Innovative Technologies for Stratified and Experimental Medicine

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，使我们能够i)开发测量和成像人类分子的新技术，以及ii)直接和立即将这些技术应用于了解和治疗癌症、代谢紊乱和许多其他治疗领域的主要研究计划。我们的战略愿景是，许多疾病将变得越来越分层，这些疾病传统上被诊断和治疗，就像所有诊断相同的患者基本上是一样的。我们预计，生物医学科学的进步将证明，事实上，对于同一临床诊断，存在许多不同的遗传和分子途径。这对更精确的治疗目标具有潜在的重要意义：更精细的患者诊断分层可以更准确地确定哪些患者最有可能对特定的治疗产生反应。为了实现这一愿景，我们建议在剑桥建立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将使我们能够以更高的准确度和灵敏度测量血液或其他组织样本中的大量多肽和其他分子。SMCL还将为下一代DNA测序提供新的设施，以便能够以足够的精确度和可靠性在单个患者中识别导致疾病的基因变异，以优化诊断分层并立即向临床管理提供信息。MIC将允许我们通过患者的成像来测量分子，而不是通过组织样本的实验室分析。MIC将包括一个新的全身扫描仪，可以同时收集核磁共振和正电子发射计算机断层扫描数据，以及制造和给患者使用标记分子作为成像探针的新设施。MIC的新放射化学设施将使我们能够生产更大范围和更大体积的放射性标记分子，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)技术的开发。这是一种彻底创新的分子成像方法，可能使我们能够通过核磁共振检测标记的分子，而不会使患者暴露在辐射风险中。我们还将升级现有的一台核磁共振扫描仪，使其更接近剑桥实验医学研究的主要重点。HPHI将提供所需的计算资源，以存储和分析SMCL和MIC产生的大量数据。同样重要的是，临床上可操作的分子分析和成像的结果可以与个别患者的记录联系起来。这是在临床实践中“渡过”提供分层医学的新技术好处的关键。同样重要的是，SMCL和MIC产生的“大数据”可以与更广泛的科学界共享，包括我们在英国其他地方的研究伙伴。因此，我们建议投资于新的设施，用于数据存储、计算分析、安全和经伦理批准的研究数据与临床记录的联系，以及数据共享。这个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。这些基础设施投资的计划是为人类疾病的分子和基因分层创建一个综合平台。它们将加强已经在剑桥设立的国际领先研究小组的影响，并与已经由剑桥大学或其他机构资助的主要基础设施方案进行协调。它们将巩固我们利用新技术的潜力来实现我们的战略愿景的能力的一步变化。

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.