ANNOUNCEMENT OF NINDS HIGH THROUGHPUT DRUG SCREENING SERVICE AND CALL FOR ASSAY PROPOSALS RELEASE DATE: November 14, 2002 NOTICE: NOT-NS-03-004 National Institute of Neurological Disorders and Stroke (NINDS) (http://www.ninds.nih.gov) The National Institute of Neurological Disorders and Stroke announces the availability of a new service for neurodegeneration investigators. NINDS has established a high throughput drug screening (HTS) service facility, located at Southern Research Institute in Birmingham, Alabama. The goals of this program are to assist researchers in identifying new compounds that will be valuable as research tools and drug leads. In addition, this program will evaluate the promise of assays for use in HTS drug discovery efforts. Southern Research will adapt laboratory assays of neurodegeneration into automated formats and use them to test a collection of approximately 100,000 chemically diverse, non-proprietary compounds. Assays will be provided by investigators in the neurodegeneration research community. The data from the screens will be made available to the investigators for further evaluation and follow up studies. This is an opportunity for researchers with robust and reproducible assays of neurodegeneration to have their assays screened in a high throughput setting. The data derived from individual screens will also be assembled into a central NINDS database and analyzed for commonalities among assays. More information on this program is available at http://www.ninds.nih.gov/funding/areas/technology_development/HTS_Facility.htm. The NINDS is now accepting proposals for neurodegeneration assays to be automated and used in compound screens at the Southern Research HTS facility. The types of assays sought and instructions for applying to the program follow. SCOPE Assays proposed for this service should represent mechanisms associated with neurodegenerative diseases, including ALS, Parkinson's Disease, Spinal Muscular Atrophy and triplet repeat disorders such as Huntington's Disease. The goals of the proposed screens may be drug discovery or studies of neurodegeneration mechanisms. Assays may involve proteins, cells or simple model organisms. Appropriate assays include but are not limited to: o Toxicity of disease-causing proteins in neuronal cell lines or primary neuronal cultures. o Toxicity of disease-causing proteins in yeast or other simple model organisms. o Modulation of expression of disease-causing or neuroprotective genes, including effects on transcription, splicing or translation. o Cell-based assays of activity, processing or turnover of disease- causing or neuroprotective proteins. o Biochemical assays of activity of disease-causing or neuroprotective proteins. Assays should be sufficiently developed to demonstrate reproducibility in a low throughput setting and should be feasible for adaptation to an automated, high throughput screening approach. For example, it should be possible to reduce the assay to a 96-well format. Demonstration of feasibility may include: o Demonstration of highly predictable and reproducible responses to appropriate experimental controls and/or pharmacological standards. o Demonstrated selectivity and reproducibility of response to a small but diverse collection of compounds, such as a collection of FDA approved drugs. There should be a clear and feasible plan for evaluating the significance of the hits obtained in the primary screen, including the use of secondary screens for identifying artifacts. The overall goals of the screening project should be well defined and clearly presented. For a proposal to be competitive, it will be critical to provide evidence of a serious intent to follow up the results of the assay development and compound screens conducted within this program. This may include a demonstration of plans to use the modified assay in a further drug development effort outside the contract, to chemically optimize identified compounds for use in drug discovery, or to use the compounds as tools in a well-defined research program. Letters of intent to collaborate or consult should be provided in areas outside the expertise of the principal investigator. MECHANISM OF SUPPORT NINDS will cover the costs of assay automation and screening through the contract with Southern Research. This will include the cost of travel of investigators to Southern Research to convey specifics of assay design and interpretation to Southern Research scientists. Investigators will receive no additional financial support through this mechanism. HOW TO APPLY Submission of proposals should be made electronically. Send an Email message to HTSassays@ninds.nih.gov with the PI's name (last name, first name) on the subject line. Include the following sections in an attached file in MSWord or WordPerfect format: 1) A cover page citing this NOTICE and including the title of the assay, PI name, and address, phone and email information for the PI. 2) An abstract. 3) A two to five page proposal describing the assay, feasibility for adaptation to HTS, mechanisms for secondary screening of HTS hits and plans for future studies based on the screening results. 4) Any letters of collaboration or consultation should also be submitted electronically. REVIEW PROCEDURE Applications appropriate to this solicitation will be reviewed by the NINDS HTS Facility Steering Committee. This committee will include scientists from academia, industry and the NINDS. Review criteria will include: o significance of the disease model for neurodegeneration o quality of the assay design o feasibility of adapting the assay to HTS format o quality of the plan for secondary evaluation of the compounds identified by HTS o long-term goals for the use of the assay and the compounds identified by HTS SELECTION CRITERIA NINDS will select approximately three assays per year to be screened at the facility. We expect to receive more high quality applications in response to this announcement than can be accepted. Thus, the selection process will be competitive. Criteria for the selection of individual assays will include: o Scientific Merit (as determined by peer review according to the criteria above) o Programmatic Priorities o Capacity of NINDS Facility Receipt deadline: January 31, 2003 (future receipt dates will be announced in the NIH Guide) Review date: February/March 2003 Applicants will be notified of the decision by March 31, 2003. Applicants will not receive information relating to the review of their application. All applications will be considered strictly confidential, and unsuccessful applications will not be retained. Inquiries: Dr. Jill Heemskerk Program Director, Technology Development Tel: 301-496-1779 Email: jill_heemskerk@ninds.nih.gov
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