Deciphering brain mosaicism in drug-resistant epilepsy at cellular resolution
在细胞分辨率下解读耐药性癫痫中的大脑镶嵌现象
基本信息
- 批准号:10841995
- 负责人:
- 金额:$ 3.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2023-10-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdministrative SupplementAdultBehaviorBehavioralBrainCellsChildChildhoodChromatinCognitionCognitiveCommunicationDataDevelopmentEpigenetic ProcessEpilepsyExhibitsGenetic TranscriptionGoalsHippocampusIndividualIntellectual functioning disabilityIntractable EpilepsyKnowledgeLifeLinkLongitudinal StudiesMapsMentorshipMolecularMosaicismPharmaceutical PreparationsResearchResearch TrainingResolutionRiskSeizuresTechniquesTrainingbehavior testcareercell typeearly experienceepigenomicsinnovationlong-term sequelaemouse modelmultiple omicsnovel strategiesparent projectpre-doctoralprogramsresponseskillstranscriptomics
项目摘要
Project Summary
This administrative supplement will provide a predoctoral research training and mentorship program for Ms.
Sydney Townsend under the parent project R01NS129784 entitled “Deciphering brain mosaicism in drug-
resistant epilepsy at cellular resolution.” Ms. Townsend’s goal is to study the long-term consequences of pediatric
drug-resistant epilepsy, while developing her own analytical skills with a focus on single-cell transcriptomic and
epigenomic data. Early-life seizures, particularly those that are difficult to control with medication, have profound
consequences for brain development and function later in life. Up to half of children with epilepsy exhibit
intellectual disability and long-term deficits in communication, cognition, and behavior. Therefore, it is a critical
need to understand how early-life seizures alter brain development to develop treatment opportunities. Epilepsy
has been linked to transcriptional and epigenetic remodeling in the adult brain, but a major barrier to
understanding its developmental effects has been dissecting the acute vs. long-lasting contributions of individual
cell types. Understanding both acute and long-lasting molecular responses to early-life epilepsy on a cellular
level would inform the mechanisms through which long-term cognitive and behavioral deficits arise. This
application aims to bridge this gap in knowledge by using cutting-edge single-cell multiomics techniques to
investigate epigenetic and transcriptional changes in developing hippocampal cells following early-life seizures
using a mouse model. The second aim will map long-lasting molecular changes to hippocampal-dependent
behavioral consequences. The central hypothesis is that early-life seizures have long-lasting cell-type-specific
effects on transcription and chromatin accessibility that may account for the long-term cognitive and behavioral
effects. The rationale for this project is that understanding these changes will ultimately present new treatment
opportunities. The research proposed in this supplement application is highly innovative because it takes a new
approach to understanding the long-term sequalae of early-life seizures by leveraging leading-edge advances
in single-cell multiomics. The research aligns with the aims of the parent project by examining molecular and
functional effects of early-life epilepsy at cellular resolution, while addressing career training goals for Ms.
Townsend and promoting diversity in scientific research.
项目摘要
这一行政副刊将为MS提供博士前研究培训和指导计划。
西德尼·汤森德的母公司项目R01NS129784题为《破译毒品中的大脑马赛克--
在细胞分辨率下的难治性癫痫。汤森女士的目标是研究儿科治疗的长期后果
耐药癫痫,同时发展自己的分析技能,专注于单细胞转录和
表观基因组数据。早期癫痫,特别是那些很难用药物控制的癫痫,有着深远的影响
对晚年大脑发育和功能的影响。多达一半的癫痫儿童表现出
智力障碍和沟通、认知和行为的长期缺陷。因此,这是一个至关重要的问题
需要了解早期癫痫是如何改变大脑发育的,以开发治疗机会。癫痫
与成人大脑的转录和表观遗传重塑有关,但一个主要障碍是
对它的发展影响的理解一直在剖析个人的短期贡献和长期贡献
单元类型。在细胞上理解早期癫痫的急性和长期的分子反应
水平将为长期认知和行为缺陷的产生机制提供信息。这
应用程序旨在通过使用尖端的单细胞多组学技术来弥合这一知识差距
研究早期癫痫发作后发育中海马细胞的表观遗传学和转录变化
使用的是老鼠模型。第二个目标是将长期的分子变化映射到依赖于海马体
行为后果。中心假设是,早期癫痫发作具有持久的细胞类型特异性
对转录和染色质可及性的影响,这可能是长期认知和行为的原因
效果。这个项目的基本原理是,了解这些变化最终将提供新的治疗方法
机遇。这项补充申请中提出的研究具有很高的创新性,因为它采用了一种新的
利用前沿进展了解早期癫痫发作长期后遗症的方法
在单细胞多组学方面。这项研究与母项目的目标一致,通过检查分子和
早期癫痫在细胞分辨率上的功能影响,同时解决了MS的职业培训目标。
汤森和促进科学研究的多样性。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Tracy Ann Bedrosian其他文献
Tracy Ann Bedrosian的其他文献
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{{ truncateString('Tracy Ann Bedrosian', 18)}}的其他基金
Deciphering brain mosaicism in drug-resistant epilepsy at cellular resolution
在细胞分辨率下解读耐药性癫痫中的大脑镶嵌现象
- 批准号:
10563335 - 财政年份:2023
- 资助金额:
$ 3.34万 - 项目类别:
Mapping Somatic TE-derived Transcriptional Diversity
绘制体细胞 TE 衍生的转录多样性
- 批准号:
10155548 - 财政年份:2020
- 资助金额:
$ 3.34万 - 项目类别:
Mapping Somatic TE-derived Transcriptional Diversity
绘制体细胞 TE 衍生的转录多样性
- 批准号:
10386858 - 财政年份:2020
- 资助金额:
$ 3.34万 - 项目类别:
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