Manitoba Centre for Proteomics and Systems Biology 10th Anniversary

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1 Manitoba Centre for Proteomics and Systems Biology 10th Anniversary Originally published in HSC Focus Volume 23, Number 6 September 23, 2016 Collaborative and Patient-Oriented Research At HSC Winnipeg, research shapes your hospital experience. From whom you see, to which treatments you receive, to how you rest in your hospital bed, a sophisticated body of research supports your visit to ensure it s the best it can be. This patient-oriented research thrives at the Manitoba Centre for Proteomics and Systems Biology (MCPSB), where several on-going projects work toward improving patient care. One such research project is Dr. Peter Nickerson s search for kidney disease biomarkers: proteins that suggest kidney rejection is likely to occur. Kidney failure is typically detected by a loss of function. But that s a late-stage symptom, says Peter, and requires a biopsy, an invasive procedure. When we talk to patients and there s been a lot of work done in that area what do they fear the most? They fear rejection of their transplant. They don t want go back on dialysis, says Peter. Our goal is to detect rejection early and avoid biopsy if we can. Or at the least, have more strategic biopsies, rather than relying on biopsies alone. Proteomics may provide this possibility. Patients could provide urine samples for easy post-transplant monitoring of proteins that detect rejection early. The benefit? Healthcare professionals could intervene before kidney rejection causes irreversible damage. Patients could keep their transplants in situations where they currently might lose them, avoiding the need for dialysis. This idea is at the heart of Dr. Julie Ho s research project. Her upcoming multi-centre clinical trial will use a new protein biomarker found in urine, which she identified at the MCPSB, to see if she can successfully detect early kidney rejection and improve transplant and patient outcomes. Out of the 2,000 proteins in human urine, this makes her findings significant. I m hoping eventually my research will impact patients, says Julie. You can get a lot of injury before you start to lose function. Our goal is to detect rejection or injury early, before you actually lose function. Collaborations such as these make up the essence of the centre. The space was designed to be open concept with a fusion of basic and clinician-scientists working together. Dr. Hani El-Gabalawy, a MCPSB researcher and one of its founders, says this was its vision from the start. The marriage between clinician-scientists and basic scientists is fundamentally very important for where we want health research to go, he says. We had thought about putting together a group of people who could share resources and whose research programs were similar enough in their approaches that they could share resources and share facilities. Today, Hani runs a rheumatoid arthritis research program in the centre, looking at the cause of rheumatoid arthritis, how it starts, and why. Like both Julie and Peter, he s detecting biomarkers that identify risks, aiming to improve patient outcomes.

2 We use proteomics techniques to analyze the blood samples and tissue samples we get from arthritis patients to help understand the changes that occur in blood, Hani explains. Ultimately, we hope the research is going to help us even prevent rheumatoid arthritis before it ever starts. SOMAscan Assay: Finding a Needle in the Haystack The SOMAscan assay is the most powerful protein biomarker discovery tool available today. It can detect 1,310 human protein reagents in just a few drops, making it a breakthrough proteomics tools for the medical community. And the Manitoba Centre for Proteomics and Systems Biology is home to one of five SOMAscan assays in the world. Researchers at the MCPSB use the SOMAscan assay to detect levels of specific proteins in their samples, looking for patterns of change, consistency, or simply existence. Without such sophisticated equipment, the centre s researchers would have to measure and identify one protein at a time. Research projects like those of Dr. Peter Nickerson, Dr. Julie Ho, or Dr. Neeloffer Mookherjee represent a needle in a haystack, where a very small group of proteins out of thousands in a sample represent something significant in the medical community: either paving the way to better diagnostics and medicines, or better patient-oriented research. Another such researcher is Dr. Kevin Coombs, a virologist at the MCPSB. We re basically exploring what might be considered the next frontier as far as viruses go, says Kevin. Most people who study viruses are interested in the virus itself, because we didn t have tools to study alternative more complicated aspects of viruses than that. But with the tools that the Proteomics Centre has, we can look at very complicated things. Kevin s research project asks a number of questions: What does influenza do to proteins in a cell? How does its effect on proteins cause disease? How can we prevent those disease-causing mechanisms? And how can we better understand how viruses attack a cell? His goal is to figure out a way to modulate proteins to prevent the virus from infecting cells, ultimately protecting the patient while disarming the virus. Kevin hopes to finds something that affects all flu viruses, affecting not only this year s influenza strain, but influenza strains in years to come. The implication of his research would mean patients may only need one flu shot, potentially improving patient health, and the health of society. His lab team is now also using these same approaches to try to better understand how the Zika virus affects host cell proteins. What was really interesting were the proteins that people had never identified before. So, we had close to 100 of these proteins that no one had identified before, simply because they didn t have the tools. But this technology allowed us to do that, says Kevin. The SOMAscan assay isn t the only proteomics tool researchers at the MCPSB are using. The centre is home to a multitude of cutting-edge proteomics machines, limiting researchers only by their imaginations.

