Computationally Driven Design of De Novo Genetically Encoded Voltage Indicators
De Novo 基因编码电压指示器的计算驱动设计
基本信息
- 批准号:9907495
- 负责人:
- 金额:$ 5万
- 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:2020-01-01 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:Action PotentialsAddressAdoptionAffectAffinityBehaviorBiliverdineBindingBinding ProteinsBiochemistryBrain DiseasesCellsCognitionComplexDirected Molecular EvolutionElectric CapacitanceElectrophysiology (science)EngineeringEscherichia coliExhibitsFilmFluorescenceFluorescence-Activated Cell SortingFrequenciesHippocampus (Brain)ImageIn VitroKineticsLigandsLipid BilayersLyaseMammalian CellMeasuresMembraneMembrane PotentialsMembrane Protein TrafficMental disordersMethodsModelingMonitorNeuronsOpticsPhenotypePhysiologyPositioning AttributePropertyProtein EngineeringProteinsProtocols documentationReporterReportingResistanceSamplingSideSignal TransductionSpectrum AnalysisStructureStudy modelsThinnessTissue imagingTissuesVariantViralWorkYeastsbasecell typechromophoredesigndichroismdipole momentelectric fieldexhaustionfluorescence imagingimprovedin vivoinsightnervous system disorderneuroimagingnovelpatch clampphycobilinreconstructionresponsesuccesstemporal measurementtraffickingvoltage
项目摘要
PROJECT SUMMARY:
Simultaneous optical monitoring of the electrical activity of hundreds of neurons with single-cell fidelity
comparable to whole-cell patch clamp electrophysiology would enable recording of the circuit-level activity that
gives rise to affect, behavior, and cognition and would drive novel insights into the network dysregulation
underlying psychiatric and neurological disorders. Therefore, enormous effort has been expended on designing
genetically encoded voltage indicators (GEVIs), cell-type specific protein reporters that transduce changes in
membrane potential as a fluorescent signal. Large-scale adoption of GEVIs is dependent on them possessing
the brightness, voltage-sensitivity, and temporal resolution to allow for the in vivo recording of high frequency
bursts, the monitoring of sub-threshold voltage dynamics, and the accurate reconstruction of action potential
waveforms. Current GEVIs, such as those constructed from archaerhodopsin, do not possess all these desired
properties and are intrinsically limited in their temporal resolution due to their reliance on structural
rearrangements for signal transduction. We propose the construction of high temporal resolution GEVIs by
leveraging validated methods in computational de novo protein design to produce transmembrane helical
bundle proteins that bind a near-infrared fluorescent, mammalian-endogenous biliverdin chromophore. Proper
positioning of biliverdin within the protein will allow for optical
voltage-reporting by the Stark effect, an
intrinsically voltage-sensitive phenomenon wherein an electric field acting upon a chromophore causes sub-
picosecond changes in fluorescence by altering absorbance. This work will produce near-infrared fluorescent,
high temporal resolution voltage probes permitting new insights into the circuit-level physiology underlying the
complex phenotypes seen in the normal and diseased brain.
项目概要:
以单细胞保真度同时光学监测数百个神经元的电活动
与全细胞膜片钳电生理学相比,
引起了情感、行为和认知,并将推动对网络失调的新见解
潜在的精神和神经疾病。因此,在设计上花费了巨大的努力,
基因编码的电压指示器(GEVI),细胞类型特异性蛋白质报告,
膜电位作为荧光信号。GEVI的大规模采用取决于它们拥有
亮度、电压灵敏度和时间分辨率,以允许在体内记录高频
爆发,监测阈下电压动态,并准确重建动作电位
波形目前的GEVI,例如由古视紫红质构建的GEVI,不具有所有这些期望的功能。
由于它们依赖于结构,
重排的信号转导。我们建议建设高时间分辨率GEVI的
利用经验证的计算从头蛋白质设计方法来产生跨膜螺旋
结合近红外荧光、哺乳动物内源性胆绿素发色团的束蛋白质。适当
胆绿素在蛋白质内的定位将允许光学
电压报告的斯塔克效应,
本征电压敏感现象,其中作用于发色团的电场引起亚-
通过改变吸光度使荧光发生皮秒变化。这项工作将产生近红外荧光,
高时间分辨率电压探头允许新的见解电路水平的生理基础
在正常和患病大脑中观察到的复杂表型。
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 }}
Ivan Kuznetsov其他文献
Ivan Kuznetsov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('Ivan Kuznetsov', 18)}}的其他基金
Computationally Driven Design of De Novo Genetically Encoded Voltage Indicators
De Novo 基因编码电压指示器的计算驱动设计
- 批准号:
10326360 - 财政年份:2020
- 资助金额:
$ 5万 - 项目类别:
Computationally Driven Design of De Novo Genetically Encoded Voltage Indicators
De Novo 基因编码电压指示器的计算驱动设计
- 批准号:
10556358 - 财政年份:2020
- 资助金额:
$ 5万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 5万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 5万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 5万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 5万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 5万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 5万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 5万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 5万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 5万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 5万 - 项目类别:
Research Grant