Year: 2007

Cells in the human body are not isolated entities; in fact, they engage in a considerable amount of ‘cross talk’ with other nearby cells. In the most direct form of communication, protein channels pass through the membranes around neighboring cell, allowing small molecules to pass back and forth. These channels, called “gap junctions”, are made up of proteins called “connexins.” Of interest to researchers is the discovery that production of connexins is reduced in aggressive cancers compared to the surrounding tissue. It is due to observations such as this which has led scientists to believe that connexins do more than just form “tunnels” between cells. Stephen Bond is examining the link between connexin 43, the most common form of connexin, and an enzyme called Mgat5. Too much Mgat5 encourages tumour growth, and “knocking out” this enzyme (making it inoperative) increases the amount of connexin 43 protein made. Bond wants to determine whether an increase in Mgat5 increases tumour growth by decreasing connexin 43, and if so, determine how this occurs. This research could identify yet another way in which cells become cancerous, thus increasing our understanding of this class of disease, and hopefully lead to more effective treatments for cancer patients in the future.

Hepatits C virus (HCV) causes chronic liver disease, such as cirrhosis (liver disease) and hepatocarcinoma (liver cancer), an irreversible condition that results in liver failure. There is no vaccine or drug available to prevent or treat this infection, which makes HCV the number one cause of liver transplantation in North America. Host proteins are involved in feeding and sheltering organisms such as viruses. Structural and functional studies revealed that a host protein, glyceraldehydes-3-phosphate (GAPDH) interacts with 3’ non-coding region (NCR) of the HCV genome. This multifunctional protein is also shown to associate with genome of several other RNA viruses, such as hepatitis A virus, hepatitis D virus, human parainfluenza virus type 3, and hepatitis B virus, but its function in the virus life cycle is uncertain. Independent of its glycolitic function, this multifunctional protein is also shown to play a role as an apoptosis mediator upon oxidative stress, and is shown to be essential in endoplasmic reticulum (ER) to Golgi transport. This suggests that GAPDH may be involved in several stages of HCV life cycle, such as regulation of translation and replication by interacting with HCV 3’NCR, modulation of liver damage from oxidative stress imposed by HCV encoded proteins, and formation of new virus partivles by budding of nascent HCV genome through the ER. Meera Raj is researching the biological role of GAPDH in the HCV life cycle, which may include regulating viral replication, facilitating viral assembly and modulating viral release from the host cell. In order to show that GAPDH plays a role in HCV life cycle, Meera has prepared human hepatoma (liver) cells showing reduction in GAPDH expression. Her next step is to study the effects of GAPDH reduction on HCV life-cycle. In order to find other host factors that may play a key role in the HCV life-cycle, she will use microarray to study changes in gene expression within HCV infected cells. Her study will provide insight into the HCV biology, host-viral interaction and may provide a potential new strategy for HCV treatment. Establishing GAPDH as a therapeutic target may also provide a broad base therapy for other infections, because targeting host proteins can affect the life cycles of many other viruses.