Protein analysis is a bit like studying a stellar object with space probes. Since the 1930s, Pluto was a fuzzy, grainy image, until New Horizons provided a much sharper view of the planet. Similarly, modern protein analysis is able to zoom in close to the action — and could soon be getting as much attention as genetics.
“People think the action happens at the genetic level, but that’s only part of the story,” says Jason Rogalski (BSc ’02) operations manager at the University of British Columbia’s Proteomics Core Facility. “A whole other world opens up when you study proteins. And maybe proteins aren’t the final frontier either.”
Proteins are one of the building blocks of cells and one of the major components of living tissues. A genome encodes information for making proteins, but proteins provide structure to the cells and tissue. Rogalski and colleagues at the PCF use mass spectrometers to study proteins directly.
It’s a combination with a wide range of applications in everyday life. If you’ve ever had your luggage swabbed at an airport you’ve seen a mass spectrometer in action.
Despite this, proteomics labs are relatively recent. The first proteomics lab was founded in 1995 at Macquarie University in Australia. UBC’s PCF launched more than a decade ago as part of the Michael Smith Laboratories, and conducts more than 150 analytical projects a year. One of their longest-running projects is BeeOMICS, which hopes to pinpoint a more resilient honey bee.
Better, healthier bees
Leonard Foster, Head of Biochemistry and Molecular Biology and Director of the PCF, has a long-standing interest in these insects — his parents were beekeepers. With bee populations under threat around the world, finding ways to protect them has become a growing concern for scientists.
“Some bees are more hygienic, meaning they keep their hive cleaner, literally removing dead or dying nestmates from the hive. But only about five percent of bees exhibit this type of hygienic behaviour. We want to help beekeepers find those bees so they can breed more of them,” Foster explains.
This isn’t genetic modification — the scientists aren’t changing the genetic structure of the bees. They’re merely finding the most hygienic ones, allowing beekeepers to breed the most appropriate candidates. More hygienic bees means healthier bees.
“We believe hygienic bees have a certain class of protein which is involved in detecting odours. These odours trigger a grooming impulse, with the odour molecule binding to a protein and sending a signal,” Foster says.
May is bee month at the PCF. For two weeks, beekeepers from across the Lower Mainland ship bees to the lab so they can be analyzed. The researchers study the bees’ antennae, which contain the protein that can signal hygienic behaviour. Because all the worker bees in a hive have a single mother, by looking at a few of these bees the scientists can gauge the state of the whole hive.
“You need 40 bee antennae per colony to get enough protein for analysis,” says Jenny Moon (BSc ‘09), a research technician with the PCF. “The bees are preserved in dry ice, so you take them out and use tiny little forceps and scissors to cut the antennae. We only want worker bees, so you learn to discard the drones.”
Once Foster’s team identifies the most hygienic colonies, they bring the “drone brood” (male bees) from these colonies to the hives, isolated on Bowen Island, where they will mate with a queen and produce a new generation of bees.
Protein analysis is more accurate than behavioral observations and this type of research allows for more effective and faster selective breeding, which is good news for Canada’s agricultural sector.
“Our research shows that you can predict the behavior of specific colonies by understanding their protein structures better,” says Foster. “We don’t need to painstakingly monitor colonies wondering if they are going to be hygienic or not.”
Precious samples
UBC researchers are also analyzing proteins to help patients with spinal cord injuries — injuries that are notoriously difficult to study because we don’t fully understand the biological processes that occur along with the trauma.
“In acute spinal cord injuries, surgeons have no way of knowing what to treat when patients come through the ER door,” Foster explains. “A reasonably high percentage of injuries spontaneously heal. We don’t know why those injuries look identical at an MRI level to those of people who never recover.”
A major barrier to the research is the small number of patients who suffer these injuries. With studies of diabetes, for example, you have a large population of people to look at. That’s not the case for spinal cord injuries. Researchers have to be very careful with the samples.
“With some types of analysis, if things go wrong, researchers can simply go back to the place where they got their samples and obtain more,” says Moon. “That’s not the case with some of the proteins we’re analysing. These samples are precious.”
By combing through some 500 spinal fluid samples collected by spine surgeon Dr. Brian Kwon, at Vancouver General Hospital, Foster’s team has identified proteins which might predict if individual injuries would be likely to heal or not, helping doctors and researchers accelerate clinical trials on new treatments.
Protein whisperer
Work at the PCF can change often and radically. Three years ago, the researchers received a call from RCMP officers who wanted them to test a blood sample for signs of an unknown snake venom.
When it comes to snake bites, people usually know what snake is the culprit, so this was an odd scenario. On top of that, venoms are hard to analyze with a mass spectrometer.
Snake venoms contain unique peptides, and mass spectrometers can work with small quantities of the material. That sensitivity, however, also makes venom analysis cumbersome.
Often protein analysis involves tiny samples, or samples that aren’t clean enough. With venom in human blood, it’s the opposite. Rogalski compares the experience to going through a ‘soup’ of proteins.
“Venom is made of proteins. We are made of proteins. It’s a signal to noise issue. You can hear a pin drop in a quiet room, but not at a rock concert,” says Rogalski. “ With envenomation, you have the whisper of a ghost of a protein in the blood and the struggle is getting enough.”
In the end the researchers were able to pinpoint several venom proteins in the blood sample and informed the RCMP it belonged to two types of rattlesnakes.
But now, with May here, the staff at PCF has switched from snake to insect mode. The yearly shipment of bees will soon arrive and will have to be quickly processed.
“We’ve got two weeks to do this,” Rogalski says. “The bees are not going to wait for us.”
