Associate Professor, Division of Medical Sciences
Phone: (250) 853-3723
Research area: Bioelectric control of neural stem and progenitor cells; neural stem cells in brain repair; pannexins and voltage-gated sodium and calcium channel superfamily members: structure, function and regulation by protein-protein interactions.
Although the last decade has seen some spectacular advances in neuroscience, getting neurons to regenerate on demand is tantalizingly out of reach for a group of neuroscience researchers at UVic who would like to lessen the dignity-robbing effects of Alzheimer’s, Parkinson’s and stroke. The most recent addition to this research group, Dr. Leigh Anne Swayne of the Island Medical Division, is following up on her success in an exciting new area of brain research: the role of pannexin proteins.
To back up a little and explain the extent of the challenge to repair brains, Swayne explains that neural stem cells are rare (they are only found in two parts of the brain) and very tightly controlled in ways that we don’t yet understand.
“We don’t even know how to get the stem cells to the site of damage,” she says.Ideally, we’d fully understand the mechanism that control neural growth in order to manipulate them to help a patient recover damage to the brain. It was this promise of many new and important proteins yet to be discovered in the brain that led Swayne to look at a recently discovered family of proteins called pannexins.
Pannexins are interesting for several reasons. They are closely related to connexins (proteins that form gap junctions between cells, an important way that cells communicate with each other in vertebrates). Pannexins were discovered when researchers starting combing the wealth of genome data that started to emerge in the last decade, looking for proteins in higher animals that corresponded to connexins and innexins (the invertebrate version of connexins). The result was a family of distinct proteins that are extraordinarily ancient, and found in most living multicellular organisms. Unlike connexins that usually connect cell-to-cell, pannexins often just make hemichannels, connecting a cell to the extracellular space. But most intriguing, they are found in the brain, where there were immediate signs that they were involved with neural development.
“I like to think of them (hemichannels) as tasters of the environment -- testing ions, metabolites, signaling molecules,” says Swayne. This might explain how pannexins can have an effect on cell signaling and cell development.
Thus pannexins became a hot area of research and Swayne was at the forefront of adding to this excitement during her time as a post doctoral fellow at the University of Ottawa, when she discovered that the gap junction Panx2, acts like a gate keeper to neurogenesis, holding neural stem cells in their stem cell state, until Panx2 is told to stand down.
Swayne was drawn to UVic in 2010, in part because of the synergy that is starting to happen in neuroscience on the West Coast. Swayne feels UVic is the perfect place to combine her molecular background (she started in protein and lipid biochemistry), with whole organism studies and behavioural studies already going on at UVic and UBC.
“I remember the first time I held a brain in a neuro-anatomy class during my PhD, and I thought, ‘This was in someone’s head, and they thought with it.’ It was very weird,” she says. Ever since then Swayne’s wanted to gradually broaden her research scope so she could relate cellular mechanisms to what is going on in a thinking, feeling, learning individual, which is something she plans to do here at UVic.
But for now, as she builds her new neuroscience lab, her research focus is to understand the molecular mechanism of neuron regeneration, starting with building on her success with pannexins.
Looking forward, she is full of questions, such as: when and how are pannexins normally expressed? What signals are carried by pannexin channels, and how do those signals change a neural population?
For part of her research, she is collaborating with UVic neurobiologist Dr. Craig Brown (also in UVic’s Division of Medical Sciences), who has been working with mice to understand neural regeneration following brain damage from a stroke. Apparently after a stroke, brains will undergo a massive proliferation of new neural cells, but the majority of these new cells then die. Swayne explains that a natural question is to wonder, what if you could prevent some of those cells from dying? Would it improve recovery?
Swayne is working with Brown’s mice model to test whether pannexins are involved in the proliferation and death of cells following stroke, and if these signals can be manipulated – without causing a loss of cell growth control. Not surprisingly, one of Swayne’s colleagues, Dr. Christian Naus at UBC, has found a connection between Panx1 and Panx2 and brain cancer, which is both encouraging – it strengthens the theory that pannexins controls cell growth ‑ and discouraging. Clearly there is much work to be done before a brain repair therapy is developed.