Design of Fe2+ and H2O2 Induced Proximity Functionalized Imaging Probes for the Control of Cellular Functions
用于控制细胞功能的 Fe2 和 H2O2 诱导接近功能化成像探针的设计
基本信息
- 批准号:10388365
- 负责人:
- 金额:$ 28.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-05-01 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:Abscisic AcidAddressBiologicalBiological ProcessBiomedical ResearchBiotechnologyBrain-Derived Neurotrophic FactorBuffersCell DeathCell TherapyCell physiologyCellsChemicalsComplexCuesDetectionDiseaseEngineeringEnvironmentEventFluorescence MicroscopyFunctional ImagingFutureGenesGeneticGibberellinsHigh Pressure Liquid ChromatographyHydrogen PeroxideImmune responseKnowledgeLogicLuciferasesMediatingMediator of activation proteinMethodsMicroscopyMolecular BiologyMutationNatureNeurodegenerative DisordersNeuronsNoiseOxidative StressPathway interactionsProductionProteinsReportingResearchResearch ProposalsSeriesSignal PathwaySignal TransductionSignaling MoleculeSiteSpecificityStimulusTechnologyTestingTherapeuticToxic effectTranslationsbiological systemsdesigngene therapyimaging probeimprovedinnovationnew technologynovelplasmid DNAprogramsprotective effectsensorside effectspatiotemporalstability testingsynthetic biologytheranosticstherapeutic proteintool
项目摘要
Project Summary
Gene/cell therapies finally come of age thanks to the fundamental advances made by innovative and
improved biotechnologies. Nonetheless, many challenges particularly toxicity and undesired/uncontrolled
immune response remain. This research proposal addresses these concerns and represents a critical first step
toward developing novel, more effective cell/gene therapy. Toward this end, we propose a novel synthetic
biology technology termed “Environment Stimuli-Induced Proximity (ESIP)” to spatiotemporally manipulate
cellular functions. The new strategy can overcome the difficulty of the established chemically induced proximity
(CIP) method to mediate the translation of endogenous cellular signals into tailored cellular functions with
spatiotemporal precision. To demonstrate the feasibility, we propose to develop fluorescent and
chemiluminescent Fe(II) and H2O2 responsive ESIP chemical inducers because Fe(II) and H2O2 are important
signal molecules, which are associated with numerous biological functions and diseases, and gibberellin (GA)
and abscisic acid (ABA) are established chemical inducers with low toxicity. Specifically, we will design,
synthesize, test and optimize Fe2+ and H2O2-responsive fluorescent and chemiluminescent ESIP inducers
(Specific Aims 1-2) and test them in cells and construct ESIP-mediated “AND” Boolean logic gates to control the
conditional production of AD therapeutic proteins (Specific Aim 3). These studies will prove that these `smart'
theranostic probes possess the ability to sense endogenous Fe(II) and H2O2 specifically, and the ability to trigger
the release of original bioactive chemical inducers GA and ABA, which then induce downstream biological
functions such as luciferase expression and the production of neuron protective BDNF proteins. The technology
will ultimately be transformed into entirely new cell/gene therapies for disease treatment with significantly
reduced side effects. It is expected that this powerful and general strategy can be integrated with a variety of
existing synthetic biology molecular parts and tools to build new cellular genetic and signaling circuitries to
generate new functions as toolbox for biomedical research and as therapeutics for various disease treatment.
