Version 2.5.2.0

Abstract

Grant Number:	1R21GM075933-01
Project Title:	A chemical genetics approach to improved IMP expression

PI Information:	Name	Email	Title
	HUNT, JOHN F.	jfh21@columbia.edu	ASSISTANT PROFESSOR

Abstract: DESCRIPTION (provided by applicant): High-level production of correctly folded integral membrane proteins (IMP's) remains a major obstacle to their biochemical and biophysical characterization. Expression of prokaryotic IMP'S in E. coli is a "hit-or-miss" proposition, with some expressing welt in native form but most expressing poorly or not at all. Unfortunately, the reasons for success or failure in specific cases are not understood, either in terms of the dependency on the sequence and structural features of the target IMP or in terms of the physiological systems controlling the efficiency of the biogenesis process. The situation for eukaryotic IMP's is even worse, with successful expression in E. coli being equally mysterious but substantially less frequent and the leading alternative expression systems being logistically onerous and generally very costly. In this context, improved methods for IMP expression in E. coli would have great practical value. We propose to use "chemical genetics" to explore a pharmacological approach to improving IMP production in E. coli. A limited set of forensic physiological experiments will be performed on IMP-expressing cells to provide preliminary data on the mechanism of action of active compounds.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
Escherichia coli, bacterial genetics, bacterial protein, chemical genetics, gene expression, membrane protein, technology /technique development
membrane biogenesis

Institution:	COLUMBIA UNIV NEW YORK MORNINGSIDE
	Research Administration
	NEW YORK, NY 100277003
Fiscal Year:	2005
Department:	BIOLOGICAL SCIENCES
Project Start:	23-SEP-2005
Project End:	31-JUL-2007
ICD:	NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
IRG:	ZRG1

---