Spatial Biology Multiomics: BioChain’s Investment in the Future Pt. 1
A Conversation with Dr. Rikita Gakhar, Ph.D. Application Scientist, BioChain Institute Inc. and Dr. Vidya Sundaram, VP of Business Development
The Birth of Spatial Biology
Q: What do we mean when we use the phrases “spatial biology” and “spatial multiomics”?
A: Rikita: “Spatial multiomics can be broken down into three aspects - there is Spatial, Multi, and then the “Omics' ' aspect. In the early 2000s, the development of next-generation sequencing technologies created a buzz in the world of molecular biology. Fairly soon after that, everyone had access to sequencing and a multitude of data was being generated giving rise to omics for DNA and RNA studies. Scientists were using bulk RNA sequencing to study structure and function in the microenvironment of plants, animals, and their associated microbiomes and called it transcript-omics.
Bulk sequencing gave us an idea of what genes were being expressed but then the question was which cells are expressing those genes. We could not trace back the gene expression to individual cells in the tissue because the RNA was derived from pulverized tissue.
Single-cell RNA sequencing was developed to address that and study individual cells. Now we could tag individual cells and sequence RNA. It became a popular genomics tool to get all of the transcripts from individual cells within a tissue. But the tissue still had to be dissociated and the question became where are these cells located in the tissue.
Biology is complex and dynamic, cells in a tissue undergo various cell-to-cell interactions and evolve together with diverse cell types - whether it is developmental biology or disease pathology and immune response. These complex interactions take place both spatially and temporarily in microenvironments of a tissue. That is what makes it important for us to study these tissues in spatial context so we can get a real-world picture of what is happening in these micro-neighborhoods.
To understand how individual cells interact with their specific neighbors and what that neighbor does further in disease development or whatever biological aspect we are studying.
To take it a notch further we can look at the changes not only at the level of RNA but protein as well as metabolome —hence the term “multiomics.””
Vidya: “To put it simply, spatial multiomics allows us to build a Google map of tissues where individual cells are like houses and there are different neighborhoods. We are trying to figure out the neighborhoods that are important to disease development and the role they play in predicting a patient’s response to therapy.”
Understanding Spatial Cell Context and Applications
Q: How did this need translate into the work being done in research laboratories?
A: Rikita: “Think about a tissue — a single blob of cells. There are multiple cell types and cell states in there, and they’re communicating with each other with the help of these molecules. These communications are dynamic but also specific in determining the function of the tissue as a whole. So to study that, instead of breaking up the tissue, which we needed to do for single-cell and bulk RNA sequencing, scientists want to keep the tissue intact. This way they can see and compare the neighborhoods and identify which particular communication is responsible for normal development and the deviations that lead to disease development.
Vidya: In oncology specifically, we call them tumor microenvironments consisting of not only tumor cells but the infiltrating immune cells as well. They’re all communicating with each other spatially.
Rikita: That is how spatial biology came into development. It combines histology, the tissue morphology, with the molecular biology world. Up until the development of spatial biology, pathologists were studying the histology of the tissue, and molecular biologists were studying gene expression. And now, scientists can combine these two disciplines and study diseases in the entirety of tissue sections.”
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