Maintaining Genetic and ChromosomalStability in the Mammalian Germline

维持哺乳动物种系的遗传和染色体稳定性

• 批准号: MC_UU_00007/6
• 负责人: Ian Adams
• 金额: $ 366.71万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00007%2F6
• 关键词: Maintaining; Genetic; ChromosomalStability; Mammalian; Germline

The egg and sperm cells that pass genetic information from parents to their children go through a specialised form of cell division called meiosis. Meiosis halves the number of chromosomes in the developing eggs and sperm, but mistakes during meiosis can result in embryos inheriting the wrong number of chromosomes. This can cause genetic disease and miscarriage, and is the basis of some common inherited conditions in humans such as Down Syndrome. Although we know some of the risk factors for these meiotic errors in humans, we don’t fully understand how risk factors like maternal age affects meiotic chromosomes, or how risk factors like the number of chromosomal exchanges in meiosis are normally regulated. We have previously identified new pathways operating in mice that prevent some of these meiotic mistakes from occurring in the developing eggs and sperm. The aim of this programme is to better understand how these pathways affect chromosome behaviour in meiosis in mice. We will use a combination of cultured cell lines and genetically modified mice to investigate which chromosome-associated molecules are regulated by these pathways, and to investigate if we can manipulate these pathways to reduce or prevent chromosomal abnormalities from arising in developing eggs and sperm. We hope that by understanding and manipulating these pathways in mice, we will learn more about how we might, in the future, be able to prevent chromosomal abnormalities from arising in humans.

将遗传信息从父母传递给孩子的卵细胞和精细胞经历一种特殊的细胞分裂形式，称为减数分裂。减数分裂使发育中的卵子和精子的染色体数量减半，但减数分裂过程中的错误可能导致胚胎遗传错误的染色体数量。这可能会导致遗传性疾病和流产，并且是唐氏综合症等人类常见遗传性疾病的基础。虽然我们知道人类减数分裂错误的一些风险因素，但我们并不完全了解诸如母亲年龄等风险因素如何影响减数分裂染色体，或者减数分裂中染色体交换的数量等风险因素如何正常调节。我们以前已经确定了在小鼠中运行的新途径，可以防止发育中的卵子和精子发生减数分裂错误。该计划的目的是更好地了解这些途径如何影响小鼠减数分裂中的染色体行为。我们将使用培养的细胞系和转基因小鼠的组合来研究哪些染色体相关分子受这些途径的调节，并研究我们是否可以操纵这些途径来减少或防止发育中的卵子和精子出现染色体异常。我们希望通过理解和操纵小鼠中的这些通路，我们将更多地了解我们将来如何能够预防人类染色体异常。

项目成果

Computational Tools for the Analysis of Meiotic Prophase I Images

• DOI: 10.1101/2023.11.15.567191
• 发表时间: 2024-03
• 期刊: bioRxiv
• 作者: James H. Crichton;I. Adams

A retroviral origin of vertebrate myelin

• DOI: 10.1101/2022.01.24.477350
• 发表时间: 2022-01
• 期刊: bioRxiv
• 作者: Tanay Ghosh;R. Almeida;Chao Zhao;A. Mannioui;E. Martin;Alex Fleet;Ginez Gonzalez M;D. Rowitch;K. Stott;I. Adams;B. Zalc;N. Goldman;D. Lyons;R. Franklin

Structural maturation of SYCP1-mediated meiotic chromosome synapsis through conformational remodelling by molecular adapter SYCE3

• DOI: 10.1101/2022.03.06.483192
• 发表时间: 2022-03
• 期刊: bioRxiv
• 作者: James H. Crichton;J. M. Dunce;O. Dunne;L. Salmon;Paul S. Devenney;J. Lawson;I. Adams;O. Davies

Structural maturation of SYCP1-mediated meiotic chromosome synapsis by SYCE3.

• DOI: 10.1038/s41594-022-00909-1
• 发表时间: 2023-03
• 期刊: Nature structural & molecular biology
• 影响因子: 16.8
• 作者: Crichton JH;Dunce JM;Dunne OM;Salmon LJ;Devenney PS;Lawson J;Adams IR;Davies OR
• 通讯作者: Davies OR

RNA splicing is a key mediator of tumour cell plasticity and a therapeutic vulnerability in colorectal cancer.

• DOI: 10.1038/s41467-022-30489-z
• 发表时间: 2022-05-19
• 期刊: Nature communications
• 影响因子: 16.6