Beatrix Wang

Supervisor: Anastassia Voronova

Project: Molecular mechanisms of white matter formation in the developing brain

Degree program:

Medicine & Dentistry-Medical Genetics

Lay abstract:

The brain is an extraordinarily complex organ, and the process by which it is constructed during development is an extremely complicated one that is still not completely understood. What is known, however, is that neural stem cells (NSCs) are the primary building blocks of the brain, and that they must very carefully differentiate into the right cell types in the right places and at the right times during brain development. Disruptions to this highly precise process may result in wide variety of effects such as abnormal brain function, and it is believed that such disruptions are a major cause of autism spectrum disorder (ASD) and other neurodevelopmental disorders. There are three main cell fates for NSCs: neurons, astrocytes, and oligodendrocytes. The proposed research project deals with the formation of oligodendrocytes, which are the only source of myelin in brain white matter. Myelin is important for overall brain health as it insulates neurons and ensures efficient neuronal communication. Oligodendrocytes and/or myelin formation is perturbed in neurodevelopmental disorders like ASD and schizophrenia, as well as in pediatric neurological disorders like leukodystrophy. It is therefore important to understand how NSCs become oligodendrocytes. Voronova's research has shown that special kinds of neurons called interneurons are responsible for this process through a molecule called fractalkine. The research, of which I played a role, showed that fractalkine signalling directly affects embryonic NSCs and oligodendrocyte formation. Furthermore, scientific literature has shown that fractalkine signalling disruption are present in patients with ASD and schizophrenia, and that genetically-modified mice with perturbed fractalkine signalling show ASD-like symptoms. Thus, it is possible that ASD may arise in part due to aberrant oligodendrocyte formation in fractalkine signalling deficient patients. We wish to further understand how fractalkine signalling functions in embryonic NSCs during brain development and how perturbations in fractalkine signalling lead to aberrant neural development and ASD. In addition, we want to test if fractalkine can promote oligodendrocyte formation from postnatal NSCs. These are a known source of oligodendrocyte formation after birth and represent an excellent target for development and testing of pro-oligodendrocyte formation therapies from NSCs.

What motivated you to participate in this research?

It’s clear that there is a great deal of knowledge regarding the functioning and repair of the brain that can be determined by studying its origins during development; essential processes by which the brain constructs itself are recapitulated as it naturally attempts to repair itself following injury. As such, I believe that studying neurodevelopment is essential to figuring out how we can recruit endogenous processes to promote regeneration in the brain. Furthermore, a wide variety of disorders such as autism spectrum disorder are rooted in neurodevelopment. Thus, understanding the complex events at the root of such disorders will hopefully lead to a greater understanding of each respective disorder, potential therapies and perhaps even preventative measures.

What are your career aspirations?

I'm interested in staying within the realm of the health sciences, whether it is through conducting research, practicing medicine or a combination of the two.

How has this studentship helped you toward those aspirations?

This WCHRI studentship has enabled me to further explore my passion for research in the health sciences. This summer, I’ve had the opportunity to participate in invigorating, exciting experiments that have truly solidified my love for research. Not only that, but I’ve learned so much in the process: about new fields of study, new techniques and more than I can put into words from the experience of working closely with Anastassia Voronova, who continues to inspire me with her incredible passion for science. As such, I'm incredibly grateful to WCHRI, the Stollery Children’s Hospital Foundation and Anastassia Voronova for providing me with this opportunity.