Research Location: Simon Fraser University

The pacemaker cells of the heart are a small group of cells that beat spontaneously and set the beating frequency. On the surface of these cells are “pacemaker channels”, which open and close to allow potassium and sodium ions into the cells. The flow of these ions into the cell generates the spontaneous beating in the heart. The speed at which ions flow through the channels regulates how fast the pacemaker channel opens and closes, which in turn can affect heart rate. During exercise and stress, the amounts of these ions in the blood change and may affect the rate at which these channels open and close, leading to irregular heart beat. For a small group of people with heart disease, an irregular heart beat can be dangerous and potentially fatal. Vincenzo Macri is working to determine how the function of pacemaker channels are affected by the flow of sodium and potassium ions. He is using several molecular and cellular experimental approaches, such as patch clamp electrophysiology, DNA mutagenesis, cell culture and cellular imaging to learn about the structure and function of this important protein. By understanding how this process works, he hopes his research may lead to therapies that target these channels to control the onset of irregular heart beats.

Each year millions of people worldwide are diagnosed with diseases related to disordered protein folding. Normally, protein chains fold into a defined shape in order to function properly and when this process is disrupted, diseases such as Huntington’s, Alzheimer’s, cystic fibrosis and some forms of diabetes occur. The regulators of protein folding are called molecular chaperones, and as the name implies they have an important, but not well understood, assistive role in the process. Many molecular chaperones are essential for a cell’s survival. Some chaperones have been directly linked to the causes of genetic disorders involving misfolded proteins but others have been shown to be involved in slowing and preventing neurological diseases like Alzheimer’s. Peter Stirling’s research focuses on a protein called phosducin-like protein 3 (PhLP3), shown to be involved in facilitating protein folding as it interacts with an essential chaperone called CCT. Peter aims to understand how PhLP3 affects protein folding and what functional consequences the PhLP3-CCT interaction has. Peter’s research will help answer fundamental questions about how cells efficiently generate and maintain properly folded proteins, which will ultimately help to better understand what is happening in a cell when protein folding is disordered. His results may eventually lead to better treatment for diseases associated with protein misfolding.

Arthropod-borne viruses (arboviruses) are viruses transmitted to plants and animals by insect vectors, such as mosquitoes and ticks. In human and animal populations around the world arboviruses such as West Nile virus continue to cause significant morbidity and mortality. To date, research efforts around these viral diseases have focused almost entirely on humans. There is however another important aspect to the disease dynamics, which has not been addressed, and that is the effect of these viruses on the insects that transmit them. The insect immune system shares many features with the human immune system yet very little is known about how insects regulate viral infections. Research has shown that arboviruses somehow evade the insect’s immune system yet are capable of transmitting the viruses to other hosts. Dawn Cooper is examining what factors viruses use to develop in insect vectors and the factors that insects use to kill viruses. Her research focuses on characterizing the immune responses expressed in response to the virus infection of Aedes aegypti, a major vector of arboviruses. Ultimately information gained through this study will identify the novel fighting components of the insect immune response which may be exploited to reduce transmission or develop drugs to treat human infections.