Reptiles replace their teeth continuously throughout life, as did early mammals, whereas modern mammals do not. If the ability for continual tooth renewal is latent in the mammalian genome, there is potential for the ability to regenerate and replace human dental tissues or whole teeth. This project will use an animal model (the leopard gecko) to seek the triggers that recruit the stem cells that are presumed to initiate replacement teeth.
Possible triggers could range from tooth loss or wear to changes in gradients of molecules secreted by the dental tissues that dictate position and the rate of tooth development. Analysis using high resolution synchrotron scanning and pulse-chase labelling will be compared to studies on tooth extraction previously carried out on iguanas at the Royal Ontario Museum.
Long terminal repeat retrotransposons (LTRR) are the relics of parasitic DNA sequences that are present in the genomes of all mammals, making up about 8 percent of the human genome. They are usually inactive due to chemical modification of their DNA or of the proteins that bind to them. However, certain LTRR are active in specific tissue types and are thought to influence the activity of nearby gene sequences. LTRR are particularly active in the cells that give rise to eggs and sperm and in the early embryo, as well as in cancer cells.
This project will examine LTRR activity in mice using advanced DNA sequencing techniques. We believe the activity of certain LTRR during development of egg cells turns genes on that are important for normal egg production and in the developing embryo.
Our goal is to elucidate how LTRR help drive of gene expression in early embryonic development. This will help us better understand the role that they may play in infertility and potentially in cancer in humans.
This work will investigate three aspects of the role that the immune cells of the brain (microglia) play in stroke — a disease affecting more than 50,000 Canadians every year. First, it will characterize the acute reaction of microglia to low oxygen levels. Second, it will analyze the molecular mechanism by which microglia extend filopodia, thin actin-rich protrusions essential for their role in sensing brain damage. Third, it will examine how microglia, unlike other types of brain cells, can retain their highly dynamic function for several hours in the complete absence of glucose, widely considered as essential for brain energy.
Though vastly different, both the brain and the heart rely on large complicated proteins called ion channels in order to function properly. These proteins facilitate the controlled flow of ions in and out of cells by forming pores that stud cellular membranes. Specialized brain cells called neurons utilize ion channels and the electrical signals they generate to communicate with one another. A repertoire of different ion channels also shapes the birth, growth and development of neurons. During brain injury, ion channel activity can render populations of neurons vulnerable to damage. However, following injury, ion channels can also sensitize surviving neurons and modify their structure and function in ways that allow them to respond, adapt and promote repair. Similarly, the electrical activity underlying the coordinated beating of heart muscle cells is generated by the concerted actions of a cohort of ion channels. It follows that mutations in the proteins that form ion channels can manifest in a spectrum of clinical neurological and heart conditions.
In a series of coordinated projects, Dr. Swayne is working to shed light on how ion channels impact on brain and heart health. Dr. Swayne has been examining the cell biology of pannexin ion channels and their role in neuronal development and injury-triggered plasticity. In collaboration with a group at the University of Ottawa, Dr. Swayne’s team is also studying how probenecid, a drug that stops the function of pannexins, impacts stroke recovery. In parallel, to identify novel ion channel regulators of developmental and injury-triggered neuronal plasticity, her lab is combining basic biochemistry with cutting edge expertise at the UVIC Genome BC Proteomics Centre. Finally, in partnership with the UBC Community Genetics Research Program, Dr. Swayne is also investigating the cell biological underpinnings of clinically relevant cardiac ion channel mutations affecting certain BC First Nations communities.
Overall, Dr. Swayne’s research will bridge critical knowledge gaps in the understanding of ion channel function and dysfunction in the brain and heart.
