Microtubule dynamics and error correction
微管动力学和误差校正
基本信息
- 批准号:10640162
- 负责人:
- 金额:$ 37.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-07 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:ATP phosphohydrolaseAntineoplastic AgentsBiological AssayBrainCRISPR/Cas technologyCell Culture TechniquesCell LineCell SurvivalCell divisionCellsCentrosomeChromosomal InstabilityChromosome SegregationChromosomesClassificationClustered Regularly Interspaced Short Palindromic RepeatsCongenital AbnormalityCongressesCoupledDevelopmentEmbryoEmbryonic DevelopmentEngineeringEnhancersEnzymatic BiochemistryFluorescenceFluorescence MicroscopyFunctional disorderFutureGenerationsGenomeGeometryGoalsHumanImageImaging DeviceImpairmentInvestigationKinesinKinetochoresLengthMXD1 geneMalignant NeoplasmsMicroscopyMicrotubulesMitosisMitoticMotorPathway interactionsPharmaceutical PreparationsPharmacologyPhosphotransferasesPositioning AttributePredispositionProteasome InhibitorProteinsResistanceRoleSirolimusTestingTherapeuticTransgenic OrganismsTubulinVertebratesZebrafishcell fixingcohesionembryo cellhatchingknowledge basemutantnerve stem cellneurodevelopmentnew therapeutic targetoverexpressionprematurepreservationpreventpublic health relevancesingle moleculesmall moleculestem cell divisionstem cellstargeted agenttherapeutic targettumorigenic
项目摘要
Modified Project Summary/Abstract Section
The broad goal of this project is to understand how force generation by kinesin-related motors and dynamic microtubules controls the fidelity of chromosome segregation. Both microtubules and motors represent excellent targets for anti-cancer drugs but to make wise choices for developing therapeutics it is necessary to understand their contribution to cell division in detail. MCAK/Kif2C is a MT depolymerizing kinesin that controls MT length within the spindle and supresses chromosome instability (CIN). Using CRISPR/Cas9 engineered cells, rapamycin-dependent relocalization and long-term live imaging we have pinpointed the precise contribution that this protein makes to enhance the fidelity of chromosome segregation which will enable us to understand why this protein rescues CIN in tumorigenic cells and its future potential as a therapeutic target. MCAK/Kif2C is also strongly associated with centrosomes where it has the potential to suppress MT outgrowth and influence centrosome separation. We have identified two other poorly studied centrosome-associated kinesins, Kif25 and Kif9, that function in centrosome cohesion and centrosome satellite positioning respectively and that also impact centrosome separation and positioning. Altered centrosome positioning in cell culture has limited effects on cell viability. However, Both Kif9 and Kif25 are widely expressed in vertebrates. Because Kif25, in particular, is most highly expressed in brain it affords an opportunity to investigate the role of centrosome cohesion in vertebrate development and neural stem cell division using morpholinos directed against Kif25 introduced into early zebrafish embryos. We aim to use live and fixed-cell imaging tools and transgenic cell lines to investigate, with precision, the contribution that these kinesins make to preserving the fidelity of the genome and to long-term cell fate. Ultimately this knowledge base can be leveraged to develop new therapies that target kinesin enzymology or MT dynamics.
修改的项目摘要/摘要部分
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 }}
Linda Wordeman其他文献
Linda Wordeman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('Linda Wordeman', 18)}}的其他基金
Microtuble-dependent markers for chromosome instability
染色体不稳定的微管依赖性标记
- 批准号:
8827718 - 财政年份:2014
- 资助金额:
$ 37.93万 - 项目类别:
Microtuble-dependent markers for chromosome instability
染色体不稳定的微管依赖性标记
- 批准号:
8688658 - 财政年份:2014
- 资助金额:
$ 37.93万 - 项目类别:
相似海外基金
Delays in Acquisition of Oral Antineoplastic Agents
口服抗肿瘤药物的获取延迟
- 批准号:
9975367 - 财政年份:2020
- 资助金额:
$ 37.93万 - 项目类别:
Eliminate the difficulty of venous puncture in patients receiving antineoplastic agents - Development of a new strategy for the prevention of induration-
消除接受抗肿瘤药物的患者静脉穿刺的困难 - 制定预防硬结的新策略 -
- 批准号:
16K11932 - 财政年份:2016
- 资助金额:
$ 37.93万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Molecular mechanisms of the antineoplastic agents inhibiting DNA replication and their applications to cancer patient treatmen
抗肿瘤药物抑制DNA复制的分子机制及其在癌症患者治疗中的应用
- 批准号:
19591274 - 财政年份:2007
- 资助金额:
$ 37.93万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
PNET EXPERIMENTAL THERAPEUTICS--ANTINEOPLASTIC AGENTS AND TREATMENT DELIVERY
PNET 实验治疗——抗肿瘤药物和治疗实施
- 批准号:
6346309 - 财政年份:2000
- 资助金额:
$ 37.93万 - 项目类别:
TYROSINE KINASE INHIBITORS AS ANTINEOPLASTIC AGENTS
酪氨酸激酶抑制剂作为抗肿瘤剂
- 批准号:
2885074 - 财政年份:1999
- 资助金额:
$ 37.93万 - 项目类别:
TYROSINE KINASE INHIBITORS AS ANTINEOPLASTIC AGENTS
酪氨酸激酶抑制剂作为抗肿瘤剂
- 批准号:
6174221 - 财政年份:1999
- 资助金额:
$ 37.93万 - 项目类别: