Functions & Applications of a Novel Stem Cell Signalling Pathway

Findlay实验室使用尖端技术来揭开胚胎干细胞(ES)细胞信号网络(Williams等人细胞代表2016，Fernandez-Alonso等人EMBO代表2017，Fernandez-Alonso等人J Mol Biol 2017，Bustos等细胞代表2018，Fernandez-Alonso等人NAT Commum 2020，Bustos等人Dev Cell 2020)，最终我们发现ERK5通路是ES细胞多能性的令人兴奋的新调节因子。为了揭示ERK5在ES细胞中的功能，该项目将采用全球蛋白质组和磷酸蛋白质组图谱，以及RNA-SEQ和CHIP-SEQ等转录转录技术。新的ERK5底物和转录网络将使用生化和胚胎干细胞生物学方法进行鉴定和表征。进一步的目的是研究ERK5在人类患者来源的iPS细胞维持和向神经元、心肌细胞等谱系特异性分化中的功能。这项研究将在MRC蛋白磷酸化和泛素化单元(MRC-PPU)进行，MRC-PPU是研究细胞信号在健康和疾病中的作用的世界领先中心之一。学生将有机会接触到最先进的工具来剖析信号网络，并有机会通过信号转导治疗部门与支持MRC-PPU的三家主要制药公司进行互动。芬德利实验室也隶属于细胞和发育生物学部门，该部门由干细胞研究方面的世界专家组成。申请者还将与第二主管Vicky Cowling密切合作，剖析ERK5调控转录和基因表达的机制。

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.