SOLICITATION NOTICE
A -- High Throughput Analysis of Gene Expression Patterns in the Nervous System
- Notice Date
- 3/1/2006
- Notice Type
- Solicitation Notice
- NAICS
- 541710
— Research and Development in the Physical, Engineering, and Life Sciences
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Institute of Neurological Disorders and Stroke, 6001 Executive Boulevard, Neuroscience Center, Suite 3287, MSC 9531, Bethesda, MD, 20892-9531
- ZIP Code
- 20892-9531
- Solicitation Number
- NIH-NINDS-06-05
- Response Due
- 4/15/2006
- Archive Date
- 4/30/2006
- Description
- The National Institute of Neurological Disorders and Stroke (NINDS) intends to negotiate a follow-on contract with Rockefeller University (PI: Dr. Nathaniel Heintz, contact # N01-NS-0-2331, awarded 9/30/00) in order to: 1) continue the high-throughput analysis of gene expression patterns in the mouse nervous system during development; and 2) generate new mouse genetic research tools for the scientific community. Using two complementary and coordinated technologies (BAC transgenic reporter mice and standard radiometric in situ hybridization), the contract screens probes for a large number (e.g., thousands) of gene products on a relatively limited number (10 to 20) of sections of the nervous system. Planes of section are chosen by the NINDS to include the structures of most general interest to the neuroscience community (e.g., neocortex, basal ganglia, hippocampus, cerebellum, spinal cord, etc.). The spatial locations/patterns of gene expression are analyzed at 3 or 4 stages of development (early and late embryonic, and early postnatal) and in adult mice. The resulting images of gene expression are digitized and posted in Web-accessible databases, and all BAC transgenic mice generated by the contract are deposited in an NIH-sponsored mouse repository. Background: With the completion of the Human Genome Project, a major focus of biomedical research is to unravel the functions of the ~22,000 genes expressed in the mammalian genome. A crucial and often early step in understanding a gene?s function is to decipher where and when a gene is expressed in an organism, both in normal development and under different physiological and pathological conditions. In neurobiology, the task is even more challenging: the thousands of cell types, the intricate anatomy and elaborate circuitry require sophisticated technologies to reveal patterns of gene expression at a detailed cellular and subcellular level in the nervous system. The systematic and high-resolution mapping of the distribution of genes in specific cells and circuits promises to yield new insights into brain development, function and disease. Of the estimated 15,000-16,000 genes expressed in the brain, fewer than a third have been analyzed to any extent and/or have expression data in the CNS, and only a fraction of these are considered to be well-characterized. Thus, the GENSAT (Gene Expression Nervous System Atlas) contract, awarded to Rockefeller University has developed high-throughput technologies to map the cellular locations of thousands of genes expressed in the mouse CNS throughout development ? i.e., from embryonic to early postnatal ages and into adulthood. GENSAT uses two complementary and coordinated technologies, BAC transgenic reporter mice and standard radiometric in situ hybridization, to create a publicly accessible ?4-dimensional map? revealing the spatial locations and patterns of gene expression throughout the brain and spinal cord over developmental age. As a public resource, all data are posted in Web-accessible databases and all resources including the BAC transgenic mouse lines generated by the contract are deposited in NIH or other public repositories. New Objectives for the GENSAT Follow-on Contract: The current GENSAT contract expires at the end of February 2007, and the NINDS intends to negotiate a follow-on contract with Rockefeller University for an additional five years of funding. Based on the prior successes of the GENSAT project, we expect that the contract will continue to produce outstanding, high-resolution gene expression data on a large scale along with important and powerful new tools for the neuroscience community. For the next 5-year contract period, the NINDS plans to continue to implement the GENSAT contract as described in the Background Section and will initiate requesting performance of the following: 1. Increase the throughput of the BAC transgenic component to ~300 genes per year. This includes a target estimate of approximately 25-50 BAC transgenic lines per year for the creation of state-of-the-art functional genetic tools such as BAC-Cre recombinase ?driver? mice (for conditional cell-specific gene manipulation), and BAC-array mice (a new technology that allows the isolation of mRNA from specific cell populations for microarray gene expression profiling). 2. Increase the throughput of the in situ hybridization (ISH) analysis from 1100 to 1500 genes per year in order to map the expression of ~12,000 nervous system genes by 2012 (the end of the next 5-year contract period). 3. Continue development and implementation of the infrastructure and bioinformatics of the GENSAT contract. This includes i) establishing a multi-site data management and (gene) tracking system for both internal and public use; and ii) adopting more sophisticated bioinformatics approaches (e.g., text-based mining approaches, microarray and other expression screens) to aid in gene selection (particularly of novel genes) for GENSAT. 