MRC Transition Support CSF David Owen

MRC 过渡支持 CSF David Owen

• 批准号: MR/T031891/1
• 负责人: David Owen
• 金额: $ 53.73万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT031891%2F1
• 关键词: MRC; Transition; Support; CSF; David

1) OVERARCHING AIMSMicroglia - cells of the immune system that live in the brain - contain a protein called TSPO. Drugs which target TSPO change microglial behaviour and protect nerve cells in animal models of neurodegenerative disease. However, the function of TSPO is unknown. Therefore, the aim of this project is to understand how TSPO protects nerve cells, and hence to pave the way for novel treatments of neurodegenerative disease.Scientific Progress I have set up an immunology laboratory and a facility to grow human microglia from stem cells (IPS cells). I then characterised the cells and showed they behave similarly to human microglia derived from patients undergoing biopsies and hence they are fit-for-purpose. We next identified which proteins TSPO associates with, which is a vital question when trying to understand the function of a protein. We also showed how removing TSPO from the cells affects their immune function. Non-Scientific ProgressChair of NW London IVIG panel (IVIG is a lifesaving but scares resource).Invited to chair NW London Integrated GP Formulary Panel (makes decisions covering 2 million people).Paid scientific advisory board member of Nodthera and INmune Bio. Rising Star Award (ONO Pharmaceuticals - including a small grant (£91,000)).Invited to speak (expenses paid) at 4 international (highly reputable) conferences .

1)最主要的AIM小胶质细胞--生活在大脑中的免疫系统细胞--含有一种名为TSPO的蛋白质。针对TSPO的药物在神经退行性疾病的动物模型中改变小胶质细胞的行为并保护神经细胞。然而，TSPO的功能尚不清楚。因此，这个项目的目的是了解TSPO如何保护神经细胞，从而为神经退行性疾病的新疗法铺平道路。科学进展I建立了一个免疫学实验室和一个从干细胞(IPS细胞)培养人小胶质细胞的设施。然后，我描述了这些细胞的特征，并表明它们的行为类似于从接受活组织检查的患者身上提取的人类小胶质细胞，因此它们适合用于特定用途。接下来，我们确定了TSPO与哪些蛋白质相关，这是试图了解蛋白质功能时的一个关键问题。我们还展示了从细胞中去除TSPO如何影响它们的免疫功能。非科学进展伦敦西北部IVIG小组主席(IVIG是一种拯救生命但令人恐惧的资源)。受邀担任伦敦西北部综合全科医生公式小组主席(做出覆盖200万人的决策)。Paid科学顾问委员会成员Nodthera和Inmune Bio。后起之秀奖(小野制药-包括小额赠款(GB 91,000))。受邀在4个国际(声誉良好的)会议上发言(已支付费用)。

项目成果

Alzheimer's disease-related transcriptional sex differences in myeloid cells.

• DOI: 10.1186/s12974-022-02604-w
• 发表时间: 2022-10-05
• 期刊: Journal of neuroinflammation
• 影响因子: 9.3

Specific and non-specific binding of a tracer for the translocator-specific protein in schizophrenia: an [11C]-PBR28 blocking study.

• DOI: 10.1007/s00259-021-05327-x
• 发表时间: 2021-10
• 期刊: European journal of nuclear medicine and molecular imaging
• 影响因子: 9.1
• 作者: Marques TR;Veronese M;Owen DR;Rabiner EA;Searle GE;Howes OD
• 通讯作者: Howes OD

Translocator protein PET imaging in temporal lobe epilepsy: A reliable test-retest study using asymmetry index.

• DOI: 10.3389/fnimg.2023.1142463
• 发表时间: 2023
• 期刊: Frontiers in neuroimaging
• 作者: Mahmud, Mohammad;Wade, Charles;Jawad, Sarah;Hadi, Zaeem;Otoul, Christian;Kaminski, Rafal M;Muglia, Pierandrea;Kadiu, Irena;Rabiner, Eugenii;Maguire, Paul;Owen, David R;Johnson, Michael R
• 通讯作者: Johnson, Michael R

Cross-platform transcriptional profiling identifies common and distinct molecular pathologies in Lewy body diseases.

• DOI: 10.1007/s00401-021-02343-x
• 发表时间: 2021-09
• 期刊: Acta neuropathologica
• 影响因子: 12.7
• 作者: Feleke R;Reynolds RH;Smith AM;Tilley B;Taliun SAG;Hardy J;Matthews PM;Gentleman S;Owen DR;Johnson MR;Srivastava PK;Ryten M
• 通讯作者: Ryten M

Comparing the Pathology, Clinical, and Demographic Characteristics of Younger and Older-Onset Multiple Sclerosis.

比较年轻和老年发病的多发性硬化症的病理学、临​​床和人口学特征。

• DOI: 10.1002/ana.26843
• 发表时间: 2023
• 期刊: Annals of neurology
• 影响因子: 11.2
• 作者: Knowles S