Regulation of Adult Neurogenesis by Autophagy

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My NSERC funded research program is tackling the question of what regulates how adult stem cells in the adult brain generate neurons. In comparison to the vast amount of knowledge about how neurons develop during the formation of the brain, we have only begun to understand how this process occurs within the adult brain due to scientific advances that have discovered how to isolate and manipulate individual cells within the mature brain. This is important to understand since it is imperative to have fundamental knowledge on how neurons are generated in the adult brain in order to promote and sustain the development of neurons while aiming to improve brain function. The studies proposed in this grant arise from our lab's discovery that a process called autophagy is essential for the generation of adult-born neurons. Autophagy is often called the cellular equivalent of housecleaning, allowing for the removal of cellular waste and recycling of materials, and thus serves as an important intracellular quality control function. Our findings have led us to question which component of adult neuron development does autophagy effects. Is it required in the stem cells that give rise to neurons? Does it alter the ability of the new cells to divide? Does it affect surrounding cells that provide essential support to the adult-generated cells? To provide answers to these questions we have created novel mouse models that have allowed us to remove an essential autophagy related gene called Atg5 in order to examine how loss of autophagy alters the different stages of development of adult neurons. Included in our experiments is the use of recent technical advances allowing for analysis of the genetic code within individual cells at different stages of development. This unprecedented level of analysis will lead to novel insights in each stage of cell development to identify the mechanisms underlying the ability of autophagy to regulate the generation of adult neurons. This research provides fundamental insights into both adult neurogenesis and autophagy. These studies provide an integrated, multi-level analysis that links the different main players involved in autophagy to the regulation of the different stages of adult neurogenesis, as well as changes in gene expression during this process. The studies are being led by a diverse group of trainees within the laboratory receiving training that is cutting-edge, collaborative, and spans many disciplines. This will allow the trainees to achieve their independent career development goals and give them the necessary uniqueness that will make them valuable, specialized and versatile experts. Importantly for Canada, these students will become the next-generation of leaders in academia and education, as well as in the rapidly growing biotechnology and stem cell industry.