Adult Neurogenesis

Neurogenesis, birth of neurons, occurs most prominently during embryo and early postnatal development to generate the nervous system. However, specific regions of the adult brain retain the potential to produce new neurons that can integrate into existing neural circuits, and in doing so provide functional plasticity to the adult brain. The subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ) lining the walls of the lateral ventricles possess a population of multipotent neural stem/progenitor cells (NSPCs) that support adult neurogenesis. The process of neurogenesis involves initial activation of these quiescent NSPCs followed by multiple rounds of cell division, differentiation, migration and integration. Our laboratory is interested in the effects of genetic ablation on various stages of SGZ neurogenesis, including cell proliferation, apoptosis, differentiation and neuronal maturation, and the fascinating mechanisms that underlie adult SGZ neurogenesis.

Circadian Rhythm

All organisms have biological clocks, which drive and coordinate circadian rhythms in behaviour and physiology according to the demands of a 24-hour world. In mammals, the master biological clock resides in the suprachiasmatic nuclei (SCN) of the hypothalamus. The SCN has endogenous pacemaker activity that runs at near-24-hour cycles and is regulated by the environmental light cycle, thereby allowing the organism to synchronize its internal clock timing mechanism with daily and seasonal variations in the day/night cycle. While genetic studies have established that the circadian clock is comprised of a set of ‘core’ clock proteins that interact in interlocking transcription/translation feedback loops to drive rhythms in their own gene expression, our knowledge of the regulatory processes that feed into this molecular clock remains unclear. Which cascades of cellular events are needed to couple environmental light to the molecular clock? How do individual clock cells synchronize with each other to produce an ensemble rhythm in a tissue? How does aberrant regulation of the circadian clock impact on other biological clocks such as the one controlling cell division? The overall objective of our laboratory is to elucidate the cellular mechanisms that regulate biological timing in mammals, and, in turn, to understand how these cellular mechanisms manifest themselves at the “organism” scale such as animal behaviour, and play a role in diseases arising from their abnormal functioning.