The Head of Electron Microscopy helps us understand why Volume Electron Microscopy was named Nature’s Technique of the Year

GIMM: Nature has distinguished Volume Electron Microscopy as “Technique of the Year”. What does this choice actually mean?

ANA LAURA VINAGRE: Nature’s distinction recognises a set of techniques that make it possible to study biological samples in three dimensions, with nanometre-scale resolution, across very large volumes. This is not a new technique, but rather a field that has now reached a level of technological maturity that allows an unprecedented amount of information to be extracted. In particular, connectomics – the complete mapping of connections between neurons – was central to this choice.

GIMM: What are volume techniques in electron microscopy, after all?

ALV: Traditionally, electron microscopy provides two-dimensional images – essentially a “photograph” of a very thin section of a sample. Volume techniques go further: they allow an object to be reconstructed in three dimensions from multiple sections or successive acquisitions. Instead of seeing just a single XY plane, we can follow an entire structure, such as a neuron, throughout its full volume.

GIMM: What are the main achievements in this field?

ALV: Recent projects include the complete reconstruction of the brain of an adult Drosophila, as well as one cubic millimetre of a mouse brain, both at electron microscopy resolution. These are large-scale projects involving international consortia, multiple research groups and even companies. Dedicated microscopes had to be developed, new workflows created, and absolutely massive data volumes managed. Connectomics is not just the final image: it involves sample processing, data acquisition, segmentation and computational reconstruction.

GIMM: What does GIMM’s Electron Microscopy platform already do in this area?

ALV: At GIMM, we already carry out volume techniques such as electron tomography, which allow us to reconstruct very small volumes, on the order of nanometres. One example is projects involving microalgae, where it is essential to understand the three-dimensional structure of organelles such as the centriole. Depending on the orientation of the section, a 2D image can be misleading. Only volume reconstruction allows us to understand the true geometry of the structure. The same applies to cells infected by parasites, such as red blood cells infected with Plasmodium. Reconstructing the entire cell makes it possible to locate and characterise the parasite much more precisely.

GIMM: And what distinguishes these techniques from the large-scale volume

ALV: Scale. While we currently work with relatively small volumes, the most advanced techniques allow the reconstruction of much larger volumes — up to cubic millimetres of tissue, such as in the mouse brain. That is precisely the direction in which we want to evolve at GIMM. Whenever three-dimensional organisation is relevant, these approaches make a decisive difference.

GIMM: GIMM electron microscopy service is open to both internal and external researchers. What is the proportion?

ALV: It is 50/50. We work with researchers from other institutes, with clinical samples, and also with industry, including pharmaceutical companies, for example, in quality control contexts. This proportion has remained quite stable over recent years.