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A group of researchers led by Dr Roman Fischer at NDM’s Target Discovery Institute, Centre for Medicines Discovery (CMD) and CAMS Oxford Institute Principal Investigator has developed a method to study proteins in human tumours by creating detailed maps that show how much of each protein is present in different parts of the tissue.

Knowing how proteins are arranged in tissues is crucial for understanding their functions and the causes of diseases. To do this, a technology that can accurately map the various proteins in tissues without any biases is required. Such mapping helps to define the molecules' characteristics in the specific tissue structure framework.

In the study, published in Nature Communications, the researchers used this approach on an atypical teratoid-rhabdoid tumour. This is a rare type of brain tumour usually diagnosed in childhood. By studying it at three levels of detail, they uncovered unique protein patterns across the structure of the tumour. The team used spatially-aware algorithms that do not require prior information about the exact tissue structure to map thousands of proteins and pathways across the tissue. The researchers studied how proteins are related to the tissue's differences and cellular features, such as the surroundings or proximity to blood vessels.

They discovered specific markers that helped in pinpointing the boundary of tumours. By examining the protein networks in the extracellular matrix of tumours, they found that the immune response is organized in a spatial manner. Thus, this research provides a new way to study the diversity within tissues at molecular level, helping us better understand the biology and pathology of tissues.

Dr Roman Fischer, Associate Professor and Head of the Discovery Proteomics Facility, at NDM’s Target Discovery Institute said: ‘Our paper shows for the first time the use of systematic spatial protein measurement in a brain tumour. This means, the proteins can be analysed keeping their location in mind. By doing this, we can track areas of increased immune activity and other abnormal processes within the tumour, helping us to understand cancer in much greater detail, for example, why only certain areas of a tumour trigger an attack by the immune system and which proteins we need to target with drugs to support this fight in other areas.’

The research showed that our comprehensive analysis of tumour proteins can reveal patterns related to the availability of nutrients which can affect drug delivery and efficacy. This sets the stage for future studies that combine spatially-resolved transcriptomic and proteomic, which will provide a better understanding of disease processes by using advanced bioinformatics tools.

Read the full paper here: https://www.nature.com/articles/s41467-023-43520-8

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