Year: 2004

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.

Infectious diseases are responsible for up to a third of deaths reported worldwide. A large percentage of these deaths are directly related to bacterial infections. Bacterium that cause infections, such as E.coli, thrive because of their ability to rapidly adapt to changes in their environment. The ability to rapidly adapt stems from tight control over the expression levels of proteins within the bacterium. The messenger RNA (mRNA) is a template that codes for proteins ready to be expressed within the cell. The instability of mRNA allows E.coli bacteria to quickly change the expression levels of proteins within the cell in order to adapt and survive when it invades a host cell. E.coli employs a protein complex called the RNA degradasome to degrade mRNA for this purpose. Using X-ray crystallography (a technique for determining the 3D structures of molecules), Dr. Trevor Moraes is researching how the RNA degradasome functions. This analysis of key processes involved with disease-causing bacteria could contribute to the development of new antibiotics to fight bacterial infections.

Alzheimer’s disease is the most common neurodegenerative disorder causing dementia in older people. With Alzheimer’s, brain cells shrink or disappear and are replaced by irregularly shaped spots or plaques. The amyloid beta (A-beta) protein is a central component of these plaques. A-beta is a normal part of brain cells, but is toxic in high concentrations. Dr. Yigang Tong is studying why there is an increase in A-beta proteins with some older people. He is focusing on the role of the BACE enzyme that produces this protein because he believes degradation of this enzyme is impaired, allowing the amount of A-beta to increase in brain cells. Identifying the steps involved in the degradation of the BACE enzyme could help explain how Alzheimer’s disease develops and potentially lead to new drugs to treat the condition.