Proteomic investigation of alternative splicing in the control of cell differentiation
选择性剪接控制细胞分化的蛋白质组学研究
基本信息
- 批准号:RGPIN-2017-06159
- 负责人:
- 金额:$ 1.89万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2019
- 资助国家:加拿大
- 起止时间:2019-01-01 至 2020-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Alternative splicing plays an important role in generating proteome diversity in eukaryotes, as primary messengers (pre-mRNA) turn into multiple mature messengers by inclusion and exclusion of specific sets of protein-coding exons during the process. Alternative splicing is required for cell differentiation in a wide range of biological processes. Despite its importance, the precise mechanisms controlling alternative splicing during cell differentiation remain poorly understood.******Proteomics is a powerful tool to study global protein expression, modification, and interaction in many mechanistic biological studies. To date there has been limited use of proteomics to study alternative splicing, mainly due to the lack of proper methodology. Development and application of proteomic methods to study the global splicing program and the upstream splicing regulators during cell fate changes will be essential to further our understanding of the alternative splicing mechanisms that regulate cell differentiation. ******My proposed research program seeks to develop and apply proteomic methods to delineate a general framework that mechanistically links signal transduction, splicing factors, and pre-mRNA substrates in controlling cell differentiation. We will use human pluripotent stem cells (PSC) as our model systems of cell differentiation, as they can be conveniently expanded in culture and are able to differentiate into most downstream cell types. ******We will pursue three specific aims within this proposed NSERC Discovery Grant program. First, we will develop proteomic method to identify upstream splicing regulators of key alternative splicing events that are crucial in directing PSC fate control. Second, we will develop proteomic methods to globally investigate protein splice variants in human PSC before and after differentiation initiation. Last, we will use biochemical and genetic approaches to understand the functions of splice variants and their upstream regulators in human PSC self-renewal and differentiation initiation. Through these studies, we will generate new knowledge about the alternative splicing regulatory mechanisms in eukaryotic cells. These results will also improve our understanding of stem cell and progenitor cell self-renewal and differentiation mechanisms. The proteomic methods developed in this research program can be applied to detect alternative splicing events and upstream regulators that may represent potential therapeutic targets in human diseases such as cancer and neurodegenerative diseases. Furthermore, this research program will allow my laboratory to develop talented young scientists who are crucial for Canada's sustainable economic growth fueled by continuous science and technology development.
选择性剪接在真核生物中产生蛋白质组多样性方面发挥着重要作用,因为初级信使(前 mRNA)通过在此过程中包含和排除特定的蛋白质编码外显子组而转变为多个成熟信使。在多种生物过程中,细胞分化都需要选择性剪接。尽管其重要性,但在细胞分化过程中控制选择性剪接的精确机制仍然知之甚少。 *****蛋白质组学是在许多机制生物学研究中研究整体蛋白质表达、修饰和相互作用的强大工具。迄今为止,蛋白质组学在研究选择性剪接方面的应用有限,主要是由于缺乏适当的方法。开发和应用蛋白质组学方法来研究细胞命运变化过程中的整体剪接程序和上游剪接调节因子对于进一步了解调节细胞分化的替代剪接机制至关重要。 ******我提出的研究计划旨在开发和应用蛋白质组学方法来描绘一个通用框架,该框架在控制细胞分化过程中机械地连接信号转导、剪接因子和前 mRNA 底物。我们将使用人类多能干细胞(PSC)作为细胞分化的模型系统,因为它们可以在培养物中方便地扩增,并且能够分化为大多数下游细胞类型。 ******我们将在拟议的 NSERC 发现资助计划中追求三个具体目标。首先,我们将开发蛋白质组学方法来识别关键选择性剪接事件的上游剪接调节因子,这些调节因子对于指导 PSC 命运控制至关重要。其次,我们将开发蛋白质组学方法来全面研究分化起始前后人类 PSC 中的蛋白质剪接变异。最后,我们将利用生化和遗传学方法来了解剪接变体及其上游调节因子在人类 PSC 自我更新和分化启动中的功能。通过这些研究,我们将产生关于真核细胞中选择性剪接调节机制的新知识。这些结果还将提高我们对干细胞和祖细胞自我更新和分化机制的理解。该研究项目中开发的蛋白质组学方法可用于检测可变剪接事件和上游调节因子,这些事件和上游调节因子可能代表癌症和神经退行性疾病等人类疾病的潜在治疗靶点。此外,该研究计划将使我的实验室能够培养有才华的年轻科学家,他们对于科学技术不断发展推动的加拿大可持续经济增长至关重要。
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 }}
Lu, Yu其他文献
Adolescent Bullying and Weapon Carrying: A Longitudinal Investigation
- DOI:
10.1111/jora.12469 - 发表时间:
2020-01-01 - 期刊:
- 影响因子:3.6
- 作者:
Lu, Yu;Avellaneda, Flor;Temple, Jeff R. - 通讯作者:
Temple, Jeff R.