项目摘要
基因/细胞疗法终于成熟了,这要归功于创新和
改进的生物技术。尽管如此,许多挑战,特别是毒性和不希望的/不受控制的
免疫反应仍然存在。这项研究提案解决了这些问题,是关键的第一步。
开发新的、更有效的细胞/基因疗法。为此,我们提出了一种新的合成
被称为“环境刺激诱导邻近(ESIP)”的生物技术来时空操纵
细胞功能。新策略可以克服已建立的化学诱导邻近的困难
(CIP)介导内源性细胞信号翻译成定制细胞功能的方法,
时空精度为了证明可行性,我们建议开发荧光和
荧光Fe(II)和H2 O2响应的ESIP化学诱导剂,因为Fe(II)和H2 O2是重要的
与多种生物学功能和疾病相关的信号分子,以及赤霉素(GA)
和脱落酸(阿坝)是公认的低毒化学诱导剂。具体来说,我们将设计,
Fe ~(2+)和H_2O_2响应性荧光和荧光ESIP诱导剂合成、测试和优化
(具体目的1-2)并在细胞中测试它们,并构建ESIP介导的“与”布尔逻辑门以控制细胞的增殖。
AD治疗性蛋白质的条件性产生(特异性目标3)。这些研究将证明,这些“聪明”的
治疗诊断探针具有特异性地感测内源性Fe(II)和H2 O2的能力,以及触发
原始生物活性化学诱导物GA和阿坝的释放,其然后诱导下游生物活性物质的释放,
功能如荧光素酶表达和神经元保护性BDNF蛋白的产生。技术
最终将转化为全新的细胞/基因疗法,用于疾病治疗,
减少副作用。预计这一强有力的通用战略可以与各种
现有的合成生物学分子部件和工具,以建立新的细胞遗传和信号电路,
作为生物医学研究的工具箱和各种疾病治疗的治疗剂产生新的功能。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Senolysis Enabled by Senescent Cell-Sensitive Bioorthogonal Tetrazine Ligation.
通过衰老细胞敏感的生物正交四嗪连接实现衰老分解。
- DOI:10.1002/anie.202315425
- 发表时间:2024
- 期刊:
- 影响因子:0
- 作者:Chang,Mengyang;Dong,Yue;Xu,Hang;Cruickshank-Taylor,AlexisB;Kozora,JacobS;Behpour,Baran;Wang,Wei
- 通讯作者:Wang,Wei
A theranostic abscisic acid-based molecular glue.
- DOI:10.1039/d2sc06995d
- 发表时间:2023-03-22
- 期刊:
- 影响因子:8.4
- 作者:
- 通讯作者:
Building bioorthogonal click-release capable artificial receptors on cancer cell surface for imaging, drug targeting and delivery.
- DOI:10.1016/j.apsb.2022.12.018
- 发表时间:2023-06
- 期刊:
- 影响因子:14.5
- 作者:Chen, Jing;Ji, Peng;Gnawali, Giri;Chang, Mengyang;Gao, Feng;Xu, Hang;Wang, Wei
- 通讯作者:Wang, Wei
MDM2-BCL-XL PROTACs enable degradation of BCL-XL and stabilization of p53.
- DOI:10.15212/amm-2022-0022
- 发表时间:2022-07-21
- 期刊:
- 影响因子:0
- 作者:Chang, Mengyang;Gao, Feng;Wang, Wei
- 通讯作者:Wang, Wei
{{
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 }}
WEI WANG其他文献
Pricing and hedging catastrophe equity put options under a Markov-modulated jump diffusion model
马尔可夫调制跳跃扩散模型下的巨灾股票看跌期权的定价和对冲
- DOI:
10.3934/jimo.2015.11.493 - 发表时间:
2014-09 - 期刊:
- 影响因子:1.3
- 作者:
WEI WANG;LINYI QIAN;XIAONAN SU - 通讯作者:
XIAONAN SU
WEI WANG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('WEI WANG', 18)}}的其他基金
Design of Fe2+ and H2O2 Induced Proximity Functionalized Imaging Probes for the Control of Cellular Functions
用于控制细胞功能的 Fe2 和 H2O2 诱导接近功能化成像探针的设计
- 批准号:
9918434 - 财政年份:2019
- 资助金额:
$ 28.72万 - 项目类别:
Organocatalytic Practical Synthesis of Deuterated Building Blocks and Biologically Important Structures
氘代结构单元和生物学重要结构的有机催化实际合成
- 批准号:
9892834 - 财政年份:2018
- 资助金额:
$ 28.72万 - 项目类别:
Organocatalytic Practical Synthesis of Deuterated Building Blocks and Biologically Important Structures
氘代结构单元和生物学重要结构的有机催化实际合成
- 批准号:
9918424 - 财政年份:2018
- 资助金额:
$ 28.72万 - 项目类别:
Organocatalytic Practical Synthesis of Deuterated Building Blocks and Biologically Important Structures
