Establishing and maintaining regulatory competency in the human genome.

建立和维持人类基因组的监管能力。

• 批准号: BB/R002851/1
• 负责人: Andrew Sharrocks
• 金额: $ 69.31万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR002851%2F1
• 关键词: Establishing; maintaining; regulatory; competency; human

As we age, we lose the capacity to repair damaged tissues and organs. One reason for this is due to the loss of a specialised set of cells known as stem cells. These cells have the capability of restoring damaged cells and have the potential to change their identity to produce multiple different cell types. This property has led researchers to try to use these cells in regenerative medicine to make cells in the laboratory which can replace damaged cells in our body. However to undertake this process it is important to understand how stem cells can change into other cell types. Part of the answer to this, is a change in how their control systems are wired, and how their DNA is packaged up. This project will investigate how a molecular switch, known as the FOXK2-SIN3A protein complex, contributes to this rewiring process. We will conduct our studies in human embryonic stem cells and examine the molecular events that occur as these cells change fate to create different cell types. Our findings will help us understand how stem cells can change their identity, and potentially will provide us with mechanistic information that enables us to both improve this process for therapeutic benefit and to understand how age related diseases develop.

随着年龄的增长，我们失去修复受损组织和器官的能力。造成这种情况的一个原因是由于一组称为干细胞的特殊细胞的丢失。这些细胞具有恢复受损细胞的能力，并有可能改变其身份以产生多种不同的细胞类型。这一特性促使研究人员尝试在再生医学中使用这些细胞，在实验室中制造可以替代我们体内受损细胞的细胞。然而，要进行这一过程，了解干细胞如何转变为其他细胞类型非常重要。解决这个问题的部分原因是改变控制系统的接线方式以及 DNA 的封装方式。该项目将研究被称为 FOXK2-SIN3A 蛋白质复合物的分子开关如何参与这一重新布线过程。我们将在人类胚胎干细胞中进行研究，并检查这些细胞改变命运以产生不同细胞类型时发生的分子事件。我们的研究结果将帮助我们了解干细胞如何改变其身份，并有可能为我们提供机制信息，使我们能够改进这一过程以获得治疗效果，并了解与年龄相关的疾病是如何发展的。

项目成果

The forkhead transcription factor FOXK2 premarks lineage-specific genes in human embryonic stem cells for activation during differentiation.

• DOI: 10.1093/nar/gkaa1281
• 发表时间: 2021-02-22
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Ji Z;Li Y;Liu SX;Sharrocks AD
• 通讯作者: Sharrocks AD

SUMOylation modulates FOXK2-mediated paclitaxel sensitivity in breast cancer cells.

• DOI: 10.1038/s41389-018-0038-6
• 发表时间: 2018-03-13
• 期刊: Oncogenesis
• 影响因子: 6.2
• 作者: Nestal de Moraes G;Ji Z;Fan LY;Yao S;Zona S;Sharrocks AD;Lam EW
• 通讯作者: Lam EW

Correction to article "The forkhead transcription factor FOXK2 premarks lineage-specific genes in human embryonic stem cells for activation during differentiation''.

• DOI: 10.1093/nar/gkab221
• 发表时间: 2021-04-19
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Ji Z;Li Y;Liu SX;Sharrocks AD
• 通讯作者: Sharrocks AD