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Functions & Applications of a Novel Stem Cell Signalling Pathway

功能

基本信息

批准号：
2593641
负责人：
金额：
--
依托单位：
University of Dundee
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2021
资助国家：
英国
起止时间：
2021 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2593641
关键词：
Functions Applications Novel Stem Cell

项目摘要

The Findlay lab employs cutting-edge technologies to unravel Embryonic Stem (ES) cell signalling networks (Williams et al Cell Rep 2016, Fernandez-Alonso et al EMBO Rep 2017, Fernandez-Alonso et al J Mol Biol 2017, Bustos et al Cell Rep 2018, Fernandez-Alonso et al Nat Commum 2020, Bustos et al Dev Cell 2020), culminating in our discovery of the ERK5 pathway as an exciting new regulator of ES cell pluripotency. In order to uncover functions of ERK5 in ES cells, this project will deploy global proteomic and phosphoproteomic profiling, and transcriptomic technologies such as RNA-SEQ and ChIP-SEQ. Novel ERK5 substrates and transcriptional networks will be identified and characterised using biochemical and ES cell biology approaches. A further aim is to investigate functions of ERK5 in human patient-derived iPS cell maintenance and lineage-specific differentiation to neurons, cardiomyocytes etc. This research will be undertaken in the MRC Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU), one of the world's leading centres studying the role of cell signalling in health and disease. Students will have access to state-of-the-art tools to dissect signalling networks, and opportunity for interaction with three major Pharmaceutical companies that support the MRC-PPU via the Division of Signal Transduction Therapy. The Findlay lab is also affiliated with the Division of Cell and Developmental Biology, which comprises world experts in stem cell research. The applicant will also work closely with second supervisor Vicky Cowling to dissect mechanisms by which ERK5 regulates transcription and gene expression.

Findlay实验室采用尖端技术来解开胚胎干细胞（ES）信号网络（威廉姆斯等人Cell Rep 2016，Fernando-Alonso等人EMBO Rep 2017，Fernando-Alonso等人J Mol Biol 2017，Buffalo等人Cell Rep 2018，Fernando-Alonso等人Nat Commum 2020，Buffalo等人Dev Cell 2020），最终我们发现ERK 5通路是ES细胞多能性的一个令人兴奋的新调节因子。为了揭示ERK 5在ES细胞中的功能，该项目将部署全球蛋白质组学和磷酸化蛋白质组学分析，以及转录组学技术，如RNA-SEQ和ChIP-SEQ。新型ERK 5底物和转录网络将使用生物化学和ES细胞生物学方法进行鉴定和表征。另一个目的是研究ERK 5在人类患者来源的iPS细胞维持和谱系特异性分化为神经元，心肌细胞等的功能。这项研究将在MRC蛋白磷酸化和泛素化单位（MRC-PPU）进行，该单位是世界领先的研究细胞信号传导在健康和疾病中的作用的中心之一。学生将有机会获得最先进的工具来剖析信号网络，并有机会与三家主要的制药公司互动，通过信号转导治疗部门支持MRC-PPU。芬德利实验室还隶属于细胞和发育生物学部门，该部门由世界干细胞研究专家组成。申请人还将与第二主管Vicky Cowling密切合作，剖析ERK 5调节转录和基因表达的机制。