Project

eGRIDE - Evolutionary mechanisms of gene regulation in dynamic environments

Living Systems are the product of évolution in a dynamically changing world; they endlessly adapt to new challenges imposed by their environment. Yet, our understanding of evolutionary mechanisms involved in adaptation to dynamic environments is very sparse. Even though gene régulation is well-known to endow cells with the ability to adjust their phenotype according to environmental fluctuations, we know little about genetic changes that fuel regulatory évolution or about the benefits and costs of regulatory changes. This lack of knowledge impacts several fields in biology: from the biomédical challenge of cancer plasticity where evolved gene régulations allow cancer cells to escape treatment, to the challenge of synthetic biology where gene circuits must be controlled despite environmental fluctuations.

This project builds on genomic advances to détermine how the évolution of gene régulation dépends on 1) mutational effects - “what can happen?”, and 2) the sélective advantage of regulatory changes in dynamic environments - “who can survive?”. These fundamental questions will be addressed at the transcriptomic scale by combining innovative experimental and computational approaches in a powerful model organism: the yeast Saccharomyces cerevisiae.

Using a novel high-throughput method by which the transcriptomes of thousands of genotypes can be profiled in different environments, we will détermine how random mutations potentiate or constrain regulatory évolution and we will identify genetic variants altering gene régulation. By competing random mutants and performing functional assays under diverse régimes of sélection, we will détermine when and for which genes the évolution of expression régulation is bénéficiai.
This work will advance our understanding of the genetic mechanisms underlying regulatory différences and of their adaptive value in dynamic environments, providing an empirical foundation for the development of prédictive models of regulatory évolution.

"eGRIDE Rubix". Stereomicroscope photos of encapsulated yeast cells taken by Nena MARTIN, 3D design by Fabien Duveau. 2024

An imagery cube symbolizing the multidimensional aspect of data needed to understand how interactions between genotypes and environments influence the regulation of gene expression. Each image represents a micro-colony of yeast cells (dark aggregates) encapsulated in an alginate bead; the colors represent different environments. The eGRIDE project involves the quantitative transcriptome analysis of ~1000 genotypes in ~7 environments from encapsulated cells.

EU contribution: 1,961,573€

Duration: form September 1st, 2024 to August 8, 2029