In your fourth year, within the department-based Honors Specialization modules, you will work one-to-one with a faculty member on a novel research project learning about the research process and techniques, while expanding your skills in critical thinking, problem-solving, and hypothesis generation.
Here are just a few samples of research projects you could pursue while in your fourth year.
Understanding cancer metastasis
Cancer is a leading cause of death in Canada and worldwide. The majority of cancer deaths occur as a result of metastasis, the spread of cancer from the primary tumour site to distant organs such as the lung, bone, and brain. Current therapies are non-curative in the metastatic setting, and more research is needed to understand why and to develop new treatments. Research conducted by students in the Honors Specialization programs in Medical Cell Biology are focused on investigating new cellular and molecular mechanisms of cancer metastasis using state-of-the-art cell biology methods and pre-clinical models of cancer. Additional studies involve analysis of cancer patient tissue and blood samples in order to develop new biomarkers and identify new therapeutic targets for metastasis. In the future, these studies could contribute to more personalized and effective approaches for finding and treating cancer.
Stroke and Alzheimer’s Disease
Vascular stress associated with diabetes, hypertension and stroke all increase the risk of developing cognitive impairments such as those seen in Alzheimer’s Disease. Students conducting research in Medical Cell Biology use advanced research tools and techniques to understand the impact of Stroke and Alzheimer’s disease on the brain so that we can develop better treatments for patients suffering from these conditions. Students interested in Stroke and Alzheimer’s disease will receive hands-on training in innovative preclinical disease models, behavioural testing and analysis and molecular and cell biology techniques. Students may also work with leaders in clinical imaging techniques, such as PET and MRI, to visualize changes in preclinical models or the brains of patients suffering from Stroke and Alzheimer’s disease. Overall, students can expect to make meaningful contributions to projects relevant to human disease, directly interact with scientists and clinicians trying to improve the outcome of patients and be part of a vibrant team of investigators dedicated to preserving brain health and cognition.
The protein encoded by the Retinoblastoma tumor suppressor gene (pRB) is one of the most frequently inactivated proteins in human cancer. pRB regulates the cell cycle, likely through interaction with other proteins that control expression of genes important for cell proliferation. To understand how pRB functions, students generate mutated forms of pRB that possess defects in protein-protein interaction domains. Analysis of how mutation of pRB affects cellular responses to signals such as DNA damage will provide insight into how pRB regulates cell proliferation and functions as a tumor suppressor gene. Students will learn techniques such as mammalian cell culture, immunoprecipitation, and Western blