Spatial Biology in Drug Discovery

Author: Caitlin Smith

Today’s spatial proteomics and transcriptomics platforms allow researchers to probe gene expression in tissue sections with subcellular resolution. Profiling molecular phenotypes while retaining spatial information of expression is not only suggesting new relationships among signaling molecules, but is also deepening our understanding of disease mechanisms. This article looks at advances in spatial biology and how they are helping to advance disease research and drug discoveries.

Spatial transcriptomics and cellular neighborhoods

Like people, cells don’t live in isolation; scientists are learning that cellular neighborhoods are composed of different cell types that influence each other. Vizgen’s recently released MERSCOPE™ platform uses a massively parallel imaging technique called MERFISH (multiplexed error-robust fluorescence in situ hybridization) to measure the copy number and spatial distribution of 500 different genes with subcellular resolution.

Vizgen is working to profile such neighborhoods with Nir Hacohen, Director of the Cell Circuits Program at the Broad Institute of MIT and Harvard, and Director of the Center for Cancer Immunology at Massachusetts General Hospital. “These [neighborhoods] are niches within the tumor microenvironment, groups of cells that are all interacting together to create functional hubs within the colorectal tumor,” says Emanuel. “Being able to profile these tumors and all these interactions at the neighborhood level has a lot of promise, and can help to understand how to perturb them to make the tumor less viable.”

Vizgen also collaborated with Compugen, a company interested in discovering unknown drug targets and expanding use of cancer immunotherapies, to map different cell types and their potential interactions in colorectal tumors. “In particular, they found activated dendritic cells secreting CXCL10 adjacent to CXCR3+ CD8 T cells, suggesting there’s some sort of cell-cell communication happening between these cell types,” says Emanuel. Using spatial profiling to interrogate cell types and signals involved in organized, cellular neighborhoods such as the tumor microenvironment is an approach that is only just beginning to bear fruit.

Vizgen’s platform will soon expand to accept formalin-fixed, paraffin-embedded (FFPE) tissue, a common sample type that can be especially helpful when studying infectious diseases. “With fresh frozen tissues, an infectious agent is still active, so it requires certain biohazard considerations,” says George Emanuel, Scientific Co-founder and Senior Director of Technology and Partnerships at Vizgen. “But if you can use FFPE tissue where everything’s deactivated early on, it makes it much easier to use infectious disease samples.”

Further expansions are on the horizon. Because proteins can mark information distinct from that marked by RNA, Vizgen will also soon add the option of up to 5 custom protein biomarkers along with a gene panel. “Proteins can help to trace some cellular or subcellular morphologies, for example the projections coming out of microglia or astrocytes,” says Emanuel. Protein biomarkers, in addition to increasing the profiling panel from 500 to 1000 genes, will give Vizgen users an even broader range of spatial biology tools.