4. Improve the annotation of the expression data and develop better informatics and/or atlas tools to allow a user easier and enhanced access to the gene expression information in the databases. This includes conducting finer-level annotation of brain regions and/or specific cell-types in the BAC transgenic mice (particularly important with the targeting of cell-type specific BAC vectors) and annotating the locations/levels of gene expression in the major brain structures of the ISH images. Create or implement new brain atlas tools which allow the user to analyze more easily the gene expression images and align/compare the expression images with an annotated (anatomical) Nissl reference atlas. 5. Continue to develop the infrastructure and capabilities to analyze gene expression in other key areas of the nervous system such as the eye and ear and selected peripheral pathways (e.g., DRGs, trigeminal ganglia) in addition to the brain and spinal cord. This includes generating the BAC transgenic mice on another genetic background (for example, backcrossing the FVB/N transgenic founders to C57Bl6) that is less prone to defects of the eye (or ear) to ensure that the nervous system gene expression is the reflection of functioning sensory structures. Technical Requirements: Work under this program requires performance of two interdependent and complementary components for analysis of gene expression in the developing and adult mouse nervous system: Part 1) an initial in situ hybridization (ISH) analysis of large numbers of candidate genes each year; Part 2) a subsequent, more comprehensive analysis of selected genes (generally chosen from the ISH prescreen) in bacterial artificial chromosome (BAC)-EGFP transgenic reporter mice along with the creation of functional genetic research tools for the scientific community. First, using radiometric in situ hybridization technology, the contractor shall prepare and deliver expression data for new candidate genes at a target rate of at least 1500 genes per year for the base contract and each option; each gene shall be analyzed at four developmental ages (E11.5, E15.5, P7 and P42) in the brain, spinal cord and retina of mice. The contractor shall demonstrate the capability of scaling up to a throughput rate of 2500 genes per year if requested by the Government. The ISH screen will be used to guide the selection of candidate genes for subsequent analysis in BAC-EGFP reporter mice. Second, for at least 250 of the 1500 candidate genes analyzed in each Option Year, the contractor shall conduct a more thorough analysis of their cellular locations and patterns of expression in the nervous system of BAC-EGFP reporter mice; each gene shall be analyzed at three developmental ages (E15.5, P7 and P42) in the brain, spinal cord and other selected nervous system structures (as specified by the project officer) of BAC-EGFP mice. The contractor shall demonstrate the capability to increase the gene target throughput rate by 20%, if requested by the Government. From the BAC-EGFP reporter analysis (and as directed by the NINDS and the GENSAT Advisory Panel), the contractor shall target an additional 25 to 50 genes per year for the generation of state-of-the-art functional genetic research tools for distribution to the scientific community (for example, BAC-Cre recombinase ?driver? mice or BAC mice expressing epitope-tagged ribosomal proteins to be used for cell-specific gene expression profiling). For both the ISH and BAC transgenic analysis, the contractor shall annotate all sections for locations and patterns of gene expression, and shall ensure the quality and accuracy of all data and images submitted to the Government under this contract. The contractor is expected to maintain a central data management and (gene) tracking system for all contract and subcontract sites (as may be applicable) as described below, and to develop and implement bioinformatic strategies to assist with gene selection/prioritization for the entire project. Expression images from the contract shall be delivered to the National Center for Biotechnology Information (NCBI) and posted on (or submitted to) other publicly-accessible websites as appropriate. All BAC transgenic mice generated from the contract will be deposited in the UC Davis Mutant Mouse Regional Resource Center (MMRRC) or another national repository as directed by the NINDS. The NINDS believes that the Rockefeller University is the only known source to have the capability for high throughput analysis of gene expression patterns in the mouse nervous system using the technologies and approaches described above and producing outstanding, high-resolution gene expression data that is also consistent and compatible with the data currently in the databases. At the present time, the NINDS is unaware of any other organization, public or private, that has in place existing capabilities that are at the same development and current level of performance (i.e., the equipment, laboratory, animal facilities, technical expertise or professional capabilities) to compete for this requirement, particularly at the quality, consistency and throughput rate stipulated by the contract. Inability to produce high-resolution gene expression data on a large scale would lead to delays in the development of the GENSAT database and incurrence of duplicate costs to get to where we are today, both of which would be unacceptable to the Government. A determination for the use of other than full and open competition has been made in accordance with 41 U.S.C. 253 (c)(1), as set forth in FAR 6.302. The Rockefeller University is considered the only source capable of performing the high throughput analysis and has the prerequisite knowledge and expertise to continue the contract work based on their current experience and work under the contract to date. See Numbered Note 22.
- Record
- SN00996811-W 20060303/060301212009 (fbodaily.com)
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