Research Profile - Exploring nature’s medicine cabinet
Dr. Dieter Brömme
A UBC researcher screens bacteria for compounds with potential health benefits
The search for new medications is big business. This search typically takes place in laboratories at universities and pharmaceutical companies. But many of the medications on the market today, from painkillers to cancer therapies, were formulated in nature's laboratory – they were originally derived from plants and other natural products.
Dr. Dieter Brömme, a researcher at the University of British Columbia (UBC), has returned to this laboratory in search of new drugs to control osteoporosis and inflammation. Dr. Brömme is combing the diverse microscopic life forms of B.C.'s rainforest for new substances that stop the activity of cathepsin K and cathepsin S, chemicals in our bodies that play an important role in osteoarthritis and inflammation, respectively.
At a Glance
Who – Dr. Dieter Brömme, Professor, University of British Columbia
Issue – The enzymes cathepsin K and cathepsin S play important roles in diseases such as osteoporosis and arthritis.
Research – Dr. Brömme and his team are studying the chemicals found in the diverse bacteria of the B.C. rainforests to see if they can identify and isolate a safe cathepsin inhibitor.
Impact – A safe and effective inhibitor for cathepsin K or cathepsin S could lead to a new osteoporosis or arthritis medication. Dr. Brömme’s research is adding to our understanding of the connection between biodiversity and human health.
Cathepsins are a group of proteases – a type of protein found in our bodies that break down other proteins. In the early 1990's, researchers discovered that cathepsin K plays an essential role in bone degradation, and therefore is a pharmaceutical target for arthritis and osteoporosis drugs. This discovery prompted the search for safe, effective cathepsin K inhibitors.
"We knew that various cathepsin inhibitors were derived from bacteria," says Dr. Brömme. "We thought, considering the huge diversity of bacteria, there must be more than the three or four known bacterial compounds that inhibit cathepsins."
Dr. Brömme is an enzymologist by training, and not particularly familiar with the bacteria and plant-life of the B.C. rainforests. But UBC is home to an impressive catalogue of local bacteria and lichen species.
"Dr. Julian Davis, a renowned microbiologist, began amassing a collection of bacteria and lichen species at UBC in the hopes of identifying new antibiotics," says Dr. Brömme. "He collected around 3,000 microorganisms from the plants and soil in B.C.'s rainforests."
With the help of funding from the Canadian Institutes of Health Research, Dr. Brömme and his team screened each organism in Dr. Davis' library to see if they produced potential cathepsin inhibitors. He and his team found that approximately 10% of the species had fairly high activity against cathepsin K and S, and they identified three species of bacteria that contain promising inhibitors. They are now in the process of trying to isolate and identify these compounds.
"Screening a single organism (to see if it contains a potential inhibitor) is fairly easy – it's almost immediate. It helps that we know what we're looking for. The tricky part is trying to isolate the compound," explains Dr. Brömme. "In order to produce enough of the compound to isolate it, we typically have to grow 20 litres or more of the bacteria. Sometimes the bacteria's phenotype will change during the growth and it will stop producing the inhibitor, so we'll have to start from scratch again."
But growing the bacteria is just the beginning. Then Dr. Brömme enlists the help of Dr. Ray Andersen, a researcher in UBC's chemistry department, to extract the cathepsin inhibitors from the bacteria. Once they've isolated each compound, they will use several techniques, such as x-ray crystallography and nuclear magnetic resonance spectroscopy, to determine the inhibitor's physical structure, both in its pure form and when it is bound to the cathepsin enzyme.
"This will give us valuable information about how the inhibitor fits into the active site on the enzyme," explains Dr. Brömme.
Dr. Brömme and his team are tapping into the biodiversity of B.C.'s forests to improve human health. He feels it's important to recognize the value in exploring and preserving the biodiversity around us.
"Nature has had more than 3 billion years to make a multitude of compounds. Humans have only been around for a short time, and we've been practicing chemistry for an even shorter amount of time," says Dr. Brömme. "There are many natural compounds that have not yet been described. When we destroy our environment, we risk losing these valuable compounds forever. We are burning down the library."
"There are many natural compounds that have not yet been described. When we destroy our environment, we risk losing these valuable compounds forever. We are burning down the library."
-- Dr. Dieter Brömme