Innovative Technologies for Stratified and Experimental Medicine

分层和实验医学的创新技术

基本信息

批准号：
MR/M009041/1
负责人：
Patrick Maxwell
金额：
$ 1863.06万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FM009041%2F1
关键词：
Innovative Technologies Stratified Experimental Medicine

项目摘要

We aim to build scientific and computing infrastructure in the School of Clinical Medicine at the University of Cambridge that will allow us i) to develop new technologies for measuring and imaging molecules in humans, and ii) to apply these technologies directly and immediately to major research programmes for understanding and treatment of cancer, metabolic disorders, and many other therapeutic areas.Our strategic vision is that many diseases, that are traditionally diagnosed and treated as if all patients with the same diagnosis were largely the same, will become increasingly stratified. We expect that advances in biomedical science will demonstrate that there are in fact many different genetic and molecular pathways to the same clinical diagnosis. This has potentially important implications for more precise targeting of treatment: more refined diagnostic stratification of patients could identify more exactly which patients were most likely to respond to specific treatments. To realise this vision, we propose to create three new high-tech facilities for clinical research in Cambridge; a Stratified Medicine Core Laboratory (SMCL), a Molecular Imaging Centre (MIC), and a High Performance Hub for Informatics (HPHI).The SMCL will allow us to measure a large number of peptides and other molecules in blood or other tissue samples with enhanced accuracy and sensitivity. The SMCL will also provide new facilities for next generation sequencing of DNA so that genetic variants driving disease can be identified in individual patients with sufficient precision and reliability to optimize diagnostic stratification and to inform clinical management immediately.The MIC will allow us to measure molecules by imaging of patients, rather than by lab analysis of tissue samples. The MIC will comprise a new whole body scanner that can simultaneously collect MRI and PET data, as well as new facilities for manufacturing and administering labeled molecules as imaging probes to patients. The new radiochemistry facilities in the MIC will allow us to produce a much larger range and volume of radioactively labeled molecules that can be detected by PET imaging. The MIC will also support the technological development of dynamic nuclear polarization (DNP). This is a radically innovative method of molecular imaging which could potentially allow us to detect labeled molecules by MRI and without exposing patients to the risks of radioactivity. We will also upgrade one of our existing MRI scanners and locate it closer to the main focus of experimental medicine research in Cambridge.The HPHI will provide the computational resources required to store and analyse the very large volumes of data produced by the SMCL and the MIC. It is also crucially important that the results of clinically actionable molecular analysis and imaging can be linked to individual patient records. This is key to "pulling through" the benefits of new technology to deliver stratified medicine in clinical practice. It is also important that the "big data" generated by the SMCL and MIC can be shared with the wider scientific community including our research partners elsewhere in the UK. We therefore propose to invest in new facilities for data storage, computational analysis, secure and ethically approved linkage of research data to clinical records, and data sharing. This computational hub will be managed as part of the University of Cambridge's new high performance computing facility.These infrastructural investments have been planned to create an integrated platform for molecular and genetic stratification of human disease. They will enhance the impact of internationally leading research groups already established in Cambridge and they are coordinated with major infrastructural programmes already funded by the University or other agencies. They will underpin a step change in our capacity to harness the potential of new technologies to deliver our strategic vision.

我们的目标是在剑桥大学临床医学院建立科学和计算基础设施，这将使我们能够 i) 开发用于测量和成像人类分子的新技术，以及 ii) 将这些技术直接立即应用于重大研究旨在了解和治疗癌症、代谢紊乱和许多其他治疗领域的计划。我们的战略愿景是，传统上诊断和治疗的许多疾病将变得越来越分层，这些疾病在传统上被诊断和治疗，就好像所有具有相同诊断的患者基本相同。我们期望生物医学的进步将证明，事实上同一临床诊断有许多不同的遗传和分子途径。这对于更精确的治疗目标具有潜在的重要意义：对患者进行更精细的诊断分层可以更准确地识别哪些患者最有可能对特定治疗产生反应。为了实现这一愿景，我们建议在剑桥创建三个新的高科技临床研究设施；分层医学核心实验室 (SMCL)、分子成像中心 (MIC) 和高性能信息学中心 (HPHI)。SMCL 将使我们能够测量血液或其他组织样本中的大量肽和其他分子提高准确性和灵敏度。 SMCL 还将提供下一代 DNA 测序的新设施，以便能够以足够的精度和可靠性在个体患者中识别驱动疾病的遗传变异，以优化诊断分层并立即为临床管理提供信息。MIC 将使我们能够通过以下方式测量分子：对患者进行成像，而不是对组织样本进行实验室分析。 MIC 将包括一个新的全身扫描仪，可以同时收集 MRI 和 PET 数据，以及用于制造和管理标记分子作为患者成像探针的新设施。 MIC 的新放射化学设施将使我们能够生产范围更大、体积更大的放射性标记分子，这些分子可以通过 PET 成像进行检测。 MIC还将支持动态核极化（DNP）的技术开发。这是一种彻底创新的分子成像方法，它可能使我们能够通过 MRI 检测标记分子，而不会让患者面临放射性风险。我们还将升级现有的一台 MRI 扫描仪，并将其放置在更靠近剑桥实验医学研究主要焦点的位置。HPHI 将提供存储和分析 SMCL 和 MIC 产生的大量数据所需的计算资源。同样至关重要的是，临床上可行的分子分析和成像结果可以与个体患者记录联系起来。这是“发挥”新技术在临床实践中提供分层医学优势的关键。同样重要的是，SMCL 和 MIC 生成的“大数据”可以与更广泛的科学界（包括我们在英国其他地方的研究合作伙伴）共享。因此，我们建议投资新设施，用于数据存储、计算分析、研究数据与临床记录的安全且经道德批准的链接以及数据共享。该计算中心将作为剑桥大学新的高性能计算设施的一部分进行管理。这些基础设施投资计划为人类疾病的分子和遗传分层创建一个综合平台。它们将增强已在剑桥建立的国际领先研究小组的影响力，并与大学或其他机构已经资助的主要基础设施项目相协调。它们将支持我们利用新技术潜力实现战略愿景的能力发生重大变化。