In situ multiplex tissue analyses to provide biological insights to inform translational research

The advances in high-throughtput sequencing technologies over the past decade have led to substantial progress in our understanding of physiological processes and disease pathogenesis. Their resolution has increased considerably allowing analyses at single cell resolution. Although single cell technologies, such as flow-cytometry or scRNA-seq, enable the detection of multiple biological parameters, they lack the spatial dimension. To unravel the formidable complexities of the tissue microenvironment (TM) at the cell level, scientists must better understand cellular organization in a tissue context. Spatial organization studies reveal cell localization while also providing insights into cell-to-cell communication, signalling patters and how these interactions influence the TM. This integrated information is crucial to shed light on tissue physiology and the disease microenvironment in fundamental and translational studies.

Cambridge offers a multidisciplinary environment of excellence to perform basic and translational research. The Cambridge Biomedical Campus include research institutions like Cambridge Institute for Medical Research, Stem Cell Institute, CRUK Cambridge Institute, MRC Laboratory of Molecular Biology; Pharma companies (e.g. AstraZeneca or Abcam); and Hospitals (Addenbrookes and Royal Papworth). The Early Cancer Institute (ECI) is a new centre at the heart of the Biomedical Campus and the first Institute in UK dedicated to understand the earliest steps of cancer formation and develop strategies to detect, prevent and intercept cancer.

We propose to acquire the Akoya PhenoCycler - Fusion (APCF) system, allowing multiplexed high-dimensional spatial imaging and multiomic phenotyping (transcriptomics/proteomics) at the single cell level, which will be hosted at the ECI. This technology is unavailable in Cambridge and the Biomedical Campus, and would substantially enhance our research capabilities. It will provide a Spatial Phenotyping and Imaging Facility, and we are ideally placed to make this available to nearby facilities, while it will potentiate our visibility in a highly competitive research environment. We have forged a strong collaborators network - our Disease and Cancer Investigation Hub -including researchers working in chronic disorders and cancers with very poor patient outcomes/survival (cancers unmet need): oesophago-gastric cancer (Rebecca Fitzgerald, Lizhe Zhuang), brain tumours (Manav Pathania), NAFLD, cirrhosis and liver cancer (Matthew Hoare; Masashi Narita), lung cancer (Daniel Munoz-Espin) mesothelioma tumours (Stefan Marciniak, Robert Rintoul) and pancreatitis/pancreatic cancer (Giulia Biffi).

Of note, the Disease and Cancer Investigation Hub includes beneficiaries of researchers working at the interplay of the TM with physiological and multiple pathological conditions in our Biomedical Campus, West Cambridge Campus and beyond. APCF system will be available to groups working in - but not restricted to - regenerative medicine and cellular fate (Maria Alcolea), infection and immunity fields (Eoin McKinney), neuroscience, molecular/cell biology areas (Madeline Lancaster, computational biology (Florian Markowetz), or bioengineering (Ljiljana Fruk).

Altogether, the ECI is committed to providing cutting-edge technology and know-how for multiple disciplines across the Cambridge Biomedical Campus, and to creating a facility suitable for the training of technicians, students and postdocs. Since the ECI works extensively with tissues from preclinical models (AMB Animal Facility) as well as with archival clinical samples (Cambridge University and Royal Papworth Hospitals), we are ideally placed to help develop and share the protocols for analysing a range of sample types. Our proposal paves the way for basic biology and more translational biomarker studies including in the setting of clinical trials to unravel the TM and evaluate treatment response and resistance mechanisms.

The advances in high-throughtput sequencing technology over the past decade have led to substantial progress in our understanding of tissue physiology and disease pathogenesis. The resolution of these technologies has increased such that we can now perform analyses down to the single cell resolution. However, the library preparations have until recently meant that the spatial context has been lost. Spatial biology studies enable the transcript co-expression patterns to be ascertained alongside with insights into the organisation, interaction and communication of cells and their interplay with the extracellular matrix across the entire tissue landscape. This paves the way for studies into fundamental biology as well as more translational biomarker studies through to application in the setting of clinical trials to evaluate treatment response and resistance mechanisms.

The Early Cancer Institute (ECI) is a new centre at the heart of the Cambridge Biomedical Campus and the first Institute in UK fully dedicated to understand the earliest steps of cancer formation and develop strategies to detect, prevent and intercept cancer. We propose to acquire the Akoya PhenoCycler - Fusion (APCF) system, allowing multiplexed high-dimensional spatial imaging and multiomic phenotyping at the single cell level, which will be hosted at the ECI. The multi-omics capability combined with its imaging analytical software allows deconvolution of complex cell identities and states, and generate open-source data for computational imaging research. This technology will set foundation for a Spatial Phenotyping and Imaging Facility in a highly competitive research environment. We have forged a strong network of collaborators - our Disease and Cancer Investigation Hub - including researchers working in cancers with very poor patient outcomes and survival rates, and scientists focused on physiological processes and multiple pathological conditions across the whole Cambridge Biomedical Campus.