Year: 2007

Influenza is a severe infection of the upper respiratory tract that occurs each year, affecting approximately 20 per cent of the world’s population. Although vaccination is the primary prevention strategy, a number of scenarios exist for which vaccination is insufficient and for which the development of new antiviral agents would be extremely important. Two classes of drugs are available for controlling the spread of influenza. Amatidines work by blocking the ion channel function of the viral M2 protein. However, these drugs are only effective against influenza A virus and have substantial side effects. The other class of therapeutics, sialidase inhibitors, includes enzyme inhibitors Relenza and Tamiflu. However, influenza viruses are developing resistance to both inhibitors. One solution to the problem of viruses becoming resistant is to use several drugs at once (a drug cocktail), making it more difficult for the virus to develop resistance to all of them. Another solution, which could be used in concert, is to design new inhibitors that are less likely to induce viruses to mutate and develop resistance. This is the goal of Dr. Jin Hyo Kim’s research.

One way of classifying bacteria is by their colour after applying a chemical stain (called the Gram stain). Some bacteria stain blue (Gram-positive), while others stain pink (Gram-negative). Gram-positive and Gram-negative bacteria produce different kinds of infections. Worldwide, more than half of infections treated in hospital involve Gram-positive bacteria. These include Staph infections caused by Gram-positive Staphylococcus aureus bacteria, as well as Strep throat and toxic shock syndrome caused by Streptococcus bacteria. Many Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are becoming resistant to antibiotics. The cell wall of all Gram-positive bacteria contains about 50 percent of teichoic acids, a diverse group of polymers (long-chain molecules). Dr. Leo Lin is investigating whether two common teichoic acids help these bacteria adhere to host cells in humans or even to the synthetic coatings of transplanted medical devices, such as pacemakers. For many bacteria, the ability to attach to the surface of a host cell is an essential first step in the infection process. Dr. Lin will determine the three-dimensional structure of the enzymes that synthesize these teichoic acid polymers using x-ray crystallography, a technique that can deduce the atomic structure of molecules. A lack of teichoic acid significantly destabilizes the bacterial cell wall. Dr. Lin is looking for ways in which this information can be used to develop ways of interfering with the ability of bacteria to attach to host cell surfaces as a first line of defense in protecting against the establishment of bacterial infections.

A protease is an enzyme that can split a protein into peptides. Alterations in normal protease expression are known to be involved in the development of cancer, arthritis and various lung, neurological and cardiovascular diseases. As a result, many proteases and their substrates are an important focus of attention as potential drug targets. Among proteases, matrix metalloproteases (MMPs) are responsible for the proteolytic modification of the extracellular matrix, a complex network of polysaccharides and proteins secreted by cells that serves as a structural element in tissues and also influences their development and physiology. While more is being learned about the multiple functions of MMPs –, many of which are beneficial – their roles and biological functions are not fully understood. David Rodriguez’s research seeks to unravel the complex web of connections among MMPs, their natural substrates, inhibitors and other proteases. He is using a technique known as Mass Spectrometry to detect and identify hundreds, even thousands, of proteins in a sample. By identifying and describing the complex set of signaling pathways in which MMPs are involved, Rodriguez is hoping to better understand the role of these proteases and to predict the consequences when they function abnormally. Such knowledge is critical for designing more effective drugs to treat diseases which result from abnormal protease function.

Spinal cord injury mostly occurs in young people, causing debilitating, lifelong disability. Stroke mostly occurs in older people, and is a leading cause of disability in the elderly. In both cases, recovering function relies on the ability of the central nervous system (CNS) to rewire itself. But the CNS isn’t very supportive of the integral processes required for rewiring to occur. Rewiring requires nerve cells to sprout new fibres (called axons) and subsequently make new connections in the spinal cord by bypassing the damaged area. Rewiring also relies on the birth of new cells that must migrate to the injury site and replace cells that died as a result of the injury. Finally, new blood vessels must also grow back into the damaged area to sustain the regeneration of the new tissue. Each of these processes is controlled by the “extracellular matrix,” the environment surrounding cells. Dr. Adele Vincent is examining how this matrix can be manipulated to improve repair processes in the central nervous system. She is investigating whether SPARC, a protein that regulates interactions between cells and the extracellular matrix, can be used to promote recovery after stroke. Dr. Vincent is studying the role of SPARC in regulating processes that impact on nerve regeneration after injury, such as neural stem cells, new blood vessel formation, and the inflammatory response. Ultimately, these findings could lead to more effective therapies to stimulate regeneration following traumatic injuries, stroke and neurodegenerative diseases.