CATHOLIC HEALTHCARE WEST
Grant: $234,797 - National Institutes of Health - Jul. 16, 2009
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Award Description: Nicotinic acetylcholine receptors (nAChRs) containing the á6 subunit are implicated in diseases ranging from addictions to Parkinson?s disease. These receptors have proved difficult to study using natural sources, due to a combination of scarcity and contamination with other nAChR subtypes. Artificial expression of á6-containing nAChRs would provide a valuable alternative, but obtaining appropriate expression of these complex receptors has been extremely challenging. We propose an approach using linked receptor subunits to make á6- containing nAChRs with properties matching those of their naturally-expressed counterparts, as an alternative to the usual association of individual subunits. This will enforce desired subunit interactions, facilitating expression in a variety of experimentally amenable systems. In turn, this will greatly simplify studies of these important receptors, enhancing knowledge of their properties and helping to guide development of nAChR directed treatments for addictions and Parkinson?s disease.
Project Description: Funding for this project was awarded on August 1, 2009. In the following two months, the project has been assigned an activity number (allowing funds to be spent from the Institute), and personnel assigned. Experimental work has begun. DNA constructs for the alpha6/alpha3 chimeric subunits have been ordered, constructed, and received from GeneArt, Inc. (Burlingame, CA). These DNA constructs are designed to allow substitution for alpha4 subunits in our existing pentameric, and dimer / trimer pair, alpha4beta2 receptor constructs. Large quantities of these concatameric constructs have been made, in preparation for this substitution. Function produced by each of the existing constructs is currently being tested ? this information will guide our choice of which construct(s) will host the chimeric subunits. We will next subclone the chimeric subunits into suitable expression vectors. These vectors will then also be grown in large quantities, providing plentiful material for substitution. The resulting constructs will be sequenced to ensure correct final construction, before functional testing and cloning into our alpha4beta2 concatemer(s) of choice.
Jobs Summary: 'Paul Whiteaker, Ph.D. is the Principal Investigator of this research grant, which supports 25% of his full-time position. Dr. Whiteaker is responsible for overall project oversight, in addition to experimental design and execution, data analysis and interpretation. Ronald J. Lukas, Ph.D. is a Co-Investigator on this project which supports 5% of his full-time position. Dr Lukas shares responsibilities with Dr. Whiteaker for overall project oversight, and will provide technical troubleshooting as necessary. Linda Lucero, M.S. is a senior research assistant in the Whiteaker / Lukas laboratory, and this project provides support for 75% of a full-time position for her. Ms. Lucero has critically important responsibilities on this project, including: maintenance of clonal cell lines, data collection and analysis, partial responsibility for strategic aspects of experimental design and interpretation. As the laboratory's cell culture specialist she is responsible, along with Dr. Whiteaker, for the execution of experiments.' (Total jobs reported: 3)
Project Status: Less Than 50% Completed
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