What turns cells in the human body on and off? The answer to that question could have huge ramifications for fighting diseases such as muscular dystrophy and cancer. It is a question York kinesiology Professor Michael Connor is busy trying to answer through his multidisciplinary research project, titled "The role of the cell cycle in skeletal muscle development and disease".
All cells in the body start off the same, then they grow and change into hair cells, finger nail cells, organ cells and the like through a process called differentiation. After the cells are fully developed, and while the body is still in an embryonic stage, many cells stop growing in number. Skeletal muscle cells on the other hand, do something a little different. Following initial differentiation, they undergo a further step whereby individual cells fuse together to form tubes of muscles known as myotubes. In addition to wanting to know the secret to what switches these cells on and off, Connor wants to know what triggers some cells to start fusing to form muscle.
"What’s not entirely known is what tells the cells to stop dividing," says Connor (MSc ’94, PhD ’00), a professor in York’s School of Kinesiology & Health Science, Faculty of Health. "So we’re looking at what the underlying cue is that says we have enough muscle cells and so directs them to fuse together. What chemical mediator or signal stops the cells from growing?"
Right: Michael Connor
The answers to these questions could have applications in other fields of research. If researchers know what turns muscle cells on, then it may be possible to activate muscle cell growth in people with muscular dystrophy or in cancer patients and the elderly experiencing muscular wasting (sarcopenia), and it would be equally important to turn cells off in people with cancerous tumours.
"Understanding how muscles grow has a lot of potential for muscle-related diseases, and really not many people have looked at the role of the cell cycle in this process," says Connor. It could also have implications for muscle stem-cell research.
Armed with a 2007 Canada Foundation for Innovation (CFI) Leaders Opportunity Fund award in the amount of $182,853, Connor is in the process of looking into cell development, the impact of the cell cycle and its regulators on skeletal muscle differentiation. It’s an area of research that has received limited attention.
Connor hopes his research will discover the effect electrical activity, which is increased during physical exercise, has on cells. It is currently known that the activity level of a person changes the way the muscles work. So, if a person walks 10 kilometres, following a long period of inactivity, then their leg muscles will hurt. Connor wants to find out if increased electrical activity stops cells from from dividing and, if so, does physical activity impair the healing of injured muscle? This information could prove helpful in knowing how muscle injuries are repaired and whether a person should rest the injured muscle or continue to use it to promote muscle growth and healing.
Satellite cells, which sit around on the outside of the muscle, are charged with growing and repairing the muscles, similar to a stem cell. Looking at cell cycle regulation in skeletal muscle repair will prove important, but examining satellite cells likely won’t happen until year four or five of the research project, says Connor.
Connor is also interested in the role fat cells play in causing cancer, heart attacks, diabetes, strokes and high blood pressure. Here again his research in turning on and off cell proliferation could have a significant effect. Fat cells can surround the body’s organs and in obese people it can act as an endocrine gland and affect the surrounding tissues. These fat cells, once thought to be benign holders of excess energy, are now known to emit numerous potentially harmful molecules into the blood stream and can have a detrimental effect on cancer growth.
"The list of things that obesity is causing is growing and growing. In 10 years, obesity is predicted to be the leading cause of cancer," says Connor. "Part of the problem is that researchers look at all these areas of disease in isolation." Connor wants to know how these things are related. "Is there a link between metabolic rate and tumours?"
With obesity becoming an upward trend around the world, Connor is hoping his research on cells will have wide-ranging applications.
"It’s an open area of research and it’s really overlooked," he says.