3.7 Optogenetics investigation of microbiota influence on brain development and epigenetics

Principal Investigators

Paul De Koninck, Sylvain Moineau

Co-Investigators

Daniel Côté, Alexander Culley, Nicolas Derome, Arnaud Droit, Marie-Éve Paquet, Grant Vandenberg

Collaborators outside U. Laval

Robert Campbell (University of Alberta), Patrice Couture (INRS)

Project summary

The intestinal microorganisms hosted by humans and other vertebrates play a central role in maintaining their hosts in healthy conditions. However, when the host encounters a physiological stress, the microbiota ecosystem equilibrium is broken, allowing opportunistic microbial strains to induce negative effects on the host, including infections and physiological disturbances. During host development, a stressed microbiota might induce significant consequences on its brain development and neural functions, affecting mental health. The Northern ecosystem is undergoing unprecedented assaults from human activities, leading to dramatic environmental changes that are modifying host-microbiota interactions. The relationships between these complex systems are poorly understood. To learn more about host-microbiota interactions and their impact on mental health, we must develop models and tools with which we can accurately control the variables, relevant to the environment, in a laboratory setting.

Our objective is to develop a fish experimental model in which we can control factors that modulate host-microbiota functional interactions and measure the impact on microbiota evolution, on brain function, and on host gene expression. Our specific aims are to

i) develop molecular tools to study and control microbiota metabolism and growth with optogenetics;

ii) develop multispectral optical imaging of the co-evolution of bacterial strains;

iii) investigate the impact of nutrition, xenobiotics, phages and bacterial strains on the gut microbiota, on neuronal development and brain circuit function and on epigenetics.

The proposed project will involve a transdisciplinary approach combining physiology, optogenetics control and monitoring of gut microbiota, optogenetics monitoring of neural function, as well as genomics and transcriptomics analyses of horizontal gene transfer in bacterial strains, and epigenetics analyses on developing host. The project will lay the foundation of an experimental setting in which several variables critically important to Northern ecosystems will be investigated.