Confocal image of a cerebral organoid showing cell nuclei (yellow), the tangle of neurons (magenta) and astrocytes (cyan) © Diana Brychka & Raphaël Gaudin

ProteoVir project

Fighting neuroinfections by studying the proteins of individual cells in their environment

Impact

Over the past decade, the analysis of living organisms has undergone many improvements, driven in particular by the advent of so-called '-omic' techniques, which provide unbiased overall analysis. For example, such approaches have made it possible to analyse the impact of viral infections on the brain. The aim of the ProteoVir project is to measure the diversity and the amount of proteins contained in each cell individually, while preserving all information related to its environment. In fact, the nature and quantity of cellular proteins are significantly modulated during infection, and successfully identifying such changes with precision means that a protein signature can be associated with each individual cell's response. The technological breakthrough proposed by the project will make it possible to map the perturbations associated with viral infections in extremely fine detail, both in infected cells and in neighbouring cells that are not infected but exposed to a 'sick' cell. These approaches will provide access to an unprecedented level of information which, in the longer term, should make it possible to design therapeutic strategies that specifically target 'abnormal' cells while sparing healthy cells, and which can be applied to infectious diseases and beyond.

Limitations to overcome

Artificial intelligence must enable the automated isolation of cells from tissue. It is also essential to be able to isolate and physically transfer a single cell while preserving the sample. Finally, another major challenge is the statistical analysis of large amounts of proteomics data and its interpretation in a spatial context.

Risks

Currently, the sensitivity of the analysis performed on a mass spectrometry platform does not allow researchers to obtain a number of identified and quantified proteins per cell that preserves the location of each cell in the tissue. It is therefore necessary to develop sufficiently sensitive detection techniques to relate the hundreds or thousands of proteins present in a single cell to its microenvironment. The second step is to increase the throughput of the analysis so that it takes a reasonable amount of time to analyse hundreds of cells in the same tissue.

Innovation potential

This project will provide unrivalled analytical power that is likely to change the way questions in the life sciences are approached. Diseases have traditionally been diagnosed on the basis of often non-specific symptoms, but today's research, dealing with the correlations between pathologies and molecular mechanisms, has led to the development of robust diagnostic tests. In the future, analysing a pathology cell by cell in the cell's environment will reveal the deeper impact of a disorder and allow us to look beyond the 'visible' symptoms. This will make it possible to treat pathologies and ultimately provide personalised medecine for patients.

Project leaders

  • Raphaël Gaudin, CNRS research professor, Institute of Infectiology Research of Montpellier (IRIM - CNRS/University of Montpellier)
  • Myriam Ferro, CEA research professor, Proteomics French Infrastructure (ProFI - CEA/CNRS)
  • Jean-Christophe Olivo-Marin, professor at the Institut Pasteur, Biological Image Analysis Unit (CNRS/Institut Pasteur)