Neurobiology of vertebrate reproduction: the granin-derived neuropeptide secretoneurin is a new reproductive hormone

点击翻译按钮获取中文摘要

Acquiring new knowledge about hormones that control animal reproduction is the main goal of my research. Environmental signals such as light and temperature can regulate reproduction by changing the activities of genes that themselves are responsible for hormone production in the body. My laboratory made the compelling discovery of a new sex hormone called secretoneurin. In fish there are 2 forms of this hormone, which we named secretoneurin a and secretoneurin b. They are the short peptides resulting from specific degradation of larger protein products of the secretogranin-2a and 2b genes. Using the CRISPR/Cas9 gene editing technology, we created zebrafish with one or both secretogranin-2 genes deleted. These unique models will allow my group to determine the functions of this novel hormone system. The sexual behaviour of these fish will be studied and compared to normal animals. Experiments with isolated tissues and injections of synthetic version of secretoneurin will lead us to determine how and when secretoneurin stimulates reproduction by examining effects on the brain, pituitary gland, ovaries and testes. We will study transgenic fish whose neurons and pituitary cells are marked with fluorescent proteins. This will lead to the discovery of how they communicate with other cells. A new method called single cell RNA sequencing will be employed to fully characterize and classify the cell types producing secretoneurin. A major challenge we will undertake is the identification the secretoneurin receptor. We would then determine the role of the receptor in reproduction, driving our research to the next level. The structure of secretoneurin is very similar between different vertebrate animals. The knowledge gained from research on fish may help us understand reproduction control mechanisms in other animals, for example in frogs or humans. On a more practical scale, the expected results may have applications for controlled reproduction in aquaculture. Importantly, young scientists will receive training in state-of-the art techniques in a dynamic and inclusive research environment. They will use genome editing techniques for fish, RNA sequencing and bioinformatics, and proteomics (a high-powered method to measure hundreds of proteins at one time). These highly qualified personnel will be encouraged to present at national and international conferences, mentored on career development and will publish their results in scientific journals. They will be highly sought after by academia, industry, or government research departments.