Gene expression at a specific time and place is essential for embryo development. Albert Tsai's challenge is to understand how cell nucleus organization promotes the meeting of factors involved in gene expression and ensures the perfect execution of the developmental program.

A timed genetic program for flawless development

In order to avoid embryo malformations, or death in the most extreme cases, genes controlling development must be activated at the right place and at the right time. This delicate mechanism involves the action of proteins inside the nucleus called transcription factors. These factors interact briefly (a few seconds) with particular sequences in the DNA close to the genes to decide whether a gene should be turned on or off. The spatial and temporal distribution and action of transcription factors in the nucleus is of special interest to Albert Tsai, who wants to elucidate how this complexity ensures the smooth development of an entire organism.

A well-organized nucleus

One of the strategies that makes it possible to sort the complexity of gene regulation during development is the organization of the nucleus into microenvironments. These microenvironments bring together transcription factors and their target DNA regions to facilitate their interaction. However, this organization remains poorly understood: what are the physical properties of these microenvironments? How are their location and composition determined? When and how do these microenvironments form during development? Albert Tsai's team will answer these questions using the fruit fly as a model.

Drosophila, a perfect model

The ATIP-Avenir grant will enable Albert Tsai to set up his research team in Montpellier. His team will monitor the various components of microenvironments during development by combining the advanced genetic tools available in the fruit fly, high-resolution optical microscopy and statistical physics. These techniques will allow Albert Tsai and his team to characterize the important ingredients of microenvironments formation, to understand when and how they are formed, and their impact on gene expression leading to the development of an organism. Understanding the sources and limitations of the mechanisms that contribute to successful embryonic development will lead to a better understanding of developmental diseases.

Albert Tsai in a few words

After studying physics and molecular biology at the University of California San Diego and completing his PhD in applied physics at Stanford in 2014, Albert Tsai specialized in imaging interactions inside the cell regulating gene expression. Thus, during his post-doctoral stay at the Janelia Research Campus of the Howard Hughes Medical Institute (USA) and EMBL Heidelberg (Germany), he developed sophisticated genetic and imaging methods to track transcription factors at the single-molecule level. The fruit fly, his favorite study model, will follow him to Montpellier where he will set up his own research team in 2023 thanks to the ATIP-Avenir program. Within the Centre de recherche en Biologie cellulaire de Montpellier (CRBM), he will benefit from a great scientific environment to develop both his career as an independent researcher and his ambitious research program.

ATIP-Avenir Program

Since 2005, the Fondation Bettencourt Schueller has been a partner of the Inserm Avenir program. In 2009, the Avenir program merged with the ATIP program by the CNRS (National Center for Scientific Reasearch). The Foundation has since supported the ATIP-Avenir program which promotes the return or settlement in France of very high-level young researchers, with a research project of exceptional quality, and wishing to create their own team.

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