasmic tail. The yeast two-hybrid system, a highly sensitive in vivo transcription based assay, has been used to detect proteins that interact with the C-terminal domains of several other G-protein coupled receptors. The project will involve cloning of sequences encoding the C-terminal domain into a "bait" vector and looking for interactions in yeast with proteins encoded by a pre-existing brain cDNA "prey" library. It may be possible to complete much of this project, at least as far as library screening, over a summer, although confirmatory experiments will likely take longer.

Nikkila H, McMillan DR, Nunez BS, Pascoe L, Curnow KM, White PC. Sequence similarities between a novel putative G-protein coupled receptor and Na+/Ca2+ exchangers define a cation binding domain. Mol Endocrinol 2000, 14:1351-1364.

McMillan DR, Kayes-Wandover KM, Richardson J, White PC. Very large G-protein coupled receptor-1 (VLGR1), the largest known cell-surface protein, is highly expressed in the developing central nervous system. J Biol Chem 2002;277:785-792.

Previous Research Activities or Publications with Medical Students:
Due to scheduling difficulties involving Dr White, the lab head, we have not had many summer students previously. The following represent projects in which other short-stay students or fellows (underlined) participated.

Johrer K, Geley S, Strasser-Wozak EMC, Azziz R, Wollmann HA, Schmitt K, Kofler R, White PC. CYP11B1 mutations causing nonclassic adrenal hyperplasia due to 11?-hydroxylase deficiency. Hum Mol Genet 1997; 6:1829-1834.

Kupari M, Hautanen A, Lankinen L, Koskinen P, Virolainen J, Nikkila H, White PC. Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass and function. Circulation 1998; 97:569-575.

Nunez BS, Lobato MN, White PC, Meseguer A. Functional analysis of four CYP21 mutations from Spanish patients with congenital adrenal hyperplasia. Biochem Biophys Res Commun 1999;262: 635?637.

Kayes-Wandover KM, Schindler REL, Taylor HC, White PC. Type 1 aldosterone synthase deficiency presenting in a middle-aged man. J Clin Endocrinol Metab 2001; 86:1008-1012.

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