The decade prior to 1978 was one of expansion for the Department of Biochemistry involving the acquisition of new teaching laboratory space, the renovation and expansion of research laboratory space, and an increase in the number of tenure-track faculty positions. In contrast, the development of the Department in the three decades following 1978 focuses on a dynamic research program, on the continuous improvement of the undergraduate and graduate curriculum and as always, our students!

What is Biochemistry?

“Biochemistry seeks to explain life in chemical terms. The basic goal of the science of biochemistry is to determine how the collections of inanimate objects that constitute living organisms interact with each other to maintain and perpetuate life. Although Biochemistry yields important insights and practical applications in medicine, agriculture, nutrition and industry, it is ultimately concerned with the wonder of life itself.”

Lehninger Principles of Biochemistry, Second Edition

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Fighting cancer with amazing antibodies

By Lisa Buchanan
December 16, 2011, 10:28 am

A University of Saskatchewan research team has established a national consortium with the University of Toronto to produce synthetic antibodies for diagnosing and fighting cancer and other diseases.
 An antibody is a molecule that can bind to another molecule such as a cancer-associated protein. “There’s no cure for cancer and every cancer patient wants improved therapy. Our main goal is to use antibodies to treat cancer,” said Ron Geyer, U of S Associate Professor of Biochemistry. 

In addition to fighting cancer by targeting cancer-associated proteins, antibodies help with early diagnosis by guiding medical isotopes to tumours. Normally, the human body produces antibodies to fight off disease. They identify harmful cells as foreign and capture them so they can be removed by the immune system. “The problem with cancer is those cells are from us, so our bodies don’t recognize them as foreign and we are incapable of producing antibodies against ourselves,” Geyer said. Over the past decade, antibodies have become the major breakthrough for cancer treatment. Geyer has established the Saskatchewan Therapeutic Antibody Resource (STAR), a research group of a dozen scientists that will develop synthetic antibodies. STAR is seeking funding to open a dedicated laboratory centre for large-scale operations.

Geyer is using cutting-edge technology to produce antibodies that are more specific, and cheaper and faster to generate than with the conventional method. Unlike traditional methods of antibody production, synthetic antibodies are developed in a test tube rather than in the immune system of an animal. STAR is part of a new consortium established with the Toronto Recombinant Antibody Centre at U of T. The consortium members will pool their expertise to produce more and better antibodies. There is a need for new antibodies because they are not available for every target. There are only about a dozen antibodies approved for therapy. The market for antibody therapeutics is estimated at more than $26 billion annually worldwide. The consortium will enable rapid commercialization and develop a network for producing sufficient quantities of therapeutic and diagnostic grade antibodies. STAR will generate antibodies for researchers in Western Canada. “We would provide high-quality human antibodies that recognize human proteins important in diagnosing, monitoring, and treating diseases,” Geyer said.

Since our bodies do not recognize cancer cells as harmful, antibodies must be engineered to detect specific defects in cancer.  That’s where researchers like Geyer and his colleagues come in. They produce billions of unique antibodies from which they isolate those that recognize a target, such as a cancer cell.  The disease target is exposed to the pool of antibodies to find out which one binds to the target. STAR plans to collaborate with the Saskatchewan Cancer Agency, the Vaccine and Infectious Disease Organization and International Vaccine Centre (VIDO-InterVac) to develop antibodies to detect infectious disease, the Canadian Light Source to generate antibodies for imaging and structural biology, and with other organizations to develop antibodies for agricultural applications. Antibodies will also be used by the new cyclotron planned for the campus which will produce medical isotopes for Saskatchewan’s first positron emission tomography-computed tomography (PET-CT) scanner to be installed at Royal University Hospital. Isotopes produced by the cyclotron reveal tumours in a PET-CT scan, but the isotopes cannot find their way to the tumour on their own. The isotope can be attached to an antibody which guides the isotope to the tumour. “The PET-CT scan can show a number of things including where the tumour is, its size, whether it has spread, or if it is in remission, shrinking or disappearing,” Geyer said. While other methods exist for showing this, Geyer explains that antibodies allow for a more targeted diagnostic which could lead to earlier detection. “One of the main goals in cancer research is early detection because a lot of tumours are worth operating on as long as they have not spread.”

