Project 002 - VIDI
项目 002 - VIDI
基本信息
- 批准号:10602744
- 负责人:
- 金额:$ 67.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-01 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:AntigensArchitectureAreaAutopsyBindingBiological AssayBloodCCR6 geneCD4 Positive T LymphocytesCellsCessation of lifeChromatinClonal ExpansionData AnalysesData SetDetectionEffector CellEnvironmentEnvironmental Risk FactorEpigenetic ProcessFamilyFire - disastersGenesGenetic TranscriptionGenomeGiftsGoalsHIVHIV InfectionsHomeHuman bodyImageImaging technologyImmuneImmunologyInflammationIntegration Host FactorsInterruptionIntrinsic factorInvestigationKnowledgeLymphoid TissueMapsMicroscopyMucous MembraneNatural Killer CellsPenetrationPersonsPharmaceutical PreparationsPharmacologyPhasePhenotypePlasmaPopulation DynamicsPopulation ProcessPredispositionProcessProvirus IntegrationProvirusesResearch Project GrantsResource AllocationRunningSamplingScienceShockSiteSourceSpecimenSurfaceTechniquesTechnologyTissuesViralViral PhysiologyViremiaVirusadaptive learningantiretroviral therapybrain tractcohortcomorbidityend of lifehigh dimensionalityimprovedin vivoinflammatory milieuinnovationinsightinterestpharmacologicprogrammed cell death protein 1programsreproductive tractsingle cell technologysocial stigmasuccesstherapeutic targetviral rebound
项目摘要
PROJECT 2. Viral Immunology, Drugs, and Imaging (VIDI) Research Project - ABSTRACT
Despite the success of antiretroviral therapy (ART) improving the lives of persons with HIV (PWH), curing HIV
would be important to reduce stigma and long-term co-morbidities associated with HIV infection that occur even
during ART. Developing a successful cure will need to better identify the viral and host factors that govern HIV
dynamics in its HIV Obligate MicroEnvironment (HOME) to identify reservoir vulnerabilities that can be targeted.
The Viral Immunology, Drugs, and Imaging (VIDI) Research Project (RP) will focus on immune, pharmacological,
host epigenetic cellular environments, and tissue architecture that govern the continuum of HIV reservoir
dynamics. This characterization by the VIDI RP alone will add considerable new knowledge to the field. In the
HOME program, these assay results will be integrated with viral features of HIV reservoir dynamics characterized
by VENI RP, and all datasets will be further integrated and analyzed by VICI RP.
For experimental planning, the HIV reservoir dynamic continuum is simplified as the following reservoir states:
· Leaves HOME when HIV (re)activates from tissues during antiretroviral therapy (ART) (i.e., like packing its
bag and getting ready to leave) and causes rebound viremia during ART interruption.
· Comes HOME when HIV (re)populates tissues during viremia off ART and through the spread of clonally
expanded HIV-infected cells while on ART. (Clonal expansion is like adding family to the home.)
· Stays HOME when HIV (silently) persists in blood and tissue reservoirs (on and off ART).
To optimize allocated resources, we developed a two-step Adaptive Learning Approach. During the Mapping
phase, the VIDI RP will examine how cellular and soluble inflammatory milieus and ART levels are associated
with each reservoir state (i.e., leaving, coming, staying). The VICI RP will assist in the integration and analysis
of these data to identify ‘samples-of-interest’ that have pre-defined reservoir states and sufficient cellular
environment for deeper investigation. In the Confirmation phase, the VIDI RP will use single-cell and imaging
technologies to further characterize environmental factors associated with reservoir dynamics at a deeper level.
Importantly, the feasibility of our VIDI RP is greatly enhanced by the knowledge gained from our previous P01
(AI131385) and its Last Gift Cohort, which collects pre- and post- mortem specimens from PWH who did (n=5)
or did not stop ART (n=15) before death. The HOME program will allow the continuation of this cohort while
expanding the science to study HIV dynamics across the human body at the single-genome and single-cell level.
In summary, the overall HOME program will provide a deep delineation of environmental factors governing HIV
reservoir dynamics, which is directly responsive to the Understanding HIV Reservoir Dynamics RFA AI-21-013.
This new knowledge will inform HIV cure strategies aiming at reversing latency (“Shock and Kill”) or at silencing
permanently deep reservoirs (“Block and Lock”) and provide new insights in ways to reduce local HIV-associated
tissue damage, which has been implicated in inflammation-related illnesses.
