Research Location: University of British Columbia - Point Grey

Mild electrical stimulation of various brain sites leads to the development of seizures, which intensify over time. Called the kindling phenomenon, this process has been widely studied as a model of epilepsy, neuroplasticity (learning, memory and various mental disorders) and the interictal (emotional) changes that occur between seizures in certain types of epilepsy. In his previous research, Steven Barnes demonstrated that learning plays a major role in this process. His studies show that rats learn to associate particular environments with seizures and this awareness greatly affects the intensity of seizures and interictal behaviours. People with epilepsy also tend to have more seizures in certain situations than others, a pattern that has not been widely studied. Steven is investigating how conditioning affects these responses. His research will ultimately reveal insights about the role of conditioning in the kindling phenomenon associated with epilepsy.

White blood cells are the key elements of the immune system that keep our bodies healthy. Normally these cells circulate in the bloodstream, but upon infection or injury, the cells exit from blood vessels and enter the damaged tissue to promote healing. Proteins on the cell surface, called cell adhesion molecules, take white blood cells to the afflicted site. These molecules are tightly regulated to ensure they only allow cell migration into damaged tissues. When regulation fails, cell adhesion molecules may promote inflammatory diseases such as arthritis, inflammatory bowel disease and atherosclerosis or metastasis (transfer from one organ or body part to another) of cancer. Kelly Brown is studying CD44, a cell adhesion molecule found in mice and humans on virtually all cell types. Kelly is investigating CD44 on particular white blood cells called monocytes. Once in damaged tissues, these cells eliminate pathogens and alert the rest of the immune system. She is examining the changes that occur in CD44 when monocytes are activated and how the regulation of CD44 contributes to monocyte function during an inflammatory response. Kelly ultimately hopes to learn how to block or promote CD44, which could lead to new treatments for inflammatory diseases and cancer.

Pulmonary hypertension (PHT) is a life-threatening disease; people with PHT experience shortness of breath, chest pain and fainting and live an average of 2.5 years after diagnosis. The disease involves increased production of endothelins in the lungs, which constrict blood vessels in the lungs. Endothelin is a potent vasoconstrictor (constrictor of blood vessels). Xing Cheng is investigating how certain substances produced in the lungs with PHT influence the ability of endothelin to constrict blood vessels. She is also examining how anti-inflammatory drugs that inhibit the formation of these substances affect production of endothelin. Her research will help identify drug combinations that may reverse the cardiovascular abnormalities causing pulmonary hypertension.

The Ichthyosporea are a group of single-celled parasites that infect a variety of animals, including humans. The group has only very recently been identified on the basis of some preliminary genetic data, and appears to have evolved from animals and fungi. Very little is known about these parasites, and genetic data is needed to understand their evolution and how they function. Audrey de Koning is determining the DNA sequences of some common genes in several Ichthyosporeans and comparing these sequences to the genes of other organisms. This will allow her to identify similar genetic patterns and learn more about how Ichthyosporeans evolved. She is also generating a large number of DNA sequences for expressed genes-genes that have had their coded information converted into the structures present and operating in a cell-in a representative member of the Ichthyosporea. This will give a broad picture of how these parasites function, and may uncover weaknesses that can be exploited to develop new disease treatments.

The bacteria Enteropathogenic E. coli (EPEC) is a major cause of infantile diarrhea, killing an estimated 100,000 children every year. (The bacteria is also closely related to enterohemorrhagic E. coli 0157:H7, which causes hamburger disease.) Most bacteria attach to existing proteins on host cells to cause disease. EPEC inserts its own protein into host cells and then attaches itself to the protein. Annick Gauthier is studying a specialized transport system—called a type III secretion system—that is believed to deliver this necessary protein from the EPEC bacteria into host cells. Her goal is to understand this fundamental mechanism, which is found only in disease-causing bacteria. Learning how this system works could provide targets for both vaccine and antibiotic development that would harm only the disease causing E. coli, and not the healthy bacteria that normally reside in the intestine.

Proteins called calcium channels regulate how calcium gets into nerve cells. In nerve cells, calcium channels control a variety of normal physiological responses including muscle and heart contraction, hormone secretion and the way neurons transmit, receive and store information in the central nervous system. When too much calcium enters these cells through calcium channels, a number of disorders can result, including congenital migraine, angina, epilepsy, hypertension and stroke. Michael Hildebrand is studying calcium channels called T-type channels, responsible for neuron firing, the nervous impulses that occur throughout the nervous system. Michael is investigating the structure and function of these channels to determine how they activate or inhibit calcium. He is also investigating drugs that can block specific channels to develop new treatments for epilepsy and various cardiovascular diseases.

Bacterial resistance to antibiotics is on the rise and poses increasing threats to susceptible individuals, including the elderly, children and immunocompromised patients. To develop new and effective therapeutics against these microbial enemies, a thorough understanding of their pathogenic (disease-causing) mechanisms is required. Calvin Yip’s research focuses on characterizing the structural components of the bacterial type III secretion system (TTSS). Found in many pathogenic bacteria-including Enteropathogenic E. coli and Salmonella strains-these secretion devices are essential to the bacteria’s ability to cause disease. These systems allow pathogenic bacteria to deliver effector molecules into human cells, where they disrupt normal cellular function. Calvin is investigating how the TTSS structures are assembled and how they deliver effector molecules into cells. In conjunction with other biophysical studies, this work will result in a deeper understanding of the assembly and function of TTSS and may provide the basis to design new drugs.