Precision pharmacology by local control of opioid receptors in neural circuits
通过局部控制神经回路中的阿片受体实现精准药理学
基本信息
- 批准号:10044383
- 负责人:
- 金额:$ 44.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-08-01 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:Absence of pain sensationAcuteAgonistAnalgesicsBehavioralBrainBreathingCytoplasmDangerousnessDevelopmentElectrophysiology (science)EnkephalinsG-Protein-Coupled ReceptorsGoalsHeroinHeterogeneityHyperalgesiaLocationMediatingMembraneMethodsModelingMolecularMorphineMusNeuronsNeuropeptidesNociceptionOpiate AddictionOpioidOpioid PeptideOpioid ReceptorPathologicPeptidesPharmaceutical PreparationsPharmacologyPharmacotherapyPhasePhysiologicalPreparationProteinsPsychological reinforcementReceptor ActivationReceptor SignalingRecombinant adeno-associated virus (rAAV)ResolutionSeriesSignal TransductionSliceSpinal CordSystemTechnologyTestingTherapeuticTherapeutic IndexTimeTissuesVentilatory Depressionbasebehavioral responseclinically relevantcomparative efficacydrug actionefficacy testingendogenous opioidshigh riskimprovedin vivoinsightinstrumentmu opioid receptorsnanobodiesneural circuitneuroregulationnoveloptogeneticsprogramsreceptorreceptor functionrecruitside effecttool
项目摘要
PROJECT SUMMARY
This proposal seeks to leverage the emerging understanding of cellular and subcellular heterogeneity in opioid
signaling for therapeutic discovery. The project develops new optogenetic and chemogenetic tools to achieve
local control of opioid receptor activity and signaling in neural circuits and at a subcellular level of resolution. The
proposal seeks to develop a versatile toolbox and provide proof-of-concept for "in vivo precision pharmacology"
that have not yet been applied to the opioid system. The first phase (R61) is a "high-risk" technology enabling
phase, based on combining our collaborative team's expertise in developing receptor-blocking intracellular
nanobodies with established methods for conferring local control of nanobody concentration in the cytoplasm
and specific membrane domains, using optogenetic and chemogenetic strategies that have already been
validated but never before applied to opioid receptors. The R61 phase will develop these tools (Specific Aim 1)
and validate them in neuronal culture and acute slice preparations (Specific Aim 2). These studies will provide
not only proof-of-concept for in vivo precision pharmacology of opioid receptors, but also for G protein-coupled
receptors as a class. We have set a specific series of milestones to evaluate progress, and to assess feasibility
for advance to in vivo studies. If the milestones are successfully met, the second phase (R33) will apply the new
tools to selectively target opioid signaling in neural circuits in vivo, focusing on analgesia, behavioral
reinforcement and respiratory depression by clinically relevant opioid drugs. Mice are used as a well-established
and relevant model (Specific Aim 3). These studies leverage the combined expertise of our collaborative team,
and will establish powerful optogenetic and chemogenetic manipulations for the study of in vivo opioid function
for the first time. Accordingly, the proposed studies to provide the first-in-class application of optogenetic and
chemogenetic control to the opioid system in vivo, and they will explore a precision pharmacology of opioids
based on location in neural circuits.
项目总结
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 }}
Aashish Manglik其他文献
Aashish Manglik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('Aashish Manglik', 18)}}的其他基金
Mechanisms of Smoothened Activation in Hedgehog Signaling
Hedgehog 信号传导平滑激活机制
- 批准号:
10365068 - 财政年份:2022
- 资助金额:
$ 44.33万 - 项目类别:
Mechanisms of Smoothened Activation in Hedgehog Signaling
Hedgehog 信号传导平滑激活机制
- 批准号:
10552682 - 财政年份:2022
- 资助金额:
$ 44.33万 - 项目类别:
Enhancing olfactory receptor expression for biochemical studies of odorant-receptor interactions
增强嗅觉受体表达以进行气味受体相互作用的生化研究
- 批准号:
10580041 - 财政年份:2022
- 资助金额:
$ 44.33万 - 项目类别:
Enhancing olfactory receptor expression for biochemical studies of odorant-receptor interactions
增强嗅觉受体表达以进行气味受体相互作用的生化研究
- 批准号:
10465009 - 财政年份:2022
- 资助金额:
$ 44.33万 - 项目类别:
Precision pharmacology by local control of opioid receptors in neural circuits
通过局部控制神经回路中的阿片受体实现精准药理学
- 批准号:
10219227 - 财政年份:2020
- 资助金额:
$ 44.33万 - 项目类别:
Precision pharmacology by local control of opioid receptors in neural circuits
通过局部控制神经回路中的阿片受体实现精准药理学
- 批准号:
10405103 - 财政年份:2020
- 资助金额:
$ 44.33万 - 项目类别:
Biochemical approaches to enlighten GPR85 function
生化方法揭示 GPR85 功能
- 批准号:
10047548 - 财政年份:2020
- 资助金额:
$ 44.33万 - 项目类别:
相似海外基金
Elucidation of acute poisoning mechanism due to abuse of CB1 receptor agonist.
阐明滥用 CB1 受体激动剂引起的急性中毒机制。
- 批准号:
21K17323 - 财政年份:2021
- 资助金额:
$ 44.33万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of acute poisoning mechanism due to abuse of CB1 receptor agonist.
阐明滥用 CB1 受体激动剂引起的急性中毒机制。
- 批准号:
19K19485 - 财政年份:2019
- 资助金额:
$ 44.33万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Tissue repair effect in acute myocardial infarction through mobilization of endogenous Muse cells by sphingosine-1-phosphate receptor 2 agonist
1-磷酸鞘氨醇受体2激动剂动员内源性Muse细胞对急性心肌梗死的组织修复作用
- 批准号:
18K15843 - 财政年份:2018
- 资助金额:
$ 44.33万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6115624 - 财政年份:1998
- 资助金额:
$ 44.33万 - 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6219539 - 财政年份:1998
- 资助金额:
$ 44.33万 - 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6276858 - 财政年份:1997
- 资助金额:
$ 44.33万 - 项目类别:
ACUTE CHRONIC HORMONAL CHANGES WITH LHRH-AGONIST THERAPY
LHRH 激动剂治疗引起的急性慢性荷尔蒙变化
- 批准号:
6250152 - 财政年份:1997
- 资助金额:
$ 44.33万 - 项目类别:
ACUTE CHRONIC HORMONAL CHANGES WITH LHRH-AGONIST THERAPY
LHRH 激动剂治疗引起的急性慢性荷尔蒙变化
- 批准号:
6279945 - 财政年份:1997
- 资助金额:
$ 44.33万 - 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6246787 - 财政年份:1997
- 资助金额:
$ 44.33万 - 项目类别:
PSYCHOPHARMACOLOGY OF DA AGONIST CNS EFFECTS: ACUTE AND CHRONIC STUDIES
DA 激动剂中枢神经系统影响的精神药理学:急性和慢性研究
- 批准号:
3891471 - 财政年份:
- 资助金额:
$ 44.33万 - 项目类别: