Should I stay, or should I go? How brain stem cells decide to leave quiescence

Multiple projects available to suit Honours or PhD students

Quiescence is a type of reversible cell-cycle arrest displayed by many resident tissue stem cell populations, which helps to ensure we have a lifelong population of stem cells to maintain tissue homeostasis, respond to injury and other stimuli. One region where these stem cells exist is in the brain. In mice, a major model organism, there are two main stem cell niches in the adult brain. These are the subgranular zone of the hippocampus and the subventricular zone lining the lateral ventricles of the forebrain. When quiescent neural stem cells in these regions activate, they generate neurons that function in memory, spatial navigation and odour discrimination. Similar neural stem cell populations with similar functions exist in the human brain.

AIM

This project aims to uncover novel molecular regulators of brain stem cell quiescence. One prism through which this will be explored, is by interrogating how brain stem cells enter deeper quiescence during the aging process. The project will employ a range of techniques using aged wildtype mice, genetically modified mice and primary neural stem cell cultures derived from the hippocampus and subventricular zone of postnatal/adult mice. The outcomes of this project are expected to shed light on how quiescence is regulated. The genes/cellular processes we identify as being important in quiescence can then be explored in the context of diseases where adult neurogenesis is disrupted, for example during aging and major depressive disorder. Likewise, these findings will also be of interest to brain cancer research, where quiescence is frequently co-opted by cancer stem cells to evade therapies.

Specifically, this project will:

1) Establish the role of a novel group of calcium-binding proteins in deciphering activation/proliferation cues using in vitro and in vivo models.

2) Determine if decreased expression of these proteins explains why quiescence deepens during aging.

3) Determine if these proteins are functionally important in the progression of brain cancers, with a specific focus on quiescence and treatment resistance.