The relationship between somatic structural alteration of the genome and healthy ageing

基因组体细胞结构改变与健康衰老的关系

• 批准号: 1902605
• 金额: --
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Studentship
• 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=studentship-1902605
• 关键词: relationship; between; somatic; structural; alteration

It is increasingly clear that somatic mutations accrue steadily in ageing tissues. However, precisely how this relates to healthy ageing is unknown, and the molecular and cellular mechanisms that cause somatic mutation in otherwise healthy tissue remain poorly defined. Here, we propose to investigate the accrual of structural alterations (SAs) in ageing human colon. We will determine the spectrum of SA that is consistent with healthy ageing (e.g. the SAs that can accrue without leading to a pathology), and profile the size, type and rate of SA accrual to reveal the underlying molecular and cellular mechanisms that underpin 'healthy' human somatic mutagenesis.

越来越明显的是，体细胞突变在衰老组织中稳步积累。然而，这与健康衰老的确切关系尚不清楚，并且在其他健康组织中引起体细胞突变的分子和细胞机制仍不清楚。在这里，我们建议研究衰老人类结肠中结构改变（SA）的累积情况。我们将确定与健康衰老相一致的SA谱（例如，可以在不导致病理的情况下累积的SA），并分析SA累积的大小、类型和速率，以揭示支持“健康”人类体细胞突变的潜在分子和细胞机制。

项目成果

Assessment of the evolutionary consequence of putative driver mutations in colorectal cancer with spatial multiomic data

• DOI: 10.1101/2021.07.14.451265
• 发表时间: 2021-07
• 期刊: bioRxiv
• 作者: Timon Heide;J. Househam;George D. Cresswell;I. Spiteri;Claire Lynn;C. Kimberley;M. Mossner;L. Zapata;C. Gabbutt;Daniele Ramazzotti;Bingjie Chen;J. Fernández-Mateos;C. James;A. Vinceti;A. Berner;Melissa Schmidt;E. Lakatos;A. Baker;D. Nichol;Helena Costa;Miriam Mitchinson;B. Werner;F. Iorio;M. Jansen;Chris P. Barnes;G. Caravagna;D. Shibata;J. Bridgewater;M. Rodríguez-Justo;L. Magnani;T. Graham;A. Sottoriva

Evolutionary dynamics of 1,976 lymphoid malignancies predict clinical outcome

• DOI: 10.1101/2023.11.10.23298336
• 发表时间: 2023-11
• 作者: C. Gabbutt;M. Duran-Ferrer;H. Grant;D. Mallo;F. Nadeu;J. Househam;N. Villamor;O. Krali

Fluctuating methylation clocks for cell lineage tracing at high temporal resolution in human tissues.

• DOI: 10.1038/s41587-021-01109-w
• 发表时间: 2022-05
• 期刊: NATURE BIOTECHNOLOGY
• 影响因子: 46.9
• 作者: Gabbutt, Calum;Schenck, Ryan O.;Weisenberger, Daniel J.;Kimberley, Christopher;Berner, Alison;Househam, Jacob;Lakatos, Eszter;Robertson-Tessi, Mark;Martin, Isabel;Patel, Roshani;Clark, Susan K.;Latchford, Andrew;Barnes, Chris P.;Leedham, Simon J.;Anderson, Alexander R. A.;Graham, Trevor A.;Shibata, Darryl
• 通讯作者: Shibata, Darryl

Lineage tracing in human tissues.

• DOI: 10.1002/path.5911
• 发表时间: 2022-07
• 期刊: The Journal of pathology

Phenotypic plasticity and genetic control in colorectal cancer evolution.

• DOI: 10.1038/s41586-022-05311-x
• 发表时间: 2022-11
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Househam, Jacob;Heide, Timon;Cresswell, George D.;Spiteri, Inmaculada;Kimberley, Chris;Zapata, Luis;Lynn, Claire;James, Chela;Mossner, Maximilian;Fernandez-Mateos, Javier;Vinceti, Alessandro;Baker, Ann-Marie;Gabbutt, Calum;Berner, Alison;Schmidt, Melissa;Chen, Bingjie;Lakatos, Eszter;Gunasri, Vinaya;Nichol, Daniel;Costa, Helena;Mitchinson, Miriam;Ramazzotti, Daniele;Werner, Benjamin;Iorio, Francesco;Jansen, Marnix;Caravagna, Giulio;Barnes, Chris P.;Shibata, Darryl;Bridgewater, John;Rodriguez-Justo, Manuel;Magnani, Luca;Sottoriva, Andrea;Graham, Trevor A.
• 通讯作者: Graham, Trevor A.