项目 2. 病毒免疫学、药物和成像 (VIDI) 研究项目 - 摘要
尽管抗逆转录病毒疗法(ART)取得了成功,改善了艾滋病毒感染者(PWH)的生活,治愈了艾滋病毒
对于减少与艾滋病毒感染相关的耻辱和长期合并症非常重要,这些疾病甚至发生在
ART 期间。开发成功的治疗方法需要更好地识别控制艾滋病毒的病毒和宿主因素
其 HIV 义务微环境 (HOME) 的动态变化可识别可针对的病毒库脆弱性。
病毒免疫学、药物和成像 (VIDI) 研究项目 (RP) 将重点关注免疫、药理学、
宿主表观遗传细胞环境和控制 HIV 储存库连续体的组织结构
动力学。仅 VIDI RP 的这种表征就将为该领域增添大量新知识。在
HOME 计划中,这些检测结果将与 HIV 病毒库动力学特征相结合
由 VENI RP 提供,所有数据集将由 VICI RP 进一步整合和分析。
对于实验规划,HIV 储存库动态连续体被简化为以下储存库状态:
· 在抗逆转录病毒治疗 (ART) 期间,当 HIV 从组织中(重新)激活时离开家(即,将其打包)
包并准备离开)并在 ART 中断期间导致病毒血症反弹。
· 当 HIV 在 ART 后的病毒血症期间以及通过克隆性传播在组织中(重新)繁殖时,您就回家了
在 ART 期间扩增了 HIV 感染细胞。 (克隆扩张就像在家里增添家人一样。)
· 当艾滋病毒(默默地)持续存在于血液和组织储存库中时(无论是否接受抗逆转录病毒治疗),请待在家里。
为了优化分配的资源,我们开发了一种两步自适应学习方法。测绘期间
阶段,VIDI RP 将检查细胞和可溶性炎症环境与 ART 水平之间的关系
每个水库状态(即离开、到来、停留)。 VICI RP 将协助整合和分析
这些数据来识别具有预先定义的储存状态和足够的细胞的“感兴趣的样本”
进行更深入调查的环境。在确认阶段,VIDI RP 将使用单细胞和成像
进一步表征与更深层次的油藏动态相关的环境因素的技术。
重要的是,我们从之前的 P01 中获得的知识大大增强了我们 VIDI RP 的可行性
(AI131385) 及其最后的礼物队列,该队列从 PWH 中收集死前和死后样本 (n=5)
或在死亡前未停止 ART (n=15)。 HOME 计划将允许该队列继续进行,同时
扩大科学范围,在单基因组和单细胞水平上研究人体中的艾滋病毒动态。
总之,整个 HOME 计划将深入描述控制艾滋病毒的环境因素
储库动力学,直接响应理解 HIV 储库动力学 RFA AI-21-013。
这一新知识将为艾滋病治疗策略提供信息,旨在逆转潜伏期(“休克和杀戮”)或沉默
永久深水库(“封锁和锁定”),并为减少当地艾滋病毒相关的方法提供新见解
组织损伤,这与炎症相关疾病有关。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Sara Gianella Weibel其他文献
Sara Gianella Weibel的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Sara Gianella Weibel', 18)}}的其他基金
Sex-differences in HIV persistence and Immune Dynamics during Reproductive Aging
生殖衰老过程中艾滋病毒持久性和免疫动态的性别差异
- 批准号:
10838316 - 财政年份:2023
- 资助金额:
$ 67.56万 - 项目类别:
Impact of Reproductive Aging On HIV Persistence and Inflammation
生殖衰老对艾滋病毒持续性和炎症的影响
- 批准号:
10433074 - 财政年份:2021
- 资助金额:
$ 67.56万 - 项目类别:
Mechanisms of CMV Replication on HIV Persistence
CMV 复制对 HIV 持续存在的机制
- 批准号:
10012877 - 财政年份:2020
- 资助金额:
$ 67.56万 - 项目类别:
The HIV-associated Opioid Micro-Environment (HOME) Project
HIV 相关阿片类药物微环境 (HOME) 项目
- 批准号:
10056153 - 财政年份:2020
- 资助金额:
$ 67.56万 - 项目类别:
Mechanisms of CMV Replication on HIV Persistence
CMV 复制对 HIV 持续存在的机制
- 批准号:
10241944 - 财政年份:2020
- 资助金额:
$ 67.56万 - 项目类别:
Mechanisms of CMV Replication on HIV Persistence
CMV 复制对 HIV 持续存在的机制
- 批准号:
10448351 - 财政年份:2020
- 资助金额:
$ 67.56万 - 项目类别:
Effect of Declining Sex Hormones on HIV persistence in HIV Infected Women on ART
性激素下降对接受 ART 的 HIV 感染妇女中 HIV 持续存在的影响
- 批准号:
9568360 - 财政年份:2017
- 资助金额:
$ 67.56万 - 项目类别:
Effect of Declining Sex Hormones on HIV persistence in HIV Infected Women on ART
性激素下降对接受 ART 的 HIV 感染妇女中 HIV 持续存在的影响
