126 Development meets Metabolism: Investigating how Diet and Nutrition Influence Developmental Decisions

Faculty Mentor: Michael Werner (Biological Science, University of Utah)

The effect of the environment on development is critical to human health, and animal and plant ecological strategies. However, the molecular mechanisms that regulate developmental (phenotypic) plasticity remain poorly understood. When exposed to different environments, the nematode Pristionchus pacificus expresses one of two possible mouth forms: either the ‘Stenostomatous’ morph with a narrow buccal cavity and one tooth-like denticle, or the ‘Eurystomatous’ morph that has a wide buccal cavity and two teeth-like denticles. While there has been research tracing the mechanisms behind this phenomenon — histone modifications as epigenetic marks — little is known how dietary conditions during development connect to these mechanisms.

My research aims to assess whether morph choice, an experimentally tractable example of developmental plasticity, is mediated by nutrition and connect it to underlying epigenetic modification mechanisms. Specifically, I initially performed two experiments to test the putative connection between nutritional status and phenotype: 1) grew and collected P. pacificus on different environments – poor and rich nutrition – for metabolomic analysis and

2) conducted dietary restriction experiments with different Pristionchus species to assess the generality and conservation of the diet:phenotype connection. For the primary project, I initiated the growth of ten worm-pellets collected from each NGM agar and liquid culture dietary conditions, that result in differing phenotypic expression, and submitted samples to the University of Utah Metabolomics Core Facility. In the second project, I phenotyped four different species grown on high- or low-bacterial food conditions. Results from the first experiment LC/GC- Mass Spectrometry metabolomics reveal that there are significant metabolite differences between conditions, specifically those related to the lipid and protein metabolic pathways. Results from the second experiment show that all four species exhibited significant differences in mouth form under dietary restrictive conditions. Collectively, these results suggest that the effect of diet on morph choice is a deeply rooted phenomenon feasibly connected to lipid catabolism. I conducted preliminary free fatty acid assay and lipid staining in-vivo to quantify the potential lipid differences observed between dietary conditions. Current experimentation focuses on targeting genes asic-2 and gst-9 found to be expressed differentially in P. pacificus from these conditions and relating to metabolism by using CRISPR-Cas9 to mutate in the gene and analyze resulting mouth form effects.