In a new Science paper, members of the Cancer Grand Challenges IMAXT team announce ExSeq – new technology that can create nanoscale-resolution genomic maps of tumour samples by combining the expansion of biological specimens with in situ sequencing.
“In 2015, we announced the invention of expansion microscopy, where you take a specimen and physically make it larger, expanding biomolecules away from each other and enabling nanoscale imaging on a regular microscope,” explains Ed Boyden, co-investigator on the IMAXT team and corresponding author of the study. “We quickly realised that not only does this expansion improve resolution for microscopy, it also makes much more room for chemistry to run within the sample. With ExSeq, we’ve adapted expansion microscopy to work with in situ sequencing and can get incredibly accurate maps and information about gene expression, even in adjacent cells.”
Co-lead author Shahar Alon describes the broad potential of the ExSeq technology. “From the beginning, we knew the ability to explore genomics in the context of the 3D environment would be very powerful. In the first instance this motivated us to investigate brain tissue. The location of RNA molecules within a neuron, for example, is very important as it can affect our ability to learn,” he explains. “But the technique can capture very meaningful information about all sorts of biology, including cancer biology – how neighbouring cells influence each other’s behaviours, identification of very rare cells within a tumour, and so on. It’s incredibly powerful.”
Ed Boyden is a Howard Hughes Medical Institute Investigator and Professor of Biological Engineering and Brain and Cognitive Sciences at MIT. Shahar Alon, former member of the IMAXT team, leads the Spatial Genomics Group at Israel’s Bar-Ilan University.
Keep an eye out for our blog feature on this new technology and how it integrates with rest of the Cancer Grand Challenges IMAXT programme. Read the paper in Science here.