Multimodal, multiscale functional tissue state imaging

Human biology is highly complex and will never be understood by analysing individual aspects in isolation. This can only be achieved through combining advanced imaging techniques that simultaneously capture the breadth of spatial and temporal scales that make up a cell, tissue and organism. Advances in super-resolution and medical imaging technologies, spatial ‘omics’ and machine learning are providing new insight into tissue and cell composition and organisation. Massive untapped potential exists in developing and combining these scale- and modality-crossing technologies and computational methods to answer the most important and challenging research questions in health and disease. However, these imaging domains have thus far largely operated in siloes, significantly limiting the potential for new biological discovery.

Our ambitious technology-driven programme combines expertise in cell biology, medicine, physics, engineering and computational analysis/modelling with advanced spatial experimental technologies to enable multimodal interrogation of 3D functional human cell/tissue state. We will integrate organ-level structural and biomechanical MRI data in patients with matched analysis in ex-vivo live tissue samples. This will be coupled with dynamic optical and spectroscopy-based imaging to reveal metabolic states and cell-cell interactions. Complementary high-resolution spatial approaches in the same tissues post-fixation will reveal the transcriptome, lipidome, metallome and nanoscale organisation of up to 100 target proteins. Advanced computational tools will integrate these diverse data types and scales to enable quantitative understanding and interrogation of mechanistic spatial human biology in context. Our technological advances will provide unprecedented insight into disease-causing transition points and reveal new tractable targets for therapeutic intervention.