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

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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