Animal development hinges on where and when different genes are expressed. Brian DeVeale is delving deep into the genome to dissect roles that molecules called MicroRNAs (miRNAs) play in gene expression.
Humans have more than 1,000 distinct miRNAs. At least two dozen mammalian miRNAs are essential for viable development, and mutation or excess production of many others disrupt development.
“We know dozens of miRNAs are essential for viability and many others are extremely important for health,” says Dr. DeVeale, an assistant professor of biomedical sciences.
“Yet several distinctive features of miRNA biology have limited our understanding of how each miRNA contributes. We’re trying to determine which targets of individual miRNAs are important for each of their functions.”
The details of where and when most miRNAs are present during development are also fuzzy, which makes it difficult to pinpoint the cellular context in which they are critical.
“We are starting with new assays to improve our mechanistic understanding of how microRNAs work using a single family, but I would like to move onto other miRNAs that are important in a variety of clinical contexts,” he says. “For example, dysregulation of one particular miRNA is either associated with schizophrenia or autism depending on the nature of its dysregulation.”
Before expanding into situations where there is a clinical feature of interest, DeVeale will start by focusing on a specific family of miRNA that accelerates cellular division rate.
“Animal development requires that cellular diversification occur at precisely the right time and place in embryos and miRNAs are critical to this diversification, its precision, and robustness, including to environmental stress,” says DeVeale.
“Unlike most genes, miRNAs do not function by producing proteins, instead they act by destabilizing or suppressing translation of protein encoding RNA networks.”
The initial screen will look at cellular division rate of cells. The long-term objective of his research program is to understand how miRNAs contribute to the production and function of different cell types in development.
In addition to a Natural Sciences and Engineering Research Council (NSERC) 2023 Discovery Grant of $33,000 for his lab’s research into miRNAs, DeVeale received an Early Career Researcher award — for faculty in the first five years of academic appointments — of $12,500. He started at UWindsor in January 2023.
“This is a unique screen with lots of discovery potential,” DeVeale says, “so I’m excited to execute it and then chase offshoots.”