Innovative Technologies for Stratified and Experimental Medicine

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.

The vision is to use the explanatory and predictive power of genetics, biomolecular assays, and molecular imaging, to refine diagnostic and therapeutic stratification of patients with cancer, metabolic, neuroscience, cardiovascular and musculoskeletal disorders. To do this, we are seeking capital investment in 3 coordinated and strategically important areas for innovative technology and stratified medicine in Cambridge:
1) Stratified Medicine Core Laboratory: will deliver high-throughput, clinically actionable, sensitive and precise measures of multiple pathophysiologically important biomolecules. The SMCL will use new mass spectrometry immuno-assays for a wide range of peptides; extended capacity for existing multiplex assays; and next generation sequencing for deep genotyping.
2) Molecular Imaging Centre: will pioneer clinical translation of new technologies, such as dynamic nuclear polarization imaging and simultaneous PET/MRI imaging of radioligand binding (PET) combined with MRI markers of local tissue structure and function. The MIC will provide pharmacy support for quality controlled production and administration of PET radioligands and hyperpolarized molecules for DPN imaging. It will also include some enhanced capacity for 3T MRI in stratified and experimental medicine, optical imaging of epithelial dysplasia and neoplasia, and cell tracking in regenerative medicine.
3) High Performance Hub for Informatics: will deliver storage, analysis, sharing, and NHS clinical linkage, for the large volumes of complex data that will be generated by the SMCL and the MIC. This integrative computational hub will link together the two key biomedical platforms and provide the principal University portal for clinical "pull through" of stratified medicine to and from individual patient records in the NHS.
These investments will leverage international research strengths in Cambridge and are aligned with major investments by Cambridge University Health Partners.

No impact summary is required for applications to the Clinical Research Infrastructure call.