The projects of the program project were dependent on the production of viral vectors and molecular biological services provided by the Molecular Analysis Core, previously funded as part of Institutional Core grant 5P30HD04147 from NICHD. That was not renewed, with the result that all core services effectively ceased on July 31, 2001. Thus, the program project investigators no longer have the services that they relied upon when their original grants were written and budgets prepared. Budgets for these projects are modest (averaging approx. $125K in direct costs per project for the current year), and the unavailability of core services and central supplies has resulted in a correspondingly large impact on the ability of investigators to meet their originally specified goals. This supplement is required to restore those services that are essential for the completion of the goals of the project. Specifically: (1) To produce well-characterized, high quality stocks of adenoviral and herpes viral amplicon vectors, expressing transgenes relevant to individual projects; (2) To provide centralized PCR-mediated screening of transgenic mice for founder identification and line maintenance; and (3) To administer the buying in bulk and distribution of common supplies. Viral vectors are essential for the completion of Projects I, II, III, and IV. The establishment of a centralized core providing virological expertise is necessary to provide investigators unfamiliar with these techniques access to this state-of-the-art technology. The loss of time, resources, and productivity that would result if all individual investigators were required to equip their laboratories for vector production and become proficient in producing high titers of well-characterized viral vectors, would have a devastating effect on the ability of investigators to complete their stated goals in a reasonable amount of time. Additionally, centralized production of viral stocks allows monitoring of the quality of these preparations, thus producing consistent high titer stocks, flags any problems associated with certain transgenes, and encourages a sharing of reagents among members of the Program. Projects I, II, III, and V are also reliant on the production and use of well-characterized transgenic and knockout strains of mice. The testing of transgenic mice for founder identification and/or maintenance also was part of the Institutional Core Grant (not renewed), and consequently consumes a large unanticipated amount of time and resources for these projects. Including these services within a central core would not only be more efficient when carried out in batches by a single individual skilled in DNA extraction and PCR analysis than by multiple different individuals, but would also free time and resources for investigators to devote themselves to the unique aspects of their projects, as originally planned. Finally, all projects can accomplish more from the same grant dollars expended through the use of molecular biological and tissue culture reagents bought in bulk and distributed centrally, as reflected by the modest budgets of the original application.
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