Molecular Mechanisms of Cell Death

细胞死亡的分子机制

• 批准号: MC_UU_00025/4
• 负责人: Marion MacFarlane
• 金额: $ 396.02万
• 依托单位: University of Cambridge
• 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_00025%2F4
• 关键词: Molecular; Mechanisms; Cell; Death

Diseases such as cancer and neurodegenerative disorders are characterised by a significant alteration in the total number of cells within the tissue. This may result from increased division of cells and/or may arise from a defect in cell death regulation. In tissues, such as the lymphoid system or the colon, cell death is very important as it controls the total number of cells within that tissue, whereas in the nervous system inappropriate cell death is catastrophic. Consequently, cell death in these situations is tightly controlled and often occurs in an ordered manner by a process called ‘apoptosis’, or a more recently identified mode of cell death termed ‘necroptosis’. We are studying these cell death processes because to successfully treat many diseases (e.g. cancer) it is important that we find ways to switch ‘ON’ cell death. However, it is crucial to first understand the basic mechanisms that regulate cell death in order to identify ways of selectively killing target cells while leaving most healthy cells unharmed. We are therefore trying to understand the fundamental mechanisms that regulate the response of target cells and normal cells to cytotoxic agents, as this will help in establishing the ideal choice agents for the treatment of disease. Our aim is to establish better predictive models of mitochondrial toxicity, providing mechanistic frameworks to facilitate safer drug development and potentially alleviate the toxic effects of existing treatments.

癌症和神经退行性疾病等疾病的特征是组织内细胞总数的显著变化。这可能是由于细胞分裂增加和/或细胞死亡调节的缺陷造成的。在淋巴系统或结肠等组织中，细胞死亡是非常重要的，因为它控制着组织中的细胞总数，而在神经系统中，不适当的细胞死亡是灾难性的。因此，在这些情况下，细胞死亡受到严格的控制，并通常通过一种称为“细胞凋亡”的过程或最近发现的一种称为“坏死性下垂”的细胞死亡模式以有序的方式发生。我们正在研究这些细胞死亡过程，因为要成功治疗许多疾病(例如癌症)，重要的是我们要找到打开细胞死亡的方法。然而，首先了解调节细胞死亡的基本机制是至关重要的，这样才能确定选择性杀死靶细胞的方法，同时使大多数健康细胞不受损害。因此，我们正试图了解调控靶细胞和正常细胞对细胞毒剂反应的基本机制，因为这将有助于建立治疗疾病的理想选择药物。我们的目标是建立更好的线粒体毒性预测模型，提供机制框架，促进更安全的药物开发，并潜在地减轻现有治疗方法的毒性影响。

项目成果

Characterisation of FADD interactome reveals novel insights into FADD recruitment and signalling at the Death Inducing Signalling Complex (DISC)

FADD 相互作用组的表征揭示了对 FADD 招募和死亡诱导信号复合体 (DISC) 信号传导的新见解

• DOI: 10.1101/2021.03.25.436271
• 发表时间: 2021
• 作者: Fox J

Asbestos: Modern Insights for Toxicology in the Era of Engineered Nanomaterials

• DOI: 10.1021/acs.chemrestox.8b00146
• 发表时间: 2018-10-01
• 期刊: CHEMICAL RESEARCH IN TOXICOLOGY
• 影响因子: 4.1
• 作者: Felley-Bosco, Emanuela;MacFarlane, Marion
• 通讯作者: MacFarlane, Marion

Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells.

• DOI: 10.1038/s41419-023-06240-x
• 发表时间: 2023-11-08
• 期刊: CELL DEATH & DISEASE
• 影响因子: 9
• 作者: Chrisochoidou, Yakinthi;Roy, Rajat;Farahmand, Pooyeh;Gonzalez, Guadalupe;Doig, Jennifer;Krasny, Lukas;Rimmer, Ella F.;Willis, Anne E.;MacFarlane, Marion;Huang, Paul H.;Carragher, Neil O.;Munro, Alison F.;Murphy, Daniel J.;Veselkov, Kirill;Seckl, Michael J.;Moffatt, Miriam F.;Cookson, William O. C.;Pardo, Olivier E.
• 通讯作者: Pardo, Olivier E.

N-glycosylation of mouse TRAIL-R restrains TRAIL-induced apoptosis.

• DOI: 10.1038/s41419-018-0544-7
• 发表时间: 2018-05-01
• 期刊: Cell death & disease
• 影响因子: 9
• 作者: Estornes Y;Dondelinger Y;Weber K;Bruggeman I;Peall A;MacFarlane M;Lebecque S;Vandenabeele P;Bertrand MJM
• 通讯作者: Bertrand MJM

TAp73 regulates mitochondrial dynamics and multiciliated cell homeostasis through an OPA1 axis

• DOI: 10.1101/2023.03.23.533672
• 发表时间: 2023-03
• 期刊: bioRxiv
• 作者: Niall Buckley;A. Craxton;Xiao-Ming Sun;Emanuele Panatta;L. Piñón;Jaime Llodrá;N. Morone;I. Amelio;G. Melino;L. Martins;M. MacFarlane