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Cellular mechanisms | Cognition | Molecular mechanisms

“Understanding the processes of pathogenesis” Program

Published on 15 January 2015
Imaging, structural biology, large-scale biology, high-throughput screening, and preclinical models are all skills and tools of the Life Sciences Division (Direction des sciences du vivant - DSV) for use in the multi-scale study (i.e. molecule, cell, organ, and organism) of normal and pathological biological phenomena. Teams from the DSV are accordingly devoted to working on cancer and infectious, neurodegenerative, or genetic diseases.

More knowledge for health innovation

Researchers at the DSV are expanding the fundamental knowledge of cellular architecture, organization, regulation, and their interactions with the exterior environment. They also explore the biochemical reactions regulating cell functions (e.g. energy production, manufacture and transport of molecules, damage repair, and waste elimination). All of this information helps to understand how certain physiological processes shift from normal to pathological, in addition to identifying novel therapeutic, diagnostic or methodological leads (see box).

This research forms the basis of the CEA’s innovation in the fields of radiation biology, therapy and diagnosis. The focus is on three areas:

  • Understanding the mechanisms of genome plasticity, integrity and expression
  • Studying the human genome
  • Understanding normal and pathological molecular and cellular mechanisms

Observation by fluorescence microscopy of the protein Arpin (green) and actin fibers (red). An international collaboration involving the CEA-IBITECS and the CEA-IRTSV led to the discovery of the protein Arpin and its role in the regulation of cell migration, a phenomenon closely linked to the formation of metastases. These results should have a significant impact on research against cancer. © CEA

The mechanisms of life as a source of high-performance tools

In the early 2000s, scientists discovered RNA interference. This phenomenon explains the existence of small RNAs in cells that do not encode any protein (siRNA, miRNA) and their function in modulating gene expression. Researchers were inspired by this to create small artificial RNAs, which are now essential laboratory tools for “turning off” genes in a simple and targeted manner. At the CEA, researchers are very interested in making these even more effective by conceiving of large-scale developments: the screening of all genes expressed in a cell to understand their function; creating stable cellular models of disease and identifying therapeutic targets; and designing highly targeted therapies.

National Infrastructures in Biology and Health in the service of fundamental research

The DSV coordinates several National Infrastructures in Biology and Health, created with financing from the “Investissements d’Avenir” program. Some services proposed by these infrastructures are even utilized within the DSV to better understand the molecular and cellular mechanisms of living organisms:
  • ProFi (Proteomics French Infrastructure), for the detailed analysis of the dynamics of multiprotein complexes involved in different signaling pathways
  • FRISBI (French Infrastructure for Integrated Structural Biology), for structural biology
  • France Génomique, for genomics

A multi-scale, multidisciplinary research

Researchers at the DSV implement a multi-scale approach to study living organisms, using specific skills at their disposal:

  • Integrated structural biology and imagery allow passing from the molecular to the organismal level, by reconstructing 3D structures of macromolecules and the dynamic arrangement of cellular machineries
  • The “omics” disciplines  (e.g. genomics, transcriptomics, and metabolomics) are implemented to gather information on the quantitative and qualitative variations in cell components during a normal or pathological event
Dividing stem cells give progenitor cells, which move throughout an organ and produce differentiated cells. Here, researchers are studying in vitro the behavior of progenitor cells of the brain (e.g. neurons, astrocytes, and glial cells) following irradiation.
© F Boussin/L Gautier/CEA

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