A microfluidic platform for automated in vivo studies of bacteria in C. elegans worms: digestion processes and the relation microbiome - worm development
Description: The nematode Caenorhabditis elegans is a versatile model system to address fundamental questions in fields like developmental biology, neurobiology, and aging. In particular, due to genetic resemblance, this millimetre-sized model organism is extremely relevant to human biology, e.g. for the study of neurodegenerative diseases, while it offers genetic amenability and permits low-cost culture conditions compatible with large-scale screening. C. elegans has also been applied to the study of microbial pathogenesis, as virulence factors involved in the killing of C. elegans may also be required for pathogenesis in humans. Another major actual topic in modern biology research is the gut-brain axis, and more specifically the microbiota-gut-brain axis. There is now increasing evidence that gut microbiota influences brain development, function, and mental health indeed. Furthermore, alterations of the gut microbiome might be related to certain human pathologies, such as Alzheimer’s disease. We aim to develop in vivo microfluidic tools and assays to unravel the role bacteria play in the life of C. elegans. Microfluidics allows studying worm populations that are sufficiently large to be statistically relevant, while enabling each worm to be individually tracked throughout its entire lifespan. Bacteria are the worms’ natural food source and alternating feeding with normal and short sequences of fluorescent bacteria will allow studying the dynamics of the digestion process in a worm using fluorescent imaging. As worms in their natural environment develop a proper microbiome in their gut, we will also use C. elegans for in vivo microbiotic studies in relation to worm development. The work will be done in synergy by two PhD students. The first PhD student will realize a microfluidic platform, in which worm populations will be studied at single-animal resolution. In particular, the question on the relation between bacterial digestion and its influence on worm growth and health will be addressed by using microfluidic chips, in which worms will be cultured and imaged during their full lifespan in an automated way. We will investigate how digestion is affected by worm’s environmental and physiological conditions, such as the type and quantity of bacterial food and worm age. The second PhD student will realize a dedicated microfluidic chip for high-resolution microbiome imaging inside the worm gut and study how bacteria affect worm health and development. The chip will enable accurate and reversible immobilization of larvae and worms during restricted periods over their life cycle, resulting in microscopic imaging at single bacterium resolution of gut colonization processes. We will evaluate the effects of exposing worms to probiotic or pathogenic bacteria and we will also do the high-resolution imaging of neurons using fluorescent mutant worms and investigate in vivo if there is a link between neuronal development and the microbiome and/or bacterial exposure of the worm.
Amount: CHF 679,900
Funding type: research
Funder scheme: Project funding
Start date: 2018-05-01
End date: 2023-03-31
Investigator: Gijs, Martin
Institution: EPF Lausanne – EPFL
Subfield: Aging
Domain: Life Sciences
Funded outputs count: 6
Funder award ID: 179021
OpenAlex ID: G4355211427