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Next Generation Imaging

Project description

The next generation of 'next generation' sequencing methods is on the horizon

The sequence of nucleotides in DNA reveals information about genes, chromosomes and even an entire genome. High-throughput 'next generation' sequencing methods have now made it possible to sequence the human genome in a day. Contributing to the meteoric increase in our understanding of genetics and mutations in health and disease, the techniques face an important limitation. EU-funded scientists are addressing it, significantly enhancing the resolution of both spatial localisation and organisation of sequences within single cells in intact tissues. Combined with faster and more detailed analyses and a decrease in cost, the technology could spur a new age of discovery.

Objective

Next generation sequencing has led to revolutionary discoveries in the fields of genetics, genomics, epigenetics and transcriptional regulation. The main limitation of this technology relies on the loss of spatial information: NGS is unable to retrieve the organization of nucleic acids (DNA/RNA) in the cell or within the more complex structure of the tissue. We have recently developed a novel imaging-based technology, Hi-M, that enables the simultaneous detection of tens of DNA and RNA species in single cells within the context of intact tissues. In NGI, we propose to make major improvements to drastically reduce data acquisition and analysis time, considerably increase throughput and number of independent nucleic-acid species detected, and improve the robustness of acquisition and the user-friendliness of analysis. These objectives will be achieved by implementing, testing and validating a novel combinatorial labeling scheme, parallelized acquisition, improvement of the liquid-handling robot to handle hundreds of independent species, and on-the-fly analysis using deep learning technologies to provide more robust data analysis pipelines and adapt acquisition parameters in real time. These improvements will enable simultaneous detection of thousands of species (DNA, RNA or protein) in single-cells with spatial resolution within the context of complex organisms and tissues. Because of these important advantages over existing technologies, NGI will be key to future discoveries in the fields of genetics, genomics and transcription. Critically, NGI will also have a large impact in other fundamental and applied fields where knowledge of spatial organization of transcription and 3D chromosome organization at the single-cell level are relevant: neuroscience and neurological diseases, diabetes, cancer, etc. Thus, NGI has the potential to become an ubiquitous tool not only in academic science but also at the clinic.

Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution
€ 150 000,00
Address
RUE MICHEL ANGE 3
75794 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost
No data

Beneficiaries (1)