- 批准号:
9482258 - 财政年份:2017
- 资助金额:
$ 67.56万 - 项目类别:
相似海外基金
Practical Study on Disaster Countermeasure Architecture Model by Sustainable Design in Asian Flood Area
亚洲洪泛区可持续设计防灾建筑模型实践研究
- 批准号:
17K00727 - 财政年份:2017
- 资助金额:
$ 67.56万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Functional architecture of a face processing area in the common marmoset
普通狨猴面部处理区域的功能架构
- 批准号:
9764503 - 财政年份:2016
- 资助金额:
$ 67.56万 - 项目类别:
Heating and airconditioning by hypocausts in residential and representative architecture in Rome and Latium studies of a phenomenon of luxury in a favoured climatic area of the Roman Empire on the basis of selected examples.
罗马和拉齐奥的住宅和代表性建筑中的火烧供暖和空调根据选定的例子,研究了罗马帝国有利的气候地区的奢华现象。
- 批准号:
317469425 - 财政年份:2016
- 资助金额:
$ 67.56万 - 项目类别:
Research Grants
SBIR Phase II: Area and Energy Efficient Error Floor Free Low-Density Parity-Check Codes Decoder Architecture for Flash Based Storage
SBIR 第二阶段:用于基于闪存的存储的面积和能源效率高、无错误层的低密度奇偶校验码解码器架构
- 批准号:
1632562 - 财政年份:2016
- 资助金额:
$ 67.56万 - 项目类别:
Standard Grant
SBIR Phase I: Area and Energy Efficient Error Floor Free Low-Density Parity-Check Codes Decoder Architecture for Flash Based Storage
SBIR 第一阶段:用于基于闪存的存储的面积和能源效率高、无错误层低密度奇偶校验码解码器架构
- 批准号:
1520137 - 财政年份:2015
- 资助金额:
$ 67.56万 - 项目类别:
Standard Grant
A Study on The Spatial Setting and The Inhavitant's of The Flood Prevention Architecture in The Flood Area
洪泛区防洪建筑空间设置及居民生活研究
- 批准号:
26420620 - 财政年份:2014
- 资助金额:
$ 67.56万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Area and power efficient interconnect architecture for multi-bit processing on FPGAs
用于 FPGA 上多位处理的面积和功率高效互连架构
- 批准号:
327691-2007 - 财政年份:2011
- 资助金额:
$ 67.56万 - 项目类别:
Discovery Grants Program - Individual
A FUNDAMENTAL STUDY ON UTILIZATION OF THE POST-WAR ARCHITECTURE AS URBAN REGENERATION METHOD, A case of the central area of Osaka city
战后建筑作为城市更新方法的基础研究——以大阪市中心区为例
- 批准号:
22760469 - 财政年份:2010
- 资助金额:
$ 67.56万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Area and power efficient interconnect architecture for multi-bit processing on FPGAs
用于 FPGA 上多位处理的面积和功率高效互连架构
- 批准号:
327691-2007 - 财政年份:2010
- 资助金额:
$ 67.56万 - 项目类别:
Discovery Grants Program - Individual
Area and power efficient interconnect architecture for multi-bit processing on FPGAs
用于 FPGA 上多位处理的面积和功率高效互连架构
- 批准号:
327691-2007 - 财政年份:2009
- 资助金额:
$ 67.56万 - 项目类别:
Discovery Grants Program - Individual














{{item.name}}会员




