University of Saskatchewan scientists have developed a new tool that enables scientists to analyze the function of a crucial set of proteins in animals—a finding that could lead to a host of better drugs for and deeper insights into the workings of cancer.
Developed by a team at the Vaccine and Infectious Disease Organization (VIDO), the tool is described in a Jan. 20th article in the prestigious journal Science Signaling. The technology is expected to be rapidly adopted by scientists in a wide range of disciplines and will likely replace the “mouse model” for some types of research.
“This technology is very simple, relatively inexpensive, and can be adopted in any lab,” said project leader Scott Napper. “Scientists can customize it to look at whatever cell function they want to analyze.”
The new tool—called a species-specific peptide array—involves the use of a glass slide with segments of protein molecules affixed to it. It will help scientists analyze kinases, key regulatory molecules in cells. While only a small percentage of human genes code for protein kinases, mutations in many of these genes are at the root of many human diseases.
Kinases have proven so important as drug targets that pharmaceutical companies have directed 50 per cent of their research and development funding to their study. Targeting kinases can completely alter cell function or turn off cell function that’s out of control.
For the past 30 years, scientists have studied mouse models to understand kinase function. But there are problems with this approach.
“It turns out that mice are different enough from humans that a lot of the results in mice don’t translate to humans,” says Napper. “A number of diseases can be effectively treated in mouse models, but that doesn’t mean we’re making headway with humans.”
The team has found that the new tool helps reveal the “kinome” (the protein kinase complement of the human genome) of other animals, such as cows and pigs. These animals have been shown to more accurately replicate the workings of human disease and immunity than mice—but information about the kinome of these animals has long been minimal.
“This will revolutionize our research,” said co-investigator Philip Griebel. “This technology will allow us to test a hypothesis and very quickly validate the results.”
Scientists will now be able to better understand cell communication pathways in humans and animals, he said.
“We can now do a very rapid screening of the kinases, of which there are hundreds in a cell, and quickly identify which are the key regulatory proteins for any one cell function such as cell division or cell death,” said Napper.
While the traditional method for kinome analysis was to analyze the key regulator proteins one at a time, the new technology allows scientists to look at hundreds of these proteins simultaneously. “This gives us a much more complete view of the regulation of overall cell function,” Napper said.
“Knowing how bacteria or viruses evade the immune defenses of host cells will allow us to develop potential therapeutic interventions such as drugs or vaccines,” he said.
While it may one day help illuminate the cellular actions of cancer, the tool has already shed light on Johne’s—a cattle disease possibly linked to Crohn’s disease in humans but whose mechanism has long stumped scientists.
The team, which includes graduate students Shakiba Jalal and Ryan Arsenault, has already received a flurry of emails from scientists interested in the technique. VIDO hopes to offer the new peptide array as a commercially available kit.
The research is funded by Genome Canada, the Beef Cattle Research Council and Alberta Livestock Industry Development Fund.
- Jalal et al. Genome to Kinome: Species-Specific Peptide Arrays for Kinome Analysis. Science Signaling, 20 January 2009: pl1 DOI: 10.1126/scisignal.254pl1
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