[Federal Register Volume 64, Number 27 (Wednesday, February 10, 1999)]
[Notices]
[Pages 6667-6668]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-3237]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


National Institute of Environmental Health Sciences: Opportunity 
for a Cooperative Research and Development Agreement (CRADA) for 
Development of Technology and Application Testing of Toxicological cDNA 
Microarrays

AGENCY: National Institute of Environmental Health Sciences, National 
Institutes of Health, PHS, DHHS.

ACTION: Notice.

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SUMMARY: The National Institutes of Health (NIH) seeks an agreement 
with a company(s) which can pursue the development of technology and 
application testing of toxicological cDNA microarrays for analysis of 
exposed human and mouse biological samples. The National Institute of 
Environmental Health Sciences (NIEHS) is in the first phases of 
developing and testing this technology for application to human 
toxicology. A CRADA for the co-development of technology or testing of 
this new toxicology assay will be granted to the awardee(s).

DATES: Capability statements must be received by NIH on or before April 
12, 1999.

ADDRESSES: Proposals and questions about this opportunity may be 
addressed to Dr. J. Carl Barrett, Scientific Director, NIEHS, Mail Drop 
C2-15, P.O. Box 12233, Research Triangle Park, NC 27709; Telephone 
(919) 541-2992; Fax (919) 541-7784; E-mail [email protected]

SUPPLEMENTARY INFORMATION: cDNA microarrays are tools that can be used 
to analyze changes in genome-wide patterns of gene expression. This 
technology may potentially revolutionize the way toxicological problems 
are investigated. The main challenges facing investigators in 
environmental health research is to assess exposures and identify 
hazards. Defining the mechanisms of action of environmental agents can 
greatly assist in hazard identification, species extrapolation, and 
risk assessment. Given that exposures to different classes of toxicants 
result in distinct patterns of altered gene expression, microarray 
technology can be utilized to categorize and classify these effects. In 
defined model systems, treatment with known agents, such as polycyclic 
aromatic hydrocarbons, dioxin-like compounds, peroxisome proliferators, 
oxidant stress, or estrogenic chemicals may provide a gene expression 
signature on a microarray which represents the cellular response to 
these agents. These same systems can then be treated with unknown, 
suspect agents to determine if one or more of these standard signatures 
is elicited. This approach will also help elucidate an agent's 
mechanism of action and may also be used to detect changes in exposed 
human populations, information essential for the risk assessment 
process. cDNA microarrays could also be used to potentially determine 
cross-talk between combinations of agents (i.e. dioxin and estrogen). 
Microarray technology could in the long run, provide a relatively 
inexpensive, quick way to screen for potential bio-reactive agents.
    We are in the process of establishing cDNA microarray technology at 
the NIEHS. Currently, we are developing custom DNA chips that are human 
cDNA clone subarrays oriented toward the expression of genes involved 
in responses to toxic insult. These include xenobiotic metabolizing 
enzymes, cell

[[Page 6668]]

cycle components, oncogenes, tumor suppressor genes, DNA repair genes, 
estrogen-responsive genes, oxidative stress genes, and genes known to 
be involved in apoptotic cell death. This technology is in 
developmental stages at NIEHS, and we are interested in establishing 
relationships with CRADA partners to further our efforts on technology 
development and application toward toxicology research.
    NIEHS seeks partnerships for collaboration in the development of 
arrayed cDNA libraries from various tissue sources, the development of 
toxicology models to test/validate the use of microarray technology in 
toxicology testing, and the development of bioinformatics support 
involving pattern recognition and classification.

Roles of NIEHS

    1. Provide project coordination for overall project development and 
testing.
    2. Establish various classes of toxicology gene expression arrays 
and subarrays based on existing data from toxicology studies or 
specific cDNA libraries.
    3. To manufacture DNA chips from provided DNA sets and arrayed 
libraries, label and hybridize RNA probes to the expression arrays, and 
scan data and analyze and compile results.
    4. To validate methods and expression array patterns using probes 
generated from established toxicology exposure models that have been 
developed by NIEHS or CRADA partner(s).

Role of the CRADA Partner(s)

    1. Provide cDNA libraries from rodent and human sources that may be 
compatible for use to generate targets for use in synthesis of gene 
chips. May include custom cDNA library isolation from a variety of 
species and tissue sources.
    2. Provide clone arrays from cDNA libraries from rodent and human 
sources, including arrays from custom, tissue-specific cDNA libraries. 
Also includes the sequence validation of arrayed clones.
    3. Provide RNAs from traditional toxicology assays/models for use 
in validation testing of the use of microarray in toxicological 
identification/exposure assessment.
    4. Provide bioinformatics/database support to subarray development 
and compilation and analysis of data, including pattern recognition 
from expression analyses experiments.
    Selection criteria for choosing the CRADA partner(s) will include, 
but will not be limited to, the following:
    1. Experience in the generation of high quality cDNA libraries, 
including custom and subtractive libraries. Ability to array cDNA 
libraries and provide resources to sequence-validate library clones.
    2. Experience in toxicology testing models and ability to provide 
high quality and quantity RNA from these models.
    3. Experience in database management and the development of 
software for the analysis of pattern recognition. May also include 
plasmid purification and PCR amplification of DNA from existing sub-
arrayed library sets.

    Dated: February 1, 1999.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer.
[FR Doc. 99-3237 Filed 2-9-99; 8:45 am]
BILLING CODE 4140-01-M