氘代结构单元和生物学重要结构的有机催化实际合成
- 批准号:
10115754 - 财政年份:2018
- 资助金额:
$ 28.72万 - 项目类别:
BINDING SPECIFICITY OF PEPTIDE RECOGNITION DOMAINS
肽识别域的结合特异性
- 批准号:
7367782 - 财政年份:2006
- 资助金额:
$ 28.72万 - 项目类别:
A SYSTEMATIC APPROACH TO RECONSTRUCTING TRANSCRIPTION NETWORKS IN THE CELL
重建细胞转录网络的系统方法
- 批准号:
7180239 - 财政年份:2005
- 资助金额:
$ 28.72万 - 项目类别:
Enhanced cardiac sympathetic afferent reflex in CHF
CHF 患者心脏交感神经传入反射增强
- 批准号:
6815913 - 财政年份:2004
- 资助金额:
$ 28.72万 - 项目类别:
A SYSTEMATIC APPROACH TO RECONSTRUCTING TRANSCRIPTION
重建转录的系统方法
- 批准号:
6976119 - 财政年份:2004
- 资助金额:
$ 28.72万 - 项目类别:
相似海外基金
Systems modeling to address the social and biological drivers of disparities in infection and mortality from emerging infectious diseases
用于解决新发传染病感染和死亡率差异的社会和生物驱动因素的系统建模
- 批准号:
10669177 - 财政年份:2022
- 资助金额:
$ 28.72万 - 项目类别:
Systems modeling to address the social and biological drivers of disparities in infection and mortality from emerging infectious diseases
用于解决新发传染病感染和死亡率差异的社会和生物驱动因素的系统建模
- 批准号:
10415713 - 财政年份:2022
- 资助金额:
$ 28.72万 - 项目类别:
Transporting established insights from classical experimental design to address causal questions in environmental epidemiology including the understanding of biological mediating mechanisms
运用经典实验设计的既定见解来解决环境流行病学中的因果问题,包括对生物介导机制的理解
- 批准号:
10395286 - 财政年份:2021
- 资助金额:
$ 28.72万 - 项目类别:
Advancing cryo-EM technology to address difficult biological questions
推进冷冻电镜技术解决棘手的生物学问题
- 批准号:
10570241 - 财政年份:2021
- 资助金额:
$ 28.72万 - 项目类别:
Advancing cryo-EM technology to address difficult biological questions
推进冷冻电镜技术解决棘手的生物学问题
- 批准号:
10166355 - 财政年份:2021
- 资助金额:
$ 28.72万 - 项目类别:
Advancing cryo-EM technology to address difficult biological questions
推进冷冻电镜技术解决棘手的生物学问题
- 批准号:
10376252 - 财政年份:2021
- 资助金额:
$ 28.72万 - 项目类别:
Building Infrastructure to Address Social, Cultural and Biological Determinants of Diabetes in Lebanon
建设基础设施以解决黎巴嫩糖尿病的社会、文化和生物决定因素
- 批准号:
10237378 - 财政年份:2020
- 资助金额:
$ 28.72万 - 项目类别:
Reprogramming genetic information at the RNA level: optimizing tools to address specific biological questions
在 RNA 水平上重新编程遗传信息:优化工具来解决特定的生物学问题
- 批准号:
404867268 - 财政年份:2018
- 资助金额:
$ 28.72万 - 项目类别:
Priority Programmes
Biological soil crusts as unique microecosystem represent a suitable model system to address taxonomy and cryptic diversity of microalgal key players
生物土壤结皮作为独特的微生态系统,代表了解决微藻关键参与者的分类学和神秘多样性的合适模型系统
- 批准号:
350173788 - 财政年份:2017
- 资助金额:
$ 28.72万 - 项目类别:
Priority Programmes
Multidisciplinary translational research to address social disparities in osteoporosis: Understanding the social context of biological mechanisms
解决骨质疏松症社会差异的多学科转化研究:了解生物机制的社会背景
- 批准号:
nhmrc : 1107510 - 财政年份:2016
- 资助金额:
$ 28.72万 - 项目类别:
Career Development Fellowships