Dementias Platform UK Stem Cell Partnership

痴呆症平台英国干细胞合作伙伴关系

• 批准号: MR/N013255/1
• 负责人: Siddharthan Chandran
• 金额: $ 155.55万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN013255%2F1
• 关键词: Dementias; Platform; UK; Stem; Cell

A major hurdle to developing new treatments for dementias and other neurodegenerative disorders is the practical and ethical barriers to undertaking brain research in people. However, it is now possible to turn cells from skin biopsies or blood samples into stem cells, which can be grown in a dish in the lab. In turn, the stem cells can be differentiated into any cell type, including brain cells. This allows study of the cell processes affected in dementia and other neurodegenerative diseases in human cells, and has potential in identifying and testing new therapies.This proposal brings together six UK stem cell Centres recently supported by the MRC Dementias Platform UK (Cambridge, Cardiff, Edinburgh, Manchester, Oxford and University College London). This Dementia Stem Cell Network will provide a step change in UK dementia stem cell research and feed into drug discovery initiatives to find novel dementia treatments. Our proposed Partnership will significantly increase the capacity, competitiveness and effective use of resources of UK dementia stem cell research by helping us work together as a coordinated stem cell network.The technology involved in producing brain cells from stem cells is relatively new and evolving at a rapid pace. The Partnership will create a unique, deeply studied collection of cells donated by volunteers with dementia, plus from healthy individuals to compare them against. These cells can be grown in the lab indefinitely, and will form a global and powerful stem cell research resource. Critically, the Partnership will develop and validate protocols that will be harmonised across the network. In this way we can work together using state-of-the-art automated and large-scale technology to understand the biology of dementia. Our goal is to find new markers and develop robust tests for dementia that will accelerate the search for new drug treatments by pharmaceutical companies.This proposal will deliver this programme of research and resources by appointing and training four highly skilled Network Technical Scientists. Each will be dedicated to specific scientific techniques and goals, but share expertise and findings across the Partnership and beyond. The Partnership will also produce a training programme for PhD students, who will work across at least two Centres to address important questions about dementia/neurodegenerative disease. These two programmes will future-proof the Dementia Stem Cell Network and MRC investment by equipping the UK with researchers highly skilled in stem cell technologies who will participate in multi-site interdisciplinary research. Through the Network Technical Scientists and PhD students, we will reach out to other researchers in the UK with regular meetings to involve new sites in this collaborative venture.In summary, the Partnership will create unique shared resources and expertise to drive joined-up UK-wide dementia research with the goal of identifying new disease modifying treatments.

开发痴呆症和其他神经退行性疾病的新疗法的一个主要障碍是进行人类大脑研究的实际和伦理障碍。然而，现在可以将皮肤活检或血液样本中的细胞转化为干细胞，这些干细胞可以在实验室的培养皿中生长。反过来，干细胞可以分化成任何细胞类型，包括脑细胞。这一提议汇集了最近由MRC痴呆症平台英国支持的六个英国干细胞中心（剑桥、卡迪夫、爱丁堡、曼彻斯特、牛津和伦敦大学学院）。这个痴呆症干细胞网络将为英国痴呆症干细胞研究提供一个步骤，并为药物发现计划提供资金，以寻找新的痴呆症治疗方法。我们提议的合作伙伴关系将大大提高英国痴呆症干细胞研究的能力、竞争力和资源的有效利用，帮助我们作为一个协调的干细胞网络共同努力。该合作伙伴关系将创建一个独特的，深入研究的细胞收集与痴呆症志愿者捐赠，加上从健康的个人比较。这些细胞可以在实验室中无限期地生长，并将形成一个全球性的强大的干细胞研究资源。至关重要的是，该伙伴关系将开发和验证将在整个网络中协调的协议。通过这种方式，我们可以使用最先进的自动化和大规模技术来了解痴呆症的生物学。我们的目标是找到新的标记物，并开发强大的痴呆症测试，这将加速制药公司寻找新的药物治疗。该提案将通过任命和培训四名高技能的网络技术科学家来提供这一研究和资源计划。每个小组将致力于具体的科学技术和目标，但在伙伴关系内外分享专门知识和研究结果。该伙伴关系还将为博士生制定一项培训计划，他们将在至少两个中心工作，以解决有关痴呆症/神经退行性疾病的重要问题。这两个项目将为痴呆症干细胞网络和MRC投资提供未来证明，为英国配备在干细胞技术方面具有高度技能的研究人员，他们将参与多地点的跨学科研究。通过网络技术科学家和博士生，我们将与英国的其他研究人员定期举行会议，让新的研究地点参与这项合作事业。总之，该伙伴关系将创造独特的共享资源和专业知识，以推动联合起来的英国范围内的痴呆症研究，目标是确定新的疾病改善治疗方法。

项目成果

Cell-autonomous immune dysfunction driven by disrupted autophagy in C9orf72-ALS iPSC-derived microglia contributes to neurodegeneration.

• DOI: 10.1126/sciadv.abq0651
• 发表时间: 2023-04-21
• 期刊: Science advances
• 影响因子: 13.6

HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS.

HNRNPK 通过抵消 C9orf72 ALS 中的 DNA 损伤来减轻 RNA 毒性。

• DOI: 10.1007/s00401-022-02471-y
• 发表时间: 2022-09
• 期刊: Acta neuropathologica
• 影响因子: 12.7

Functional Studies of Missense TREM2 Mutations in Human Stem Cell-Derived Microglia.

人类干细胞来源的小胶质细胞错义 TREM2 突变的功能研究。

• DOI: 10.17863/cam.23848
• 发表时间: 2018
• 作者: Brownjohn P

Remyelination varies between and within lesions in multiple sclerosis following bexarotene.

• DOI: 10.1002/acn3.51662
• 发表时间: 2022-10
• 期刊: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
• 影响因子: 5.3
• 作者: Brown, J. William L.;Prados, Ferran;Altmann, Daniel R.;Kanber, Baris;Stutters, Jonathan;Cunniffe, Nick G.;Jones, Joanne L.;Georgieva, Zoya G.;Needham, Edward J.;Daruwalla, Cyrus;Wheeler-Kingshott, Claudia Gandini;Connick, Peter;Chandran, Siddharthan;Franklin, Robin;MacManus, David;Samson, Rebecca;Coles, Alasdair;Chard, Declan
• 通讯作者: Chard, Declan

Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer's Disease

表型筛选鉴定阿尔茨海默病人类干细胞模型中淀粉样前体蛋白加工的调节剂

• DOI: 10.17863/cam.9285
• 发表时间: 2017
• 作者: Brownjohn P