Defining the role of STAT1 acetylation in adaptive immunity.

定义 STAT1 乙酰化在适应性免疫中的作用。

• 批准号: MR/L006197/1
• 负责人: James Thaventhiran
• 金额: $ 144.5万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL006197%2F1
• 关键词: Defining; role; STAT1; acetylation; adaptive

The immune system works by recognising pathogens as foreign and initiating a response that destroys the invader. In auto-immune disease, however, it is the host that is mistakenly thought to be foreign and so destroyed by the subsequent immune response. Both immune and auto-immune responses are dependent on an incredible expansion (>10,000fold) in the number of cells capable of recognising what is foreign. This expansion in number occurs by cellular proliferation. What is surprising is that such proliferation still occurs in environments that we would expect to be anti-proliferative because of their high levels of the anti-pathogen protein, interferon (IFN). This project tests the hypothesis that this proliferation can occur because the cells of the immune system modify the IFN signalling molecule STAT1. Experiments will test whether blocking this step prevents both protective immune responses and protects against the autoimmune disease, SLE. These experiments will also generate the materials necessary to test whether HIV owes part of its infectious success to its exploitation of this mechanism. The overall aim of the project is to reduce to a single biochemical event the complex physiological reactions that drive both immune protection and autoimmunity, in order to open new avenues for treatments.

免疫系统通过识别外来病原体并启动摧毁入侵者的反应来工作。然而，在自身免疫性疾病中，是宿主被错误地认为是外来的，因此被随后的免疫反应摧毁。免疫和自身免疫反应都依赖于能够识别外来物的细胞数量的惊人扩增（> 10，000倍）。这种数量上的扩张是通过细胞增殖发生的。令人惊讶的是，这种增殖仍然发生在我们预期是抗增殖的环境中，因为它们的抗病原体蛋白质干扰素（IFN）水平高。该项目测试的假设，这种增殖可以发生，因为免疫系统的细胞修改IFN信号分子STAT1。实验将测试阻断这一步骤是否既能阻止保护性免疫反应，又能防止自身免疫性疾病SLE。这些实验还将产生必要的材料，以测试艾滋病毒是否将其感染成功的一部分归功于其利用这一机制。该项目的总体目标是将驱动免疫保护和自身免疫的复杂生理反应减少到单一的生化事件，以开辟新的治疗途径。

项目成果

CXCR4 inhibition in human pancreatic and colorectal cancers induces an integrated immune response.

• DOI: 10.1073/pnas.2013644117
• 发表时间: 2020-11-17
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Biasci D;Smoragiewicz M;Connell CM;Wang Z;Gao Y;Thaventhiran JED;Basu B;Magiera L;Johnson TI;Bax L;Gopinathan A;Isherwood C;Gallagher FA;Pawula M;Hudecova I;Gale D;Rosenfeld N;Barmpounakis P;Popa EC;Brais R;Godfrey E;Mir F;Richards FM;Fearon DT;Janowitz T;Jodrell DI
• 通讯作者: Jodrell DI

Inborn errors of IL-6 family cytokine responses.

• DOI: 10.1016/j.coi.2021.04.007
• 发表时间: 2021-10
• 期刊: Current opinion in immunology
• 影响因子: 7
• 作者: Chen YH;Spencer S;Laurence A;Thaventhiran JE;Uhlig HH
• 通讯作者: Uhlig HH

Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report.

• DOI: 10.1038/s41467-020-19761-2
• 发表时间: 2020-12-14
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Buckland MS;Galloway JB;Fhogartaigh CN;Meredith L;Provine NM;Bloor S;Ogbe A;Zelek WM;Smielewska A;Yakovleva A;Mann T;Bergamaschi L;Turner L;Mescia F;Toonen EJM;Hackstein CP;Akther HD;Vieira VA;Ceron-Gutierrez L;Periselneris J;Kiani-Alikhan S;Grigoriadou S;Vaghela D;Lear SE;Török ME;Hamilton WL;Stockton J;Quick J;Nelson P;Hunter M;Coulter TI;Devlin L;CITIID-NIHR COVID-19 BioResource Collaboration;MRC-Toxicology Unit COVID-19 Consortium;Bradley JR;Smith KGC;Ouwehand WH;Estcourt L;Harvala H;Roberts DJ;Wilkinson IB;Screaton N;Loman N;Doffinger R;Lyons PA;Morgan BP;Goodfellow IG;Klenerman P;Lehner PJ;Matheson NJ;Thaventhiran JED
• 通讯作者: Thaventhiran JED

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

端粒：一种倍性 - 敏锐的方法，用于从整个基因组测序数据中估算端粒长度。

• DOI: 10.1038/s41598-017-14403-y
• 发表时间: 2018-01-22
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Farmery JHR;Smith ML;NIHR BioResource - Rare Diseases;Lynch AG
• 通讯作者: Lynch AG

Successful treatment of COVID-19 with remdesivir in the absence of humoral immunity

在缺乏体液免疫的情况下使用瑞德西韦成功治疗 COVID-19

• DOI: 10.21203/rs.3.rs-79022/v1
• 发表时间: 2020
• 作者: Buckland M