3 Better Diagnostics and Medicines Stepping into the Manitoba Centre for Proteomics and Systems Biology is somewhat like stepping into a surreal grocery store. Tall shelves form long hallways that are stocked full with hundreds of bottles of chemicals, beakers of all shapes, several fridges housing specimens, billowing compressors of gas, thick binders, and strange equipment: everything from a Belly Dancer slowly osculating its platform to mix the pink liquids resting in four Petri dishes atop it, to a giant glass SOMAscan assay that s only found in four other labs in the world. But to the researchers at the MCPSB, the shelves represent a wealth of cutting-edge technologies and innovative equipment that offer the potential to do proteomics research. It s a world-class facility, says Dr. Oleg Krokhin, the MCPSB s analytical chemist. I can guarantee you, a lot of people in proteomics, they know about the Manitoba Centre for Proteomics. Oleg is more than the centre s machine operator. The centre s high-profile equipment comes with milliondollar price tags, in some cases for a single piece of equipment, and that requires the technical skills of a professional with an extensive education and background in chromatography and mass spectrometry. That s Oleg, who helps researchers at the MCPSB analyze their biological samples, finding what proteins are present or absent. Oleg says proteomics technology is progressing fast, and the centre does a great job of keeping up-to-date equipment. In 2003, I was sequencing one peptide manually spent hours and hours on it. And right now our analyses, in say 30 hours, can identify 7-8,000 proteins, he says. The centre s noteworthy technology allows immunologists such as Dr. Neeloffer Mookherjee to explore the possibility of developing new therapeutics and approaches to medicine. The two diseases that I focus on are arthritis and asthma. They re chronic diseases, they have public health implications, says Neeloffer. A major problem with chronic inflammatory disease is that many of the standard therapies compromise, in a lot of cases, the patient s normal ability to fight infections. But Neeloffer is examining a small group of molecules that can control inflammation without compromising a patient s ability to fight infections. We believe we have some potential candidates for therapy that can also counter severe asthma, adds Neeloffer. Personalized medicine is an emerging topic in healthcare that proteomics technology is well-suited to address, and has the goal of providing patients with better diagnostics and medicines that are tailored to their individual needs. If you think of an immune system, every person s immune system is wired slightly differently. And because of that, you see that a lot of patients don t respond to certain standard therapies. One therapy for all that s a challenge, says Neeloffer. But understanding the fundamentals of how genes and proteins behave in the body, which centres like the MCPSB do, the easier it ll be to tailor-make diagnostics and therapies. I m trying to fit in this missing gap with a new technology: being able to three-dimensionally simulate an organ in a petri plate inside the laboratory perhaps in a personalized fashion, to predict response to therapy, says Neeloffer. That s the vision.

4 Director s Message The Manitoba Centre for Proteomics and Systems Biology (MCPSB) offers a unique research environment for the molecular analysis of human health and disease. The success of this depends on collaborations between basic researchers and clinician-scientists. The recent addition of novel aptamer-based technologies has enhanced our analytical capabilities, providing an unprecedented capacity to conduct individualized analyses.this represents a critical first step toward realizing personalized medicine. Centre researchers have developed many new approaches that advance our understanding of diverse diseases, with the goal to treat or prevent them. The following pages highlight some of these advances with the hope it will stimulate new collaborative research in biomedicine. Q&A: Director John Wilkins What is proteomics? Proteins are molecules that carryout activities responsible for cell and tissue function. Proteomics aims to identify and measure all of the proteins that are present in a cell, tissue, or biological fluid at a given time. This information could give us a better understanding of what changes in a disease and perhaps how to treat or prevent it. Why was the centre created? There was a local need for proteomics capabilities for basic and clinical research. This arose because of the realization that large numbers of biochemical processes contribute to what we see as health or disease. In order to understand such processes, we needed proteomics to be able to examine as many of these as possible at one time. What makes the research space unique? The lab has an open concept design. This means lab resources are shared, reducing duplicated equipment and capabilities. Many local to national laboratories have now adopted this design. The centre performs basic and clinical research, allowing us to use new methods to study of human health and disease. If we don t do basic research, then we can t hope to do applied research in a very effective way. MCPSB Fast Facts Established in 2006 on the 7th floor of the John Buhler Research Centre A collaboration between the University of Manitoba and the Health Sciences Centre Foundation Provides a collaborative research environment for basic scientists and clinician researchers Offers proteomic capabilities using mass spectrometry and aptamer-based analysis Performs research in diverse areas including immunology and cell biology, virology, transplantation, rheumatic diseases, chemistry, and computational biology Offers a unique interdisciplinary training environment for basic and clinician scientists

5 MCPSB Members John Wilkins, Ph.D. Director, MCPSB Professor, Department of Internal Medicine, Sections of Biomedical Proteomics & Rheumatology, University of Manitoba Neeloffer Mookherjee, Ph.D. Associate Professor, Internal Medicine & Immunology, University of Manitoba Oleg Krokhin, Ph.D. Assistant Professor, Internal Medicine University of Manitoba Peter Nickerson, MD, FRCPC, FCAHS Medical Director, Transplant Manitoba, Winnipeg Regional Health Authority Vice Dean Research, Rady Faculty of Health Sciences, University of Manitoba Julie Ho, MD, FRCPC Associate Professor, Internal Medicine & Immunology, Sections of Nephrology & Biomedical Proteomics, University of Manitoba Transplant Nephrologist, Transplant Manitoba Adult Kidney Program Hani El-Gabalawy, MD, FRCPC Physician, HSC Winnipeg Endowed Rheumatology Research Chair & Professor, Medicine & Immunology, University of Manitoba Kevin Coombs, Ph.D. Professor, Medical Microbiology & Adjunct Professor, Physiology & Microbiology, Rady Faculty of Health Sciences, University of Manitoba