Notice Number: NOT-AI-10-026
Release Date: April 22, 2010
Receipt Date: July 13, 2010
National Institute of Allergy and Infectious Diseases (NIAID) (http://www.niaid.nih.gov)
Research supported and conducted by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), strives to better understand, treat, and ultimately prevent immunologic, infectious, and allergic diseases The NIAID Division of Allergy, Immunology, and Transplantation intends to issue a Broad Agency Announcement (BAA-NIAID-DAIT-NIHAI2010093) entitled “Nonhuman Primate Major Histocompatibility Complex Gene Discovery and Typing Technology Development”.
NHPs approximate the human in physiology, immunology, and genetics more closely than other animals and, therefore, are often the preferred models to: 1) evaluate the safety and efficacy of candidate vaccines against human pathogens; 2) develop and evaluate immune-based therapeutic strategies to prevent graft rejection and graft versus host disease in cell and organ transplantation; and 3) study the pathogenesis of, and evaluate novel immune-based therapies for infectious and immune-mediated disease.
To support these continuing research efforts the NIAID announces the re-competition of the NHP Major Histocompatibility Complex (MHC) Gene Discovery and Typing Technology Development Program. The objectives of this program are to facilitate and enhance the immunological research conducted with this important model by providing detailed knowledge of NHP MHC genes, loci and alleles through gene discovery and genomic characterization studies; and by developing and providing readily accessible means or methods to genotype individual research animals for the complete set of MHC alleles, or for select alleles, for the optimum design of experiments and genetic management of colonies.
The most commonly used NHP species in immunological and infectious disease research are the Old World NHPs, including the cynomolgus or long-tailed macaque (Macaca fasicularis), the rhesus macaque (Macaca mulatta), the baboon (multiple Papio species), sooty mangabey (Cercocebus atys) and the pigtail macaque (Macaca nemestrina). For purposes of the background information of the NHP MHC below, NHP is used to denote the Old World monkey Macaca sp., unless where otherwise noted.
As in the human genome, the MHC region is the most polymorphic of the NHP genome, with a high degree of genetic diversity across the population. The MHC region includes MHC Class I and II genes, which encode cell surface proteins that serve a critical role in the adaptive immune response. NHP MHC Class I and II orthologs for the Old World macaques exist for most of the human MHC genes. However, a striking difference between the human and the rhesus macaque is that the NHP MHC Class I loci have undergone multiple duplication and expansion events resulting in a significantly greater number of expressed MHC Class I A and B genes per animal than in humans. In addition, the numbers of MHC Class I A and B loci can differ significantly between animals within a population. The NHP MHC Class II region also has been subject to more gene duplication and expansion than its human counterpart. Studies of other macaque species reveal similarly increased MHC genomic complexity over that of humans and great apes.
The NHP MHC Class I and II regions’ genomic organization has had limited detailed characterization, with complete phased genomic sequencing of only two (2) haplotypes of a single rhesus. Due, in part, to the evidence of great variability in the numbers of loci between individual animals, knowledge of the genomic structure from multiple haplotypes and species of NHPs is needed to resolve the MHC organization and facilitate gene discovery efforts. Although progress has been made towards MHC Class I allele discovery for the Indian rhesus macaque, considerable gene, locus, and allele discovery work is still needed for this and most other macaque species and subspecies as are MHC Class II discovery efforts. Coupled with gene discovery is the need to define which genes are expressed, including any conditional or cell/tissue-specific expression patterns, and to establish allele or haplotype frequencies within individual colonies or sources of animals used by the research community.
Identification of the complete set of MHC alleles present in an animal has historically required technically challenging and time- and labor-intensive methods and no certainty that all alleles or loci within an individual were detected. Furthermore, the availability of defined genotyping methods or resources for typing of individual alleles is quite limited compared to the large number of alleles already identified. Development of, and accessibility to, high-throughput technologies for MHC allele genotyping and/or haplotype determination are required to accelerate immunological studies in NHP species. Historically, the variety of DNA-based methods have included: reference strand conformational analysis (RSCA), denaturing gradient gel electrophoresis (DGGE), sequence-specific polymerase chain reaction (PCR-SSP), sequence-specific oligonucleotide probes (SSOP) and MHC-linked microsatellites, or short tandem repeats (STRs). The level and accuracy of information provided and the potential limitations differ by technique.
A variety of DNA-based technologies is required for the diverse needs of the NHP research community, including those methods for specific allele genotyping, haplotyping, and complete MHC genotyping. Affordable methods that are easily upgraded as new allelic or haplotype information becomes available are needed, and, for those methods not provided through resource services, they need to be relatively high-throughput and easily translated to laboratories conducting NHP research.
This solicitation to re-compete the NHP MHC Gene Discovery and Typing Development Program will continue and expand upon the initial program goals to advance the detailed knowledge base of NHP MHC genetic loci, alleles, and haplotypes, and their frequencies; better define the NHP MHC genomic organization; and develop robust, high-throughput genotyping and haplotyping methods.
The NIAID anticipates a single cost reimbursement completion-type award will be made, for a five (5) year period of performance, beginning on or about April 1, 2011. The length of time for which funding is requested should be consistent with the nature and complexity of the proposed research. In no event shall the period of performance proposed by an offeror exceed five 5 years.
All responsible sources may submit a proposal which shall be considered by the Agency. This BAA will be available electronically on/about April 13, 2010, and may be accessed through FedBizOpps http://www.fedbizopps.gov/. This notice does not commit the Government to award a contract. No collect calls will be accepted. No facsimile transmissions will be accepted.
InquiriesDirect inquiries and technical issues to:
Office of Acquisitions, Division of Extramural Activities, NIAID, NIH, DHHS
6700-B Rockledge Drive Room 3214, MSC 7612 (Express mail: Use Zip Code 20817-7612)
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
Office of Extramural
National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
Department of Health
and Human Services (HHS)
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