MOLECULAR BIOLOGY LABORATORY OF EPHE
Our research is focused on two highly debated and challenging concepts and their application in gene therapy: the role of epigenetic mechanisms in cell differentiation and the stochasticity of gene expression. Both concepts raise a number of questions regarding their impact on cell differentiation.
Epigenetic mechanisms play a double role. They represent an interface between the environment of the cell and the genome by conveying global regulatory signals through metabolic changes that induce gene expression fluctuations and at the same time ensure the non-genetic transmission of gene expression states over cell generations.
The concept of probability in molecular biology calls into question the postulate of deterministic gene regulation. The growing awareness of stochastic gene expression raises important questions about its implications not only for biological theories but also for practical applications such as gene therapy traditionally founded on perfectly deterministic postulates. Epigenetic mechanisms have been shown to be a major source of gene expression fluctuations.
Our lab is investigating (i) how the clonal stability of cell phenotypes and the underlying stability of gene expression levels can be reconciled with the stochastic fluctuations within the cells
and in its microenvironment; (ii) how cell fate decisions are taken in spite of the fluctuations; (iii) how the experimental manipulations such as transduction using lentiviral vectors generate
epigenetic changes in the host cell genome.
G. Corre, D. Stockholm, O. Arnaud, G. Kaneko, J. Vinuelas, Y. Yamagata, T. M. Neildez-Nguyen, J. J. Kupiec, G. Beslon, O. Gandrillon, and A. Paldi. Stochastic fluctuations and distributed control of gene expression impact cellular memory. PLoS ONE, 9(12):e115574, 2014. [PubMed:25531401]
T. M. Neildez-Nguyen, J. Bigot, S. Da Rocha, G. Corre, F. Boisgerault, A. Paldi, and A. Galy. Hypoxic culture conditions enhance the generation of regulatory T cells. Immunology, Sep 2014. [PubMed:25243909]
Paldi, A. (2013). Effects of the in vitro manipulation of stem cells: epigenetic mechanisms as mediators of induced metabolic fluctuations. Epigenomics, 5(4), 429-437.[PubMed:23895655]