Using gene-editing technology, the team was able to cause mutations in genes that encode for a large protein called secretogranin-2. This protein was already known to be processed to smaller bioactive fragments called peptides. Prof. Trudeau and his team showed that one specific peptide called secretoneurin actually stimulates reproductive processes in the zebrafish, a model organism for biological and medical research.
The road to this exciting discovery began when Prof. Trudeau’s laboratory identified the secretogranin-2 gene and secretoneurin peptide in goldfish some years ago. However, in vivo evidence was critically missing, meaning that his team needed to demonstrate a vital role of the natural gene in a living organism. Fortunately, gene-editing methods were concurrently being developed for fish and Professor Wei Hu, a researcher at the Chinese Academy of Sciences (CAS), who has considerable expertise in gene-editing, had a short sabbatical visit to Ottawa already back in 2011. Thus, Professors Trudeau and Hu began their friendship and collaboration, leading to the development of the very first secretogranin-2 mutant model.
Prof. Trudeau’s PhD students took the lead and helped further advance secretoneurin research. Among them is a former student, Dr. Kimberly Mitchell, who studied the disrupted sexual behaviour in the mutant fish and spent some time in Dr. Hu’s lab in Wuhan, China. The Ottawa and Wuhan laboratories have very complementary expertise, which has led to this fruitful collaboration and joint research grants.
Ultimately, they discovered that secretoneurin is a reproductive peptide and is indeed a new sex hormone. Prof. Trudeau’s team showed that secretoneurin can stimulate the brain and pituitary gland to release other well-known hormones that themselves have key roles in reproduction. These are completely new findings, opening up a new area of investigation for researchers interested in the factors that control sexual behaviour and fertility. In addition, they found secretoneurin to be conserved over the course of evolution, meaning that what Prof. Trudeau and his team discovered in fish could potentially have much broader applications in other species, including humans. Uncovering a reproductive role for secretoneurin could lead to new ways of controlling reproduction in cultured fish species, or help with the search for new infertility treatments in humans. With other hard-working PhD students currently pursuing this research, Prof. Trudeau is hopeful for what is to come, stating, “There is a very good chance that we will find other novel peptides with new biological roles.”
