Lipid Regulation of Transient Receptor Potential Channels

Project: Research project

Project Details

Description

Most if not all plasma-membrane ion-channels are influenced by lipid interactions, although few characterized roles for lipid-regulation of ion-channels have been determined. Further, the lipid-binding domains in ion-channels are often cryptic, and not identified by traditional bioinformatics approaches. In this project, studies will be focused on the canonical TRP (TRPC) channels regulate central physiological functions such as neuronal growth cone guidance, vascular tone regulation, and secretion. TRPC channels are activated downstream of G protein coupled receptors and phospholipase C (PLC), yet the exact mechanism of their activation remains obscure. TRPC channels are activated by lipids, yet the mechanisms are unknown. As TRPC channels do not contain conventional lipid binding domains, novel approaches are necessary to identify the structural and functional determinants of TRPC regulation by lipids. The goal of this project is to computationally predict and experimentally verify lipid binding domains within the TRPC family. The core predictive approach that will be utilized within the course of this project is based on structural comparison of functionally related proteins and identifying evolutionary conserved amino acid that dictate the function of the given domain. These predictions will be experimentally validated and assayed for their alteration of (i) channel activity, (ii) channel multimerizaiton, (iii) trafficking, and (iv) protein-protein interactions. The tools and data developed in this project are expected to improve fundamental understanding of ion-channel regulation by lipids.

Broader Impacts: Both Penn State and University of Pittsburgh are dedicated to the education of undergraduate and graduate students. Dr. Patterson, Dr. van Rossum, and Dr. Kiselyov teach cell signaling related undergraduate and graduate courses. The experimental paradigms and principles formulated within this project will be brought into the classrooms to illustrate the development of modern biomedical research.

Dr. Patterson has established a scientific career development graduate course during which the students will directly participate in data analysis, manuscript and grant writing as well as scientific presentations. Dr. Kiselyov and Dr. van Rossum will participate in teaching this class, in particular covering areas of the course, which extend to channel function, plasma-membrane signal transduction, and lyzosomal biology. The present project will provide important experimental and logistical bases for this course. Further, the course will be taught via simulcast to University of Pittsburgh and Howard University and broadcast via YouTube, providing access to anyone interested and incorporated into the University of Pittsburgh-run Supercourse that connects the US educators with students in developing countries. Both lab groups actively recruit undergraduate and graduate students as volunteer and salaried researchers. This project provides an excellent opportunity for undergraduate and graduate student researchers to gain hands-on experience in modern biological research.

StatusFinished
Effective start/end date3/1/092/29/12

Funding

  • National Science Foundation: $250,000.00

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