A -- GENE EXPRESSION PROFILING IN THE NERVOUS SYSTEM FOLLOWING TRAUMATIC SPINAL CORD INJURY

Notice Date

December 18, 2000

Contracting Office

Department of Health and Human Services, National Institutes of Health, National Institute of Neurological Disorders and Stroke, 6001 Executive Boulevard, Nueroscience Center Building, Suite 3287, MSC 9531, Bethesda, MD, 20892-9531

ZIP Code

20892-9531

Solicitation Number

Reference-Number-RFI-NINDS-01-004

Response Due

January 5, 2001

Point of Contact

Kirkland Davis, Chief, Contracts Management Branch, Phone (301) 496-1813, Fax (301) 402-4225, Email kd17c@nih.gov -- Kirkland Davis, Chief, Contracts Management Branch, Phone (301) 496-1813, Fax (301) 402-4225, Email

E-Mail Address

Kirkland Davis (kd17c@nih.gov)

Description

The National Institute of Neurological Disorders and Stroke (NINDS), NIH is seeking to identify sources that are interested to develop capabilities for characterizing gene expression patterns in the mammalian spinal cord following traumatic injury. Introduction and Background The NINDS is the lead government agency for funding of research on spinal cord injury (SCI). Over 250,000 Americans are now paralyzed because of this condition and require specialized care and accommodation for everyday life. Since injury to the central nervous system (CNS) is a very complex phenomenon, research has often been limited to very specific molecules or mechanisms. New technology in the area of molecular biology greatly increases the ability to investigate many changes in gene expression that might occur under this circumstance. Under this solicitation, projects will develop capabilities for characterizing gene expression patterns in the mammalian spinal cord following traumatic injury. Research efforts will employ available neural tissue-specific and/or species-specific cDNA reagents and contemporary high throughput methodologies to quantify expression profiles of genes in acute and chronic phases of SCI. Changes in expression will be characterized at the injury site as well as in areas of the cord rostral and caudal to the lesion site. In addition, regions of brain that represent areas that project to or receive input from the spinal cord will also be evaluated for alterations in gene expression. The injury paradigm will utilize a well-characterized and justified rodent model of spinal cord trauma. Since the CNS is a complex structure, patterns of expression of specific genes will be characterized by in situ hybridization. Precise spatial-temporal expression of genes during development is critical for determining and maintaining the structure and function of the mammalian nervous system. Numerous studies have identified factors that influence cell fate, expression of transmitters or growth factors, and guidance cues for axonal growth and dendritic arborization. These changes may be highly relevant to the adult system after trauma or during disease processes. It is not clear, however, to what extent such developmentally active molecules may be re-expressed after injury or during regeneration. Certainly, the expression of a multitude of genes and gene products associated with neuronal development -- relating to neurite outgrowth, sprouting of fibers, cell survival -- may be affected and changed at critical times after injury. For many years, researchers in the field of SCI have hypothesized that the failure of regeneration in the adult CNS is due primarily to the creation of a hostile "injury milieu"; might changes in expression patterns be correlated with an environment that prevents regeneration? Analysis of changes in the multitude of proteins or mRNA patterns after injury is a daunting task. Up until now, investigators have studied particular proteins (i.e., GAP-43) or classes of proteins (i.e., cytoskeletal proteins, trophic factors) in the hope of finding evidence for involvement in regenerative responses. The development of new technologies to screen large numbers of genes or known sequences for expression after injury may focus the search for the critical elements in acute, sub-acute and chronic stages of injury. Obviously, a complex condition such as SCI has critical temporal and anatomic parameters. Prevention of outgrowth may occur at the injured axon tip or at the cell body. Negative or positive factors are likely expressed from the time of the injury through several stages of recovery and stabilization. Therefore, analysis should include comparative time frames after trauma, and various parts of the neuroaxis that may react differently to the injury, regeneration or stabilization phases. Goals of the Contract 1. Chips and micro-arrays made with cDNA from rodent nervous system (rat and mouse), and from whole animal (mouse) are available, and can be used to create maps of gene expression after SCI. This contract will require the development and application of high-throughput approaches and technologies to quantify expression profiles of genes in rodent spinal cord following trauma. The investigators who undertake the project must understand and have available a relevant rodent model of adult SCI. 2. There will be systematic comparisons of expression patterns for different regions of the cord, as well as at different timepoints following injury. The technology will be applied to at least 6 time points representing acute (hours to days), subacute (days to weeks), and chronic (weeks to months) time windows to capture degenerative, regenerative, or stabilized patterns of reaction to injury. In addition, several different areas will be sampled with respect to the injury site, including areas immediately rostral and caudal to the lesion as well as other segments (i.e., if lesion is at thoracic level sample cervical and lumbar as well). In order to maximize the information gained from the studies, mRNA samples should be collected from relevant regions of the neuroaxis to sample cell bodies of projection neurons (i.e. cortex, brain stem, dorsal root ganglia), as well as local spinal cord circuits. 3. It is not the purpose of this contract to duplicate large scale production of specific chip or array technology at participating centers. Technology should be available for use or purchase. 4. Investigators will be required to provide data on gene expression, localization of gene products or other results of the contract to NIH databases for dissemination. Feedback is sought from the research community on the following: 1. The selection of time points after injury; 2. Levels of sampling; 3. Selection of genes; 4. Methodologies (i.e. SAGE, micro-arrays, etc.) 5. Databasing requirements; and 6. Possible animal models of SCI and control tissues This Request for Information (RFI) is for information and planning purposes only and shall not be construed as a solicitation or as an obligation on the part of the Government. The Government does not intend to award a contract on the basis of responses nor otherwise pay for the preparation of any information submitted or the Government's use of such information. Acknowledgment of receipt of responses will not be made, nor will respondents be notified of the Government's evaluation of the information received. However, should such a requirement materialize, no basis for claims against the Government shall arise as a result of a response to this request for information or the Government's use of such information as either part of our evaluation process or in developing specifications for any subsequent requirement. Responses will be held in a confidential manner. Any proprietary information should be so marked. All respondents are asked to indicate the type and size of your business organization, e.g., Large Business, Small Business, Hubzone Small Business, Small Disadvantaged Business, Women-Owned Business, 8(a), Historically Black College or University/Minority Institution (HBCU/MI), educational institution, profit/non-profit hospital, or other nonprofit organization. Responses should be identified with NINDS RFI No. 01-004, and are due by January 5, 2001. Please submit three (3) copies of your response, not to exceed 5 pages, to the attention of: Laurie A. Leonard, Contracting Officer, Contracts Management Branch, National Institute of Neurological Disorders and Stroke, NIH, 6001 Executive Boulevard, Room 3287, MSC 9531, Bethesda, Maryland 20892-9531. Facsimile (301-402-4225) responses will also be accepted as long as they do not exceed 5 pages in length. E-mail responses, sent to LL44S@nih.gov, will also be accepted.

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Record

Loren Data Corp. 20001220/ASOL008.HTM (D-353 SN5090R2)