Spatial omics: Understanding life in 3D
Recent advances in the life sciences have given researchers increasingly detailed insights into the molecular mechanisms underlying health and disease. One thing, however, is missing: the spatial dimension. Spatial omics seeks to remedy this and VIB has invested in this suite of technologies since it burst on the scene. But what is spatial omics, and what are the challenges that remain?
April 29, 2024
Leaving Flatland
Bodies are made of tissues, tissues are made of cells, and those cells are territories bustling with the activity of many, many molecules. To understand the molecular activity in those cellular territories, we need to make maps. But how do we make maps of something we can’t see?
We zoom in.
Even the ancient Greeks already used water-filled spheres to achieve a magnified view of their topic of interest. Throughout the thirteenth to the seventeenth century, advances in glass lenses led to the design of simple microscopes. The true breakthrough, however, came halfway through the seventeenth century, with the advent of light microscopes that allowed scientists such as Antonie van Leeuwenhoek and Robert Hooke to see life, 300 times magnified.
Since then, light microscopes improved significantly and other types of microscopy, like electron and fluorescence microscopes, have literally given researchers a different view of life. But, those views tend to be flat. We flatten cells onto microscope slides or separate cells from their environment to peek at them in detail. This is not only the case for microscopy. Like Edwin A. Abbott’s famous 1884 novella Flatland, which details a two-dimensional world, many analysis methods in the life sciences tend to reduce the complexity of their samples to make the analysis manageable. That hidden complexity, though, might hide a lot of interesting knowledge.
Adding the spatial dimension
That is where spatial omics comes into play.
Rapid advances in single-cell technologies resulted in an unprecedented ability to untangle what truly happens at the level of individual cells. Various so-called omics disciplines greatly increase our ability to draw the maps of the molecular activity that makes life, well, life. Transcriptomics gives us a view of gene activity, proteomics tells us which ensemble of proteins keeps everything running, metabolomics provides insight into all the metabolic processes that churn in the background, and so on.
Spatial omics does all that, with one crucial extra feature: location.
Where a cell resides in a tissue, its 3D coordinates, is critical in shaping its activity and its response to internal and external stimuli. Spatial omics is the discipline that investigates how to add that extra layer of information on top of the traditional omics fields – it gives us a map with coordinates and contour lines.
Since the advent of spatial omics a little over five years ago, VIB has continued to invest in the technology. VIB’s Tech Watch team kept a close eye on developments in the field and has enabled VIB researchers to use the latest advances for their work.
“By adding that extra layer of spatial information,” says Wai Long Tam, Head of VIB Tech Watch and member of the organizing committee for VIB's Spatial Omics conference, “we’ve learned a lot about the importance of a cell’s place within a tissue of interest, especially in the context of health and disease.”
VIB research in spatial omics has already revealed how localized responses to plaques play a role in Alzheimer’s disease, how specific cell types represent a crucial difference between lean and fatty livers as well as how gene activity differences shape the liver. VIB researchers also pioneered spatial approaches in plant roots, the potential of spatial metabolomics in cancer treatment, and even developed analytical tools to help other researchers make sense of complex spatial data.
That last one - making sense of the data - is particularly characteristic of a burgeoning discipline, which is also one of its main challenges: there are not yet many standardized approaches for either sample preparation or data analysis.
Tools and training
“As with any young discipline,” says Wai Long Tam, “there are several hurdles that remain. Because we are dealing with multiple cell types in a sample, the lysis – breaking the cells to reveal their contents – doesn’t happen equally fast, which makes sample preparation challenging, especially because the spatial location of the cells is something we’re interested in. That cellular heterogeneity is also challenging in terms of data analysis.”
But the VIB community is nothing if not driven by curiosity and the desire to push science forward. VIB Technology Training organizes a course with the telling title ‘How to start with spatial omics?’
Alexander Botzki, Head of VIB Technology Training, explains: “That introductory course serves mostly as a quick start, and, importantly, to share experiences among researchers who want to integrate spatial omics in their work. The field as a whole is still searching for proper standardization, which means that people can really benefit from hearing from each other how they all encounter and solve problems along the way.”
VIB scientists are also taking the lead in developing data analysis methods that can help researchers across the globe tackle the spatial complexity in their dataset, whether it’s through organizing hackathons or contributing to workshops by ELIXIR, an organization that unites life sciences institutes across Europe.
Even more, VIB has combined all the spatial omics know-how in the Spatial Catalyst, which offers unique expertise in the field – stay tuned for the next blog post, in which we will learn more about it.
On old maps, unexplored territories were marked by ‘here be dragons’. Spatial omics lets us shine a light on some of those areas on our cellular maps.
Dragons or not, let’s see what we find.
Between 13 and 14 June, VIB organizes the Spatial Omics conference in the beautiful city of Ghent, which will bring together experts from academia and industry to present their most recent discoveries.
