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，这将使我们能够i)开发用于测量和成像人体分子的新技术，ii)将这些技术直接和立即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项目。我们的战略愿景是，许多传统上被诊断和治疗的疾病，似乎所有诊断相同的患者在很大程度上都是一样的，这些疾病将变得越来越分层。我们期望生物医学科学的进步将证明，实际上有许多不同的遗传和分子途径可以达到相同的临床诊断。这对于更精确地靶向治疗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确定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，我们建议在剑桥建立三个新的高科技临床研究设施；一个分层医学核心实验室（SMCL），一个分子成像中心（MIC）和一个高性能信息学中心（HPHI）。SMCL将使我们能够以更高的准确性和灵敏度测量血液或其他组织样品中的大量肽和其他分子。SMCL还将为下一代DNA测序提供新的设施，以便能够在个体患者中以足够的精度和可靠性识别导致疾病的遗传变异，以优化诊断分层并立即通知临床管理。MIC将允许我们通过对患者的成像来测量分子，而不是通过对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MRI和PET数据，以及用于制造和给患者使用标记分子作为成像探针的新设备。MIC的新放射化学设备将允许我们生产更大范围和体积的放射性标记分子，这些分子可以通过PET成像检测到。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，可以让我们通过核磁共振检测标记分子，而不会让患者暴露在放射性的风险中。我们还将升级现有的一台核磁共振扫描仪，并将其安置在离剑桥实验医学研究中心更近的地方。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，临床可操作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“利用”新技术在临床实践中提供分层药物的关键。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合作伙伴。因此，我们建议投资于数据存储、计算分析、安全和伦理批准的研究数据与临床记录的链接以及数据共享的新设施。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。这些基础设施投资计划的目的是为人类疾病的分子和遗传分层建立一个综合平台。这些项目将增强已经在剑桥建立的国际领先研究小组的影响力，并与剑桥大学或其他机构已经资助的主要基础设施项目进行协调。它们将巩固我们利用新技术潜力实现战略愿景的能力。

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.