In the lab, we take an integrative and comparative approach to study glial-neuronal interactions in relation to early development, physical injury, and neurological disease that spans across multiple levels of biological organization (molecular and cellular physiology > systems biology) and multiple model species (zebrafish, rodent and human). Our work falls under two main themes outlined below.
01
Investigation of glial-mediated mechanisms underlying development and disease
Astrocytes are intimately associated with neurons at sites of newly forming and mature synapses (tripartite synapse), and the interactions between these cell types are integral to regulating development (growth, migration, synapse formation) and maintaining homeostatic functions (ion balance, excitability, survival). In particular, we focus on astrocytic regulation of purine and pyrimidine signalling, and the physiological consequences related to changes in the gliotransmission in Fragile X Syndrome (FXS). Notably, perturbations in ATP/UTP signalling significantly impacts glial physiology and highly contributes to the abnormal neural circuitry associated with FXS, the leading genetic cause of Intellectual Disability and Autism Spectrum Disorders. We are exploring these novel cellular and molecular relationships in FXS and in astrocyte-mediated regulation of brain development, including neurogenesis, synaptogenesis, metabolic homeostasis and oxidative stress.
02
Exploration of naturally adaptive models with significant recovery from, or tolerance to, neurological stress or disease
We are also applying these approaches to the study of stress responses within the CNS. We are interested in the adaptive strategies of stress-tolerant animal models and natural ‘regenerators’. The use of zebrafish as a model species provides a great opportunity to study highly adaptive forms of neuroplasticity, particularly those involved in neuroprotection and regeneration. Ongoing work has found interesting differences in purinergic signalling, evolutionary conserved in fish, using established protocols to examine radial glial interactions that underlie injury-induced CNS neurogenesis in zebrafish.