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

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 试点研究计划的目的是吸引新的研究人员，他们表现出在非人类灵长类动物生物医学研究中发展强大职业或希望在其现有研究计划中添加非人类灵长类动物组成部分的希望。该计划还向研究人员开放，该计划使用非人类灵长类动物的既定研究计划开放，这些灵长类动物希望开发基本的新研究方向。这项研究必须有可能导致对外部资助机构的强大研究赠款申请。试点研究基金不会为既定项目或有资格获得其他来源支持的项目提供临时支持。 四个试点项目正在进行中。 SIV感染的CD8缺失的猕猴中的周围神经病：已获得四只动物，接种了SIVMAC251，并耗尽了CD8+ T细胞。研究的生命阶段已经完成。现在正在分析血液和组织样本。 SIVMAC239的衰减变体的发病机理和神经病生成的遗传决定因素：在7/5/10上被突变的SIVMAC239 SIVMAC239 s/p）感染了突变的SIVMAC239 SIVMAC239 S/P）。根据研究设计，在接种后28天后将两只动物安乐死。我们继续监视剩下的两只动物，以示出SIV疾病进展的迹象。迄今为止获得的数据表明，SIVMAC239 gy s/p比SIVMAC239 gy更具致病性病毒，而SIVMAC239®gy s/p中所产生的突变本质上是补偿性的。 星形胶质细胞是SIV相关炎症的关键调节剂：本季度，我们注意到，在mRNA水平上，对恒星星形胶质细胞的调节，钥匙整合素被降低，尤其是整联蛋白alpha 6。与此相关的是，VCAM-1的增加。实验继续在蛋白质水平上证实这一点。中间丝（包括GFAP，Nestin和波形蛋白）的表达也有所改变。细胞因子的分泌也有一篇论文，部分由该项目资助：MCP-3/CCL7由星形胶质细胞产生：对SIV神经入侵和艾滋病的影响和艾滋病脑炎 猕猴中的体内基因沉默：我们现在收到了所有涉及的调节机构（IACUC，IBC和TRAC）的许可。已将四个Cynomolgus猕猴分配到该项目，目前正在隔离。我们预计将在2011年4月开始MTB感染。虽然我们正在优化猕猴细胞中SOCS3的沉默（骨髓衍生的巨噬细胞），以解决两对最佳的寡核苷酸对，这将使我们有机会执行活动内沉默。 最近授予了其他三个试点项目： 中枢神经系统白质作为Krabbe疾病基因治疗的新型途径 新生儿猕猴的先天免疫力发展 在天然灵长类动物主持人中复制Sylvatic粉丝