ZDHHC5-mediated S-palmitoylation of FAK promotes its membrane localization and epithelial-mesenchymal transition in glioma.
- DOI:
10.1186/s12964-023-01366-z - 发表时间:
2024-01-17 - 期刊:
- 影响因子:8.4
- 作者:
Wang, Yang;Shen, Na;Yang, Yang;Xia, Yuan;Zhang, Wenhao;Lu, Yu;Wang, Zhicheng;Yang, Ze;Wang, Zhangjie - 通讯作者:
Wang, Zhangjie
Impact of structurally diverse polysaccharides on colonic mucin O-glycosylation and gut microbiota.
- DOI:
10.1038/s41522-023-00468-3 - 发表时间:
2023-12-11 - 期刊:
- 影响因子:9.2
- 作者:
Zhao, Tong;Zhang, Yue;Nan, Linhua;Zhu, Qing;Wang, Shukai;Xie, Yutao;Dong, Xinling;Cao, Cui;Lin, Xiaoliang;Lu, Yu;Liu, Yuxia;Huang, Linjuan;Gong, Guiping;Wang, Zhongfu - 通讯作者:
Wang, Zhongfu
The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors.
HK II在肿瘤发育及其抑制剂的研究进展中的促进作用。
- DOI:
10.3390/molecules29010075 - 发表时间:
2023-12-22 - 期刊:
- 影响因子:4.6
- 作者:
Liu, Bingru;Lu, Yu;Taledaohan, Ayijiang;Qiao, Shi;Li, Qingyan;Wang, Yuji;Nakagawa-Goto, Kyoko - 通讯作者:
Nakagawa-Goto, Kyoko
Characterization of an RNA binding protein interactome reveals a context-specific post-transcriptional landscape of MYC-amplified medulloblastoma.
- DOI:
10.1038/s41467-022-35118-3 - 发表时间:
2022-12-06 - 期刊:
- 影响因子:16.6
- 作者:
Kameda-Smith, Michelle M. M.;Zhu, Helen;Luo, En-Ching;Suk, Yujin;Xella, Agata;Yee, Brian;Chokshi, Chirayu;Xing, Sansi;Tan, Frederick;Fox, Raymond G. G.;Adile, Ashley A. A.;Bakhshinyan, David;Brown, Kevin;Gwynne, William D. D.;Subapanditha, Minomi;Miletic, Petar;Picard, Daniel;Burns, Ian;Moffat, Jason;Paruch, Kamil;Fleming, Adam;Hope, Kristin;Provias, John P. P.;Remke, Marc;Lu, Yu;Reya, Tannishtha;Venugopal, Chitra;Reimand, Juri;Wechsler-Reya, Robert J. J.;Yeo, Gene W. W.;Singh, Sheila K. K. - 通讯作者:
Singh, Sheila K. K.
