Request for Funding

Medical Student Research Fellowship for Summer 2004

Mentor: Paul Blount
Department: Physiology
Room number: L4.134
Mail Code: 9040
Phone number: 214 648-8445
E-mail: Paul.Blount@utsouthwestern.edu
Project title: Studying human mechanosensors by using microbial genetics

Human subjects IRB approved project number (where applicable): NA

Animal subjects IRB approved project number (where applicable): NA

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)
This is basic research.

Brief Description of Project:
Human channels have been identified that appear to respond to membrane stretch (e.g. TREK and TRAAK). However, how they sense and respond to membrane tension is unclear. Bacteria contain analogous channels, which help them to survive acute decreases in their osmotic environment. We propose to try to utilize the power of microbial genetics to study the human mechanosensors. We have several bacterial strains that have osmotic- or ionic-dependent phenotypes. We have also recently generated a handful of libraries containing randomly mutated human channels. The project would involve screening these libraries in a variety of ways in order to isolate mutant channels that have altered function. By subsequently characterizing functional properties of the channels and identifying the lesion, we will be able to correlate functional and structural properties, and hopefully will be able to generate and test hypotheses concerning the molecular mechanisms of these channels.

Previous Research Activities or Publications with Medical Students:
In the summer of 2000, Gabriel Rendon utilized microbial genetics to study a suppressor mutation. He found that a "second-site" mutation suppressed many gain-of-function mutations in MscL, a bacterial mechanosensitive channel. Although the results of Mr. Rendon were never published, his work answered a vital question and suggested modifications to our approach. Using these suggested changes, the project was pursued by other researchers in the lab and has led to a manuscript now in press in Molecular Microbiology.

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