A -- Systems Approach to Immunity and Inflammation

RESPONSE DATE IS OCTOBER 31, 2006. As part of its biodefense research mission, the Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID), announces a program to support a systems biology analysis of innate and/or adaptive immune responses to infection, vaccination, or immunotherapy, with a focus on NIAID Category A, B, and C priority pathogens (listed at http://www2.niaid.nih.gov/biodefense/bandc_priority.htm). Immunological research that is not directed specifically at one or more NIAID Category A, B, or C priority pathogen or their products is responsive only if the research: 1) addresses a practical approach to inducing, controlling or improving the effectiveness of innate and/or adaptive immune responses to infection by those pathogens or vaccines or immunotherapies to prevent them; and 2) includes validation studies with at least one NIAID Category A, B or C priority pathogen to confirm the importance of the immunological pathway in protection of the host from, or clearance of that pathogen. The goal of this program is to develop a more comprehensive knowledge of innate and adaptive immune responses to bacteria and viruses or host responses to vaccines and immunotherapeutics against these pathogens, using a systems biology approach. Knowledge gained from these studies will advance our understanding of the delicate balance required to induce protective immunity against infectious agents, in particular NIAID Category A, B, and C priority pathogens, without accompanying immune-mediated damage to the individual. The systems biology analysis shall be based on high-throughput screens of existing or novel mouse models for identification of key regulatory immune response genes, supported by detailed genomics, proteomics, computational biology, and bioinformatics approaches to determine the gene products? functions in innate and/or adaptive immunity to infection with, or vaccination or immunotherapy against, NIAID Category A, B, and C priority pathogens. The systems biology analysis shall include: (1) High-throughput screens of mouse models for identification of key regulatory immune response genes. Forward genetic approaches are preferred for the generation of novel mouse models or study of existing models, since genes can be identified in the absence of a detailed knowledge of the genetic regulation of an observed phenotype. Some recommended genetics approaches include random mutagenesis using ethylnitrosourea (ENU), or large-scale analysis of recombinant inbred strains or congenic animals. More targeted high-throughput methods (e.g., high-throughput generation of targeted Knock-outs, Knock-ins, or deletion mutations) may be utilized with adequate justification of the benefits these approaches bring to large-scale identification of novel immune response genes; and (2) Human correlation studies for analysis of a subset of immune regulatory genes, identified in the mouse studies, in human cell or tissue samples. While human cell lines may be used in initial screens, results shall be validated in primary human cell lines or tissues. The analyses shall be designed to determine whether the immune response genes identified in the mouse function similarly in human immune cells. This RFP will be available electronically on/about June 30, 2006, and may be accessed through the FedBizOpps and the NIAID Office of Acquisitions (OA) Home Page at http://www.niaid.nih.gov/contract. All responsible sources may submit a proposal which will be considered by the agency. This notice does not commit the Government to award a contract. No collect calls will be accepted. No facsimile transmissions will be accepted. See Government-wide Numbered Note 26. Point of Contact Wanda M. Neal, Contract Specialist, Phone 301-451-3685, Fax 301-480-4675, Email wneal@niaid.nih.gov