The recently acquired mass spectrometer at the Genome BC Proteomics Centre at the University of Victoria offers the promise to revolutionize the clinical identification of the risk of cardiovascular disease, and perhaps scores of other common ailments wherever organs fail.
The potential of this new technology is exciting and will contribute to the work of Dr. Bruce McManus and other researchers with the Centre of Excellence for Prevention of Organ Failure (PROOF Centre).
The Agilent ion funnel 6490 mass spectrometer, through a technique called multiple reaction monitoring (MRM), can determine, in a single pass, the presence and concentration of as many as 150 different marker proteins in the blood, a task that previously required individual tests for each protein.
Set up under a Genome Canada program, the UVic /Genome BC Proteomics Centre is one of many platforms available to the life sciences community through collaborations with the leaders at those platforms. Dr. Christoph Borchers, director of the Proteomics Centre, hosts this high-technology platform and has many collaborations within Canada and internationally.
“The Proteomics Centre has evolved an amazing array of tools for analysis of biological material or specimens that is aimed at identifying and quantifying proteins,” notes Dr. McManus, director of the PROOF Centre.
Dr. McManus’ connection with the Proteomics Centre began in 2004 when he was co-lead on a Genome Canada project that focused on biomarkers in transplantation. The Centre provided the data, while the project was quality-assuring it, quality-controlling it, testing it in its raw form, and synthesizing it to garner real information and results. This collaboration resulted in a very strong relationship with the Centre.
Along the way, says Dr. McManus, “We’ve had various interactions with Dr. Borcher’s facility, including many discussions and work with him toward his dream of making MRM a tool that is not only relevant to fundamental discovery research, but also relevant to the clinical application of research results.”
The PROOF Centre is federally funded through the Government of Canada’s Networks of Centres of Excellence, Centres of Excellence for Commercialization and Research program and has a number of programs focused on critical questions of risk through disease progression — for heart, lung and kidney failure.
The focus of the PROOF Centre is molecular signatures, in the blood or in the urine, to discriminate patients with regard to future expression of disease, to be diagnostic, predictive, or prognostic. MRM is seen as a platform that might make clinical application of the discovery signatures viable.
Dr. McManus explains that the PROOF Centre has established a cohort of patients at St. Paul’s Hospital in Vancouver, B.C., with collaborating investigators Dr. John Hill and Dr. Jiri Frohlich. These patients have had an angiogram — imaging to show whether they did or did not have coronary artery disease or hardening of the arteries in the heart. This population of patients with risk factors for heart disease has been segmented into those positive for disease and those relatively negative for disease.
Using MRM and the blood samples from these patients, Dr. Borchers is conducting a study to determine a correlation between certain protein profiles in the plasma of those with and those without angiographic evidence of disease.
The new mass spectrometer makes this work possible. The MRM is a very fast, very sensitive and very specific. It can measure many, many proteins of interest in a small drop of plasma in a matter of a couple of hours — allowing for a saving in time and biological material needed, while providing the ability to measure many different proteins all at once.
Dr. McManus notes this is just a starting point, characterizing the initial focus, heart disease, as a global scourge, and an important example of where MRM might be useful in understanding the biology underlying the presence or lack of blood vessel disease in the face of standard risk factors.
The ability to identify and quantify proteins that can segment phenotypes in an arteriosclerosis (hardening of the arteries) context, allows for similar work in other settings, such as chronic kidney disease. “Can MRM help us to segment patients into those who are going to have their chronic kidney disease progress versus those who are not going to progress?” poses Dr. McManus.
While working with Dr. Borchers and the Proteomics Centre on the arteriosclerosis project, with a view to other conditions that need risk stratification, PROOF continues work on the Biomarkers in Transplantation initiative, to both validate their markers and to see if MRM is the right tool for clinical use.
According to Dr. McManus, a good partnership or collaboration is never for a single reason, as each team builds on each other’s expertise. In this case, all concerned are very fortunate to be able to build off this technology investment by Genome Canada and Genome BC.
Dr. McManus asserts, “From our perspective, this kind of collaboration reflects the natural desire of scientists to work together and to optimize the return on investment — the value of having invested in technology and programs under Genome Canada, but also the value of investments that have been made into the Networks of Centres of Excellence, like the CECR program. We all want to make a difference socially and economically. ”