 

 

Dr. Scott Napper Biography

Dr. Scott Napper holds a joint position at the University of Saskatchewan as an Associate Professor of Biochemistry as well as Senior Scientist and Program Manager of Emerging Diseases at the Vaccine and Infectious Disease Organization (VIDO). A protein biochemist by training, his research interests are based in the application of structure activity investigations within the context of infection and immunity. Specifically, his currently active research programs include structural modifications of host defense peptides for immunotherapeutic applications (vaccine adjuvants and antimicrobials), vaccine development for Johne's Disease and development of a PrP^Sc specific vaccine for prion diseases. Dr. Napper's work in development of a prion vaccine is centralized in the optimization of epitopes to maximize immunogenicity, while maintaining PrP^Sc specificity, as well as the application and optimization of various parameters of vaccine formulation and delivery. Outside of the lab Scott has a strong interest in Science Education and works actively with the Secondary Education System to help translate higher level science and mentorship to undergraduate and high school students. In the past five years, Scott has twice been awarded the University of Saskatchewan Teaching Excellence Award.

Current Research Interests:
1) Prion diseases in a variety of mammalian species are characterized by the conversion of the normal host protein (PrPC) to an abnormal infectious form (PrPSc). A research team led by Dr. Neil Cashman has identified and characterized a surface-exposed antibody-binding site which is present on PrPSc but not PrPC. This site is conserved among PrPSc of a wide variety of mammalian species, thus making it an excellent universal vaccine target for prevention and therapy of diseases such as BSE and CWD. The primary objective of this proposal is to develop vaccine formulations and vaccination protocols f which generate sustained levels of antibodies that react specifically with PrPSc but not PrPC.

2) Johne's Disease: Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease, a chronic inflammatory disorder of the gastrointestinal tract of ruminants . Johne's disease is of considerable economic importance in dairy cattle as it is responsible for the highest average production losses among five production-limiting diseases. There is additional growing concern that MAP may be a causative, or contributing, factor to Crohn's Disease in humans. The potential zoonotic threat, and realized economic impact, of Johne's Disease has energized efforts for development of an effective disease management strategies. However, the limited success of traditional approaches to vaccine design for Johne's disease indicates that greater understanding of the biology and virulence mechanisms of MAP is required to adopt a more strategic approach to vaccine design. Specifically, an understanding of the mechanisms by which MAP subverts host immune responses could form the basis for development of vaccine formulations and strategies.VIDO recently instigated a Johne's Disease Program focused on development of an effective vaccine and/or therapeutic. Since its inception our group has developed three key platforms to be applied to the current proposal: 1) Development of a novel technology for characterization of global kinase activity (the kinome) in bovine cells, 2) Identification of immunotherapy treatments that clear MAP from infected monocytes and 3) Creation of a stable bovine gut loops for characterization of acute and chronic host responses to MAP infection. These tools will collectively enable us to achieve a greater understanding of the virulence mechanisms of MAP. We believe that understanding the mechanisms by which the bacterium subverts host immune responses will form the basis for development of an effective vaccine and/or therapeutic.

3) Kinome Analysis Phosphorylation represents the pivotal mechanism for regulation of cellular processes, and kinases are one of the most biologically important classes of enzymes . The regulatory roles of kinases in cellular pathways and disease, as well as their conserved catalytic cleft, make them attractive targets for drug therapy. The therapeutic and biological importance of kinases has prompted the development of novel strategies for quantification of their activity. Sites of protein phosphorylation and their subsequent biological consequences are often conserved; therefore, it should be possible to predict the sequence contexts of phosphorylation events in proteins of other species on the basis of genomic information. To demonstrate the feasibility of this approach, we selected a set of phosphorylation events that represent the major signal transduction pathways, with an emphasis on pathways and processes relating to innate immunity. We then created a bovine peptide array for kinome analysis and have successfully applied this technology to several diseases. Species-specific arrays for other non-traditional laboratory species are being pursued.

For publication information please visit PubMed.

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