Combining new molecular and informatic strategies to find hidden ways to treat brain disease
结合新的分子和信息学策略来寻找治疗脑部疾病的隐藏方法
基本信息
- 批准号:10307079
- 负责人:
- 金额:$ 112.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-12-01 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAstrocytesBasic ScienceBig DataBiological ModelsBrainBrain DiseasesCellsComputational ScienceDNAData AnalysesDefectDiseaseEtiologyGeneticGoalsHealthHumanIndividualInformaticsKnowledgeMediatingMethodsMicrogliaModernizationMolecularMolecular BiologyNeurologistNeuronsNeurosciencesPatientsPlant RootsProtein IsoformsProteinsRNARegulationScienceTechnologycell typedruggable targetnervous system disordernew technologyreceptorstoichiometrysuccesstargeted treatmenttherapeutic target
项目摘要
The key challenge addressed in this proposal is to develop a means to harness the power of molecular biology to define therapeutic targets for brain disease. This treatment-oriented approach combines the urgency of a practicing neurologist with the knowledge and technology modern science brings to neuroscience. From the basic science perspective, understanding the fundamental root mechanism of disease is an uncompromising goal. From the neurologist's perspective, the perfect cannot be the enemy of the good, leading to five basic points: · Success to date in the treatment of brain disease offers a key lesson in focus. Treatments target accessible molecules, and this will dictate how we focus big data analysis. · Human neurologic disease is complicated. The best model system for understanding neurologic disorders is the human; studies of human brain material must be integral to developing new treatments. · Regardless of the cause of brain disease—and current neuroscience is appropriately focused on tracing “genetic” (DNA) etiologies—the manifestations of such defects are mediated by the stoichiometry, distribution and variability of cell-specific RNA regulation and its consequent effects on proteins within affected cells. · Different cell types contribute to different brain disorders, but the difference between individual cells of any one type is unknown. The differences between them are manifest at the level of RNA, not DNA. · The quantity, quality (isoforms) and distribution of targets (e.g., receptors) are enormous. The unique spectrum of diversity of an individual cell type—neurons, astrocytes or microglial cells—is unknown, more so when comparing diseased and normal brain. Using a variety of new strategies, we will study RNA regulation in individual cell types. · Bridging these points together requires new methods and computational approaches. · The net result of contrasting RNA regulation in individual human cell types in health and disease will uncover otherwise hidden cell type-specific targets for therapeutics.
本提案提出的关键挑战是开发一种方法来利用分子生物学的力量来确定脑部疾病的治疗靶点。这种以治疗为导向的方法结合了执业神经科医生的紧迫性和现代科学给神经科学带来的知识和技术。从基础科学的角度来看,了解疾病的根本机制是一个不可妥协的目标。从神经学家的角度来看,完美不可能是好的敌人,这就引出了五个基本要点:·迄今为止,治疗脑部疾病的成功提供了一个关键的教训,那就是专注。治疗的目标是可获得的分子,这将决定我们如何关注大数据分析。·人类神经系统疾病很复杂。理解神经系统疾病的最佳模型系统是人类;对人类大脑物质的研究必须是开发新疗法不可或缺的一部分。·不管脑病的病因是什么——目前的神经科学正适当地关注于追踪“遗传”(DNA)病因——这些缺陷的表现是由细胞特异性RNA调控的化学计量、分布和变异性及其对受影响细胞内蛋白质的后续影响所介导的。·不同的细胞类型导致不同的脑部疾病,但任何一种类型的单个细胞之间的差异是未知的。它们之间的差异体现在RNA水平上,而不是DNA水平上。·靶标(如受体)的数量、质量(同种异构体)和分布是巨大的。单个细胞类型(神经元、星形胶质细胞或小胶质细胞)的独特多样性谱是未知的,在比较患病和正常大脑时更是如此。使用各种新的策略,我们将研究单个细胞类型中的RNA调控。·将这些点连接在一起需要新的方法和计算方法。·对比健康和疾病中个体人类细胞类型的RNA调控的最终结果将揭示治疗中隐藏的细胞类型特异性靶点。
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 }}
ROBERT B DARNELL其他文献
ROBERT B DARNELL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('ROBERT B DARNELL', 18)}}的其他基金
Combining New Molecular and Informatic Strategies to Find Hidden Ways to Treat Brain Disease
结合新的分子和信息策略来寻找治疗脑疾病的隐藏方法
- 批准号:
10528460 - 财政年份:2016
- 资助金额:
$ 112.76万 - 项目类别:
Combining new molecular and informatic strategies to find hidden ways to treat brain disease
结合新的分子和信息学策略来寻找治疗脑部疾病的隐藏方法
- 批准号:
9161392 - 财政年份:2016
- 资助金额:
$ 112.76万 - 项目类别:
New York Center for Collaborative Research in Common Disease Genomics
纽约常见疾病基因组学合作研究中心
- 批准号:
9050000 - 财政年份:2016
- 资助金额:
$ 112.76万 - 项目类别:
Combining new molecular and informatic strategies to find hidden ways to treat brain disease
结合新的分子和信息学策略来寻找治疗脑部疾病的隐藏方法
- 批准号:
10056984 - 财政年份:2016
- 资助金额:
$ 112.76万 - 项目类别:
Mapping the mechanisms of protein synthesis-dependent synaptic plasticity
绘制蛋白质合成依赖性突触可塑性的机制
- 批准号:
8703829 - 财政年份:2012
- 资助金额:
$ 112.76万 - 项目类别:
Mapping the mechanisms of protein synthesis-dependent synaptic plasticity
绘制蛋白质合成依赖性突触可塑性的机制
- 批准号:
9113688 - 财政年份:2012
- 资助金额:
$ 112.76万 - 项目类别:
Mapping the mechanisms of protein synthesis-dependent synaptic plasticity
绘制蛋白质合成依赖性突触可塑性的机制
- 批准号:
8898256 - 财政年份:2012
- 资助金额:
$ 112.76万 - 项目类别:
Mapping the mechanisms of protein synthesis-dependent synaptic plasticity
绘制蛋白质合成依赖性突触可塑性的机制
- 批准号:
8412332 - 财政年份:2012
- 资助金额:
$ 112.76万 - 项目类别:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 112.76万 - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 112.76万 - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 112.76万 - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 112.76万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 112.76万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 112.76万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 112.76万 - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
$ 112.76万 - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 112.76万 - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
$ 112.76万 - 项目类别:
Grant-in-Aid for Early-Career Scientists