Mapping tumours in 4D – Spatially and temporally resolved genomics
Tumours don’t exist in isolation. Rather, they are embedded in a living organism and constantly interact with their surroundings. Blood vessels, healthy neighbouring tissues, immune system, and many other local factors all play an important role in the progress of a disease. To study cancer effectively, we must study it in its own context, in situ.
High-throughput sequencing – a method to identify the sequence of most of the DNA and RNA molecules in cells - is incredibly powerful in giving us clues to understand how cells work, but so far it could only be done on a homogenised sample, with a complete loss of spatial information.
In our research group, we are trying to develop a technology to use microscope slides as a support for sequencing, getting information on the genetic content on each cell preserving their position and structure. Furthermore, we are trying to combine this technology with a new type of 3d microscopy and with lineage tracing (a technique to find the “family tree” of a cell) to produce a complete tri-dimensional map of the tissue, and reconstruct how it evolved over time.
Our aim is to be able to obtain a complete molecular fingerprinting of each cell in a tumour (or other healthy tissues), which would reveal many new insights on how the disease progresses and how it could be treated. In my talk, I’ll describe how we plan to get there, and describe some of our preliminary results.