Understanding the epitranscriptomic regulation of development, behaviour, health, and disease
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The epitranscriptomic mark N6-methyladenosine (m6A) is a prevalent and conserved chemical alteration in eukaryotic mRNA which has recently been shown to regulate various processes underlying behaviour, including brain development and plasticity. However, how m6A (e.g., through which molecular pathways, neuronal circuits, and specific genes) regulates behavior remains mostly uncharted. The lab aims to uncover foundational knowledge of how, where, and when m6A acts to regulate a suite of evolutionarily conserved and interconnected behavioral phenotypes with broad implications in health and disease. Within this goal, we focus on:
1. Developing novel approaches to investigating the molecular pathways through which mRNA methylation regulates behavior
2. Understanding the role of m6A in regulating feeding behaviour and metabolic phenotypes
3. Understanding the role of m6A in regulating neurodevelopment, sleep, and learning and memory
4. Understanding the role of m6A in protein homeostasis and longevity
Understanding the molecular basis of pleiotropy
Behavioural phenotypes are complex and typically regulated by many genes and gene-environment interactions. Some genes, however, can have major effects on behaviour. One such example is the foraging (for) gene in Drosophila melanogaster, with a role in regulating several behaviours including feeding, sleep, learning and memory, and sociality. for affects these phenotypes independently, a concept known as pleiotropy. The lab uses naturally-occurring alleles of for, as well as transgenic approaches, to uncover how a single gene can independently regulate distinct phenotypes and modulate behavioural differences between individuals. To answer this question we use behavioural assays, transgenics, genomics, transcriptomics, and molecular biology techniques. Some specific questions we are currently working on are:
1. How do polymorphisms in the regulatory regions of for contribute to its pleiotropic expression patterns?
2. What are the molecular pathways by which for regulates behavioural phenotypes?
3. What role does for play in regulating behavioural differences between individuals, sexes, and in response to the environment?