Dr. Graham George
Canada Research Chair in X-Ray Absorption Spectroscopy
It’s not only the dose that makes the poison; it’s the form. For instance, the metallic liquid mercury in thermometers is relatively benign. Dimethyl mercury, on the other hand, causes severe, permanent damage, especially to the nervous system.
“It’s not the metal that matters,” says Dr. Graham George. “There are plenty of mercury compounds that aren’t very poisonous and there are plenty of mercury compounds that are actually deadly.”
How mercury does its damage is little understood, and there are few treatment options available. Dr. George is using synchrotron-based x-ray absorption spectroscopy (XAFS) to study how mercury interacts chemically in the body and what forms it takes. This foundation knowledge is critical to designing molecules that can bind to the mercury and carry it out of the system. Such drugs, called chelators, already exist to treat mercury poisoning but they work relatively poorly, particularly against methyl mercury.
Solid knowledge of how mercury chemistry works could also have applications in cleaning up contaminated industrial sites, or even in water treatment plants to remove the metal from drinking water supplies.
“Our goals and our directions are to use the sychrotron to try to understand how mercury is processed biologically and to use that information to develop methods to remove it.”
Dr. George is also using x-ray absorption spectroscopy to explore the structure and function of sulphur in the body.
“We know it is very important but there isn’t much you can do with conventional analysis in terms of looking at the unperturbed living system,” he says.
Sulphur compounds regulate critical cell functions including apoptosis, or the process in which a cell is “switched off” and dies. When this process goes awry, cells don’t die when they are supposed to, leading to maladies like cancer. Conversely, the AIDS virus somehow activates the apoptosis trigger in the body’s defensive T-cells, causing them to commit suicide and to wreak havoc with the immune system. Clear understanding of sulphur chemistry in living systems opens the possibility of designing molecules to regulate cell functions and to treat these diseases.
About a third of Dr. George’s research program is devoted to metalloproteins. Metals form a vitally important part of about 30 per cent of the proteins in our bodies, and they are key to the function of some of the most important biochemisty such as how our bodies consume oxygen, a process that involves both iron and copper.
“Obtaining an in-depth understanding of the chemistry of metalloproteins, including the systems for metal transport and regulation, is one of the most challenging problems we face today.”
Dr. George explains his research is a foundation, the first step in the road to practical application. The mercury problem is an example of this.
“What we’re doing is trying to calculate, using quantum chemical methods, a drug to bind mercury – a custom chelator,” he says. “It’ll bind mercury but it won’t bind other things with anywhere near the same affinity. We’re a long way from actually achieving that.”