Nanoscale X-ray tissue imaging: understanding the pathophysiology of hepatitis E infection

A driving force behind biomedical innovation lies in disease prevention, diagnosis and treatment. This requires a comprehensive understanding of how pathogens exploit living organisms across molecular, cellular, organismal, and population levels. Treatment of disease often relies upon interventions that restore the normal structure and function of cells. However, it is currently challenging to visualise and quantify detailed cellular changes within whole tissues in response to disease. Soft X-ray microscopy is a novel, exciting imaging modality which enables detailed structural and chemical imaging of whole cells without fixation or dyes. This technique is currently used to image cultured cells, but has yet to be applied to the examination of cells within the intricate 3D architecture of tissue with its complex cell-cell interactions. Imaging of diseased tissue in this way is crucial to gain meaningful insight into disease mechanisms, while remaining complementary to other imaging modalities and biological assays. Project NanoX aims to tackle this challenge, by merging the skillsets of a world-leading team with synergistic expertise in infectious disease, physics and structural biology to pioneer several innovations – (i) a targeted micro-biopsy tool for rapid tissue extraction for soft X-ray microscopy, (ii) high-throughput nano-resolution 3D imaging of tissues, (iii) novel integrative data mining approaches, and (iv) unprecedented insights into the pathogenesis of hepatitis E virus (HEV), an important emerging zoonotic viral infection with no specific therapies or vaccines, in healthy and immune-compromised individuals. The scientific and technological innovations that will be developed and deployed by NanoX will revolutionize clinical diagnostics and research by providing new ways to directly image, characterise, diagnose, and treat diseases in any species at a level of detail and complexity that was previously unattainable.