ENHANCEMENT OF THE PILOT PROGRAM

加强试点计划

• 批准号: 8358185
• 负责人: ANDREW A LACKNER
• 金额: $ 6.84万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358185
• 关键词: Acquired Immunodeficiency Syndrome; Animals; Astrocytes; Attenuated; Award; Biomedical Research; Blood specimen; Bone Marrow Cells; CCL7 gene; CD8B1 gene; Data; Dengue Virus; Development; Disease Progression; Encephalitis; Funding; Funding Agency; Gene Silencing; Genetic Determinism; Glial Fibrillary Acidic Protein; Globoid cell leukodystrophy; Grant; IACUC; Infection; Inflammation; Integrin alpha6; Integrins; Intermediate Filaments; Life; Macaca; Macaca mulatta; Messenger RNA; Monitor; Mutate; Mutation; Mycobacterium tuberculosis; National Center for Research Resources; Natural Immunity; Nature; Neonatal; Neuropathogenesis; Oligonucleotides; Paper; Pathogenesis; Peripheral Nervous System Diseases; Phase; Pilot Projects; Primates; Principal Investigator; Production; Proteins; Qualifying; Quarantine; Research; Research Design; Research Infrastructure; Research Personnel; Research Project Grants; Resources; SIV; Source; T-Lymphocyte; Tissue Sample; United States National Institutes of Health; Variant; Vascular Cell Adhesion Molecule-1; Vimentin; Virus; career; cost; cytokine; gene therapy; in vivo; macrophage; nestin protein; nonhuman primate; novel; programs; research study; white matter

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The purpose of the Pilot Research Program is to attract new investigators who show promise of developing a strong career in nonhuman primate biomedical research or who wish to add a nonhuman primate component to their existing research programs. The program is also open to investigators with established research programs using nonhuman primates who wish to develop substantially new research directions. The research must have potential for leading to a strong research grant application to outside funding agencies. Pilot research funds will not provide interim support for established projects or for any projects that qualify for support from other sources. Four pilot projects are ongoing. Peripheral Neuropathy in SIV-infected CD8-depleted rhesus macaques: Four animals have been obtained, inoculated with SIVmac251 and depleted of CD8+ T cells. The in life phase of the study has been completed. Blood and tissue samples are now being analyzed. Genetic Determinants of Pathogenesis and Neuropathogenesis for an Attenuated Variant of SIVmac239: Four rhesus macaques were infected with a mutated SIVmac239 SIVmac239¿GY S/P) on 7/5/10. Two animals were euthanized at 28 days post inoculation as per the study design. We continue to monitor the two remaining animals for signs of SIV disease progression. Data obtained to date indicates that SIVmac239¿GY S/P is a more pathogenic virus than SIVmac239¿GY and that the mutations made in SIVmac239¿GY S/P are compensatory in nature. Astrocytes are Key Regulators of SIV-related inflammation: This quarter, we have noted that, at the mRNA level, key integrins are down regulated on stellated astrocytes, notably integrin alpha 6. Concomitant with this, there is increased VCAM-1. Experiments continue to confirm this at the protein level. There are also altered expression of the intermediate filaments, including GFAP, nestin and vimentin. Cytokine secretion has also been assessed. We have one paper in press, partially funded by this project: MCP-3/CCL7 production by astrocytes: implications for SIV neuroinvasion and AIDS encephalitis In vivo gene silencing in macaques: We have now received clearance from all the regulatory bodies involved (IACUC, IBC and TRAC). Four cynomolgus macaques have been assigned to the project and are currently in quarantine. We expect to begin Mtb infections in April 2011. Meanwhile we are optimizing the silencing of SOCS3 in macaque cells (bone-marrow derived macrophages) in order to settle on two best pairs of oligonucleotides that will give us a chance to perform in-vivo silencing. Three additional pilot projects were recently awarded: CNS white matter tracts as a novel avenue for gene therapy for Krabbe disease Development of innate immunity in neonatal macaques Replication of sylvatic dengue virus in a natural primate host

这个子项目是利用这些资源的众多研究子项目之一