Research Location: University of British Columbia - Point Grey

Salmonella bacteria cause typhoid fever, a frequently fatal infectious condition that is common in the developing world. It also causes gastroenteritis, inflammation of the stomach and intestine. Acquired from contaminated food or water, the bacteria infect and interfere with normal function of cells in the stomach and intestine to cause disease. But precisely how this process occurs is largely unknown. Dr. Nathaniel Brown is studying the function of SifA, a bacterial factor known to play an important role in Salmonella-related disease. Dr. Brown is investigating how Salmonella uses SifA to survive and multiply inside host cells. Results from the research could improve understanding of how Salmonella causes disease and potentially be used to develop new treatments for typhoid fever and gastroenteritis.

Diseases caused by Salmonella bacteria create major health problems throughout the world. Each year, 16 million cases of typhoid fever caused by salmonella worldwide result in 600,000 deaths. Salmonella has also developed increasing resistance to antibiotics. Recent research shows that Salmonella, as well as other related bacteria, use special bacterial proteins called “”effectors”” to facilitate the infection process. These effectors were found to play key roles in the interaction between the host and the bacteria. Dr. Ohad Gal-Mor aims to identify new effectors used by Salmonella typhimurium and to characterize their function. The research could help explain how effectors enable Salmonella to create disease, and contribute to new therapies for controlling bacterial infections.

Mutations in the ELOVL4 gene have been linked with a form of macular degeneration, which is a leading cause of blindness in the developed world. Blindness occurs as a result of a breakdown of the macula, the part of the retina that is responsible for central vision. Researchers can genetically identify families with the disease and describe the genetic mutations that lead to blindness. But how the ELOVL4 gene contributes to normal vision and how mutations cause retina cells to malfunction are unknown. A clue to the function of ELOVL4 lies in its similarity to other genes that help produce fatty acids, which are used to make hormones and the membranes that hold cells together. Fatty acids are particularly important in photoreceptor cells, which are fundamental for vision. Dr. Celene Grayson is investigating the role of ELOVL4 in the healthy retina and how mutations cause blindness. Results from the research could improve understanding of the gene’s function and lead to new treatments for patients with macular degeneration.

Many patients with epilepsy take a drug called valproic acid to control seizures. Although the drug is generally safe, it has been associated (particularly in children) with a rare but irreversible form of liver failure that can be fatal. Despite substantial research efforts in the past 25 years, it’s not clear how valproic acid causes liver failure. Dr. Xiaowei Teng is studying liver cells treated with valproic acid to identify factors that could help explain how valproic acid causes liver failure. Results from this research will help clinicians identify which patients are under high risk of valproic acid associated liver damage. The findings could also serve as a model for preventing similar side effects caused by other drugs.

Salmonella bacteria cause a number of serious illnesses, including typhoid fever, which kills over 600,000 people worldwide every year, and gastroenteritis. When Salmonella bacteria infect human cells, they use the cell’s proteins for their own survival. To accomplish this, the bacteria form a protected area within the host cell that allows them to survive and multiply. A major protein surrounding that protected area is called actin. Dr. Julian Guttman is investigating what other proteins interact with actin and how they affect Salmonella bacteria’s ability to cause disease. The research could provide the foundation for creating Salmonella vaccines or other drugs to eliminate Salmonella-based illnesses.

Nerve cells transmit signals to each other across tiny gaps called synapses. The Purkinje nerve cell receives 150,000 to 175,000 synaptic signals from other nerve cells through synapses that are thought to be major storage sites for information needed to coordinate movement and balance. Loss of Purkinje cells has been associated with numerous neurological diseases and syndromes. Dr. Philippe Isope is studying the role of these synapses in learning and memory. He is investigating how the Purkinje cell is able to select and store information from the vast array of signals it receives. Dr. Isope is also determining if the T-type calcium channel, which has been implicated in a wide range of neurological disorders, filters and ampliflies information from synaptic messages. Calcium channels allow calcium to flow into cells, which supports many cell functions. This research could reveal whether dysfunctions in this calcium channel affect signal integration in the Purkinje cell, leading to learning and memory disorders.

Antibiotics have played a central role in treating bacterial infections ever since the introduction of penicillin. But these drugs struggle to maintain their effectiveness over time as bacteria develop resistance that eventually renders the medication obsolete. Consequently, there is a pressing need to develop new antibiotics. Dr. Andrew Lovering is studying the structure of bacterial proteins. Dr. Lovering aims to identify the exact three-dimensional nature of a group of proteins called glycosyltransferases, which are essential to bacterial shape and form. The research could be the first step toward engineering drugs that block the usual functions of these proteins and fight bacterial infections. In earlier research, Dr. Lovering identified the 3-D structure of an enzyme proposed for use in an anti-cancer therapy. This work contributed to the design of drugs to treat leukemia.