Lu, Yu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('Lu, Yu', 18)}}的其他基金
Proteomic investigation of alternative splicing in the control of cell differentiation
选择性剪接控制细胞分化的蛋白质组学研究
- 批准号:
RGPIN-2017-06159 - 财政年份:2021
- 资助金额:
$ 1.89万 - 项目类别:
Discovery Grants Program - Individual
Proteomic investigation of alternative splicing in the control of cell differentiation
选择性剪接控制细胞分化的蛋白质组学研究
- 批准号:
RGPIN-2017-06159 - 财政年份:2020
- 资助金额:
$ 1.89万 - 项目类别:
Discovery Grants Program - Individual
Proteomic investigation of alternative splicing in the control of cell differentiation
选择性剪接控制细胞分化的蛋白质组学研究
- 批准号:
RGPIN-2017-06159 - 财政年份:2018
- 资助金额:
$ 1.89万 - 项目类别:
Discovery Grants Program - Individual
Proteomic investigation of alternative splicing in the control of cell differentiation
选择性剪接控制细胞分化的蛋白质组学研究
- 批准号:
RGPIN-2017-06159 - 财政年份:2017
- 资助金额:
$ 1.89万 - 项目类别:
Discovery Grants Program - Individual
相似海外基金
Mental Health and Occupational Functioning in Nurses: An investigation of anxiety sensitivity and factors affecting future use of an mHealth intervention
护士的心理健康和职业功能:焦虑敏感性和影响未来使用移动健康干预措施的因素的调查
- 批准号:
10826673 - 财政年份:2024
- 资助金额:
$ 1.89万 - 项目类别:
Disrupting Dogma: Investigating LPS Biosynthesis Inhibition as an Alternative Mechanism of Action of Aminoglycoside Antibiotics
颠覆教条:研究 LPS 生物合成抑制作为氨基糖苷类抗生素的替代作用机制
- 批准号:
10653587 - 财政年份:2023
- 资助金额:
$ 1.89万 - 项目类别:
Using Photobiomodulation to Alleviate Brain Hypoperfusion in Alzheimer's Disease
利用光生物调节缓解阿尔茨海默氏病的大脑灌注不足
- 批准号:
10656787 - 财政年份:2023
- 资助金额:
$ 1.89万 - 项目类别:
Developing a novel disease-targeted anti-angiogenic therapy for CNV
开发针对 CNV 的新型疾病靶向抗血管生成疗法
- 批准号:
10726508 - 财政年份:2023
- 资助金额:
$ 1.89万 - 项目类别:
Using proteogenomics to assess the functional impact of alternative splicing events in glioblastoma
使用蛋白质基因组学评估选择性剪接事件对胶质母细胞瘤的功能影响
- 批准号:
10577186 - 财政年份:2023
- 资助金额:
$ 1.89万 - 项目类别:
Illuminating multiplexed RNA dynamics to interrogate splicing in health and disease
阐明多重 RNA 动力学以探究健康和疾病中的剪接
- 批准号:
10713923 - 财政年份:2023
- 资助金额:
$ 1.89万 - 项目类别:
Investigate Host Gene Isoforms Contributing to HIV Persistence in Cocaine Users
研究导致可卡因吸食者中艾滋病毒持续存在的宿主基因亚型
- 批准号:
10788990 - 财政年份:2023
- 资助金额:
$ 1.89万 - 项目类别:
Developing Tools to Understand an Alternative Fate of Urate in Neurodegenerative Diseases
开发工具来了解尿酸盐在神经退行性疾病中的替代命运
- 批准号:
10668103 - 财政年份:2023
- 资助金额:
$ 1.89万 - 项目类别:
Upper airway collapsibility, loop gain and arousal threshold: an integrative therapeutic approach to obstructive sleep apnea
上气道塌陷、循环增益和唤醒阈值:阻塞性睡眠呼吸暂停的综合治疗方法
- 批准号:
10859275 - 财政年份:2023
- 资助金额:
$ 1.89万 - 项目类别:
Are apprenticeships a genuine alternative to university study? : an investigation using administrative data
学徒制真的可以替代大学学习吗?
- 批准号:
2884767 - 财政年份:2023
- 资助金额:
$ 1.89万 - 项目类别:
Studentship