Epigenetic regulation of the circadian gene Per1 in age-related memory impairments
Epigenetic regulation of the circadian gene Per1 in age-related memory impairments
批准号:
10171743
负责人:
JANINE LYNN KWAPIS
金额:
$24.9万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-09-01 至 2023-05-31
关键词:
AffectAgeAge-associated memory impairmentAgingAlzheimer&aposs DiseaseAmericanAnimalsCREBBP geneCaliforniaChromatin StructureCircadian DysregulationCircadian RhythmsClustered Regularly Interspaced Short Palindromic RepeatsCollaborationsDataDeacetylaseDevelopmentDevelopment PlansDiseaseDorsalEngineeringEnvironmentEpigenetic ProcessFoundationsFunctional disorderFundingFutureGene ExpressionGene Expression RegulationGenesGeneticGenetic EngineeringGenetic TranscriptionGoalsGrantHDAC3 geneHippocampus (Brain)Histone AcetylationImpaired cognitionImpairmentIndividualInstitutionInterventionJob ApplicationLaboratoriesLeadLearningLinkMediatingMemoryMemory impairmentMolecularMolecular BiologyMusPeriodicityPlayPopulationPositioning AttributeProcessRegulationRepressionResearchResearch PersonnelRoleScientistSiteSmall Interfering RNATechnical ExpertiseTechnologyTestingTimeTrainingUniversitiesVirusWritingage relatedaging brainaging hippocampusbasecareerchromatin immunoprecipitationchromatin remodelingcircadiancircadian pacemakercircadian regulationcognitive functiondesignepigenetic regulationexperienceexperimental studygene repressionhistone acetyltransferasehistone modificationjuvenile animalknock-downlong term memorymemory consolidationmild cognitive impairmentmutantneuromechanismnormal agingnovelnovel therapeuticsoverexpressionpreventprogramspromoterprotein protein interactionremediationskillstranscriptome sequencingtreatment strategy
中文摘要
项目摘要/摘要
阿尔茨海默病影响着540万美国人[1],到2030年,大约有1380万人65岁或以上
老年人预计会患上这种疾病[2]。更多的人将经历正常的与年龄相关的认知
衰退、轻度认知障碍和长期记忆形成障碍。因此,至关重要的是
在正常年龄依赖的认知背景下理解记忆形成的潜在机制
拒绝。这项提议测试了PER1是否是将异常的表观遗传联系起来的关键的新机制
具有昼夜节律性和年龄相关性损害的老化脑中转录抑制
长期记忆的形成。首先,这项提议将测试组蛋白脱乙酰酶的抑制活性
3(HDAC3)导致与年龄相关的记忆形成和基因表达障碍。接下来,它将
确定PER1是否是HDAC3限制老化大脑中记忆形成的机制。
最后,使用基于CRISPR/dCas9的基因工程方法,该项目将测试特定部位
PER1的表观遗传操作可以改善记忆形成中与年龄相关的损伤。团结在一起,
这项提议中的实验将确定昼夜节律基因PER1的表观遗传失调是否在
在长期记忆形成中,背侧海马区与年龄相关的损害有关。
拟议的项目还将帮助候选人Janine Kuapis博士实现她的职业目标,成为
一家专注于研究的机构的独立调查员。该项目提供尖端技术方面的培训
研究技能,包括CRISPR/dCas9技术的开发和应用以及
昼夜节律研究。此外,拟议的研究将为一项研究计划奠定基础
远远超出了拟议的拨款范围。加州大学欧文分校为
与世界知名的记忆、衰老、昼夜节律方面的专家一起培训候选人这些新的技术技能
节律和分子生物学。此外,UCI提供了一个智力环境,鼓励
协作与合作,使候选人能够成长为一名科学家,并为成功的
职业生涯。除了拟议的研究外,夸皮斯博士还将参与一系列旨在
为她成功地实现独立做好准备,包括培训勇气、演讲、
科学写作、教学培训、求职申请和实验室管理。在这里提出的系统计划
(包括研究计划和候选人发展计划)被校准以产生一个成功的、
执行可支持新实验室的独特尖端研究的独立研究科学家
并处于有利地位,可以获得未来的R01资金。
英文摘要
Project Summary/Abstract
Alzheimer's Disease affects 5.4 million Americans [1] and by 2030, approximately 13.8 million people 65 or
older are projected to have the disease [2]. Even more individuals will experience normal age-related cognitive
decline, mild cognitive impairment, and impairments in long-term memory formation. It is therefore critical to
understand the mechanisms underlying memory formation in the context of normal age-dependent cognitive
decline. This proposal tests whether Per1 is a key novel mechanism that links aberrant epigenetic
transcriptional repression in the aging brain with age-related impairments in both circadian rhythmicity and
long-term memory formation. First, this proposal will test whether the repressive activity of histone deacetylase
3 (HDAC3) contributes to age-related impairments in both memory formation and gene expression. Next, it will
determine whether Per1 is a mechanism through which HDAC3 limits memory formation in the aging brain.
Finally, using a CRISPR/dCas9-based genetic engineering approach, this project will test whether site-specific
epigenetic manipulations at Per1 can ameliorate age-related impairments in memory formation. Together, the
experiments in this proposal will determine whether epigenetic dysregulation of the circadian gene Per1 in the
dorsal hippocampus contributes to age-related impairments in long-term memory formation.
The proposed project will also help the candidate, Dr. Janine Kwapis, achieve her career goal of becoming
an independent investigator at a research-focused institution. This project provides training in cutting-edge
research skills, including the development and application of CRISPR/dCas9 technology and training in
circadian rhythm research. Further, the proposed studies will lay the foundation for a research program that
extends well beyond the proposed grant. The University of California, Irvine provides an ideal environment for
training the candidate in these new technical skills, with world-renowned experts in memory, aging, circadian
rhythms, and molecular biology. Further, UCI provides an intellectual environment that encourages
collaboration and cooperation, allowing the candidate to grow as a scientist and prepare for a successful
career. In addition to the proposed research, Dr. Kwapis will engage in a number of activities designed to
prepare her to successfully achieve independence, including training in grantsmanship, presentations,
scientific writing, didactic training, job application, and lab management. The systematic plan proposed here
(including both the research plan and the candidate development plan) is calibrated to produce a successful,
independent research scientist who performs unique cutting-edge research that can support a new laboratory
and is well-positioned to receive future R01 funding.
期刊论文(4)
专著(0)
科研奖励(0)
会议论文
Time to learn: The role of the molecular circadian clock in learning and memory.
学习时间:分子昼夜节律在学习和记忆中的作用。
DOI:
10.1016/j.nlm.2022.107651
发表时间:
2022-09
期刊:
NEUROBIOLOGY OF LEARNING AND MEMORY
影响因子:
2.7
作者:
[Smies, Chad W., Bodinayake, Kasuni K., Kwapis, Janine L.]
通讯作者:
Kwapis, Janine L.
DOI:
10.1016/j.neubiorev.2019.12.013
发表时间:
2020-01
期刊:
Neuroscience and biobehavioral reviews
影响因子:
8.2
作者:
[Navabpour S, Kwapis JL, Jarome TJ]
通讯作者:
Jarome TJ
DOI:
10.1016/j.nlm.2021.107535
发表时间:
2021-11
期刊:
Neurobiology of learning and memory
影响因子:
2.7
作者:
[Urban MW, Lo C, Bodinayake KK, Brunswick CA, Murakami S, Heimann AC, Kwapis JL]
通讯作者:
Kwapis JL
Diurnal control of memory allocation by the circadian gene Per1
-
批准号:10683292
-
项目类别:
-
资助金额:$30.28万
-
财政年份:2022
-
负责人:JANINE LYNN KWAPIS
-
依托单位:
Diurnal control of memory allocation by the circadian gene Per1
-
批准号:10515899
-
项目类别:
-
资助金额:$31.01万
-
财政年份:2022
-
负责人:JANINE LYNN KWAPIS
-
依托单位:
The role of HDAC3 in age-related impairments in memory updating
-
批准号:10039300
-
项目类别:
-
资助金额:$42.97万
-
财政年份:2020
-
负责人:JANINE LYNN KWAPIS
-
依托单位:
Epigenetic regulation of the circadian gene Per1 in age-related memory impairments
-
批准号:10002164
-
项目类别:
-
资助金额:$24.9万
-
财政年份:2019
-
负责人:JANINE LYNN KWAPIS
-
依托单位:
Epigenetic repression of synaptic plasticity and memory in the aging brain
-
批准号:9198722
-
项目类别:
-
资助金额:$3.4万
-
财政年份:2016
-
负责人:JANINE LYNN KWAPIS
-
依托单位:
The role of protein kinase Mzeta in hippocampal-dependent memory maintenance.
-
批准号:8209722
-
项目类别:
-
资助金额:$4.22万
-
财政年份:2011
-
负责人:JANINE LYNN KWAPIS
-
依托单位:
The role of protein kinase Mzeta in hippocampal-dependent memory maintenance.
-
批准号:8059965
-
项目类别:
-
资助金额:$4.11万
-
财政年份:2011
-
负责人:JANINE LYNN KWAPIS
-
依托单位:
The role of protein kinase Mzeta in hippocampal-dependent memory maintenance.
-
批准号:8399106
-
项目类别:
-
资助金额:$4.22万
-
财政年份:2011
-
负责人:JANINE LYNN KWAPIS
-
依托单位:
国内基金
海外基金
登录
查看更多内容
补阳还五汤通过AGE-RAGE通路调控脓毒症免疫失衡的机制与转化研究
-
批准号:JCZRLH202601523
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:
-
依托单位:
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
-
批准号:JCZRQN202500010
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2025
-
负责人:
-
依托单位:
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
-
批准号:2025JJ70209
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2025
-
负责人:雷芬芳
-
依托单位:
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
-
批准号:--
-
项目类别:面上项目
-
资助金额:--
-
批准年份:2024
-
负责人:万荣
-
依托单位:
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
-
批准号:2023JJ50274
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2023
-
负责人:贺志明
-
依托单位:
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
-
批准号:--
-
项目类别:地区科学基金项目
-
资助金额:33万元
-
批准年份:2022
-
负责人:都义日
-
依托单位:
补肾健脾祛瘀方调控AGE/RAGE信号通路在再生障碍性贫血骨髓间充质干细胞功能受损的作用与机制研究
-
批准号:--
-
项目类别:面上项目
-
资助金额:52万元
-
批准年份:2022
-
负责人:叶宝东
-
依托单位:
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
-
批准号:
-
项目类别:省市级项目
-
资助金额:10.0万元
-
批准年份:2022
-
负责人:于海兵
-
依托单位:
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
-
批准号:81973577
-
项目类别:面上项目
-
资助金额:55.0万元
-
批准年份:2019
-
负责人:辛贵忠
-
依托单位:
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
-
批准号:81602908
-
项目类别:青年科学基金项目
-
资助金额:18.0万元
-
批准年份:2016
-
负责人:刘括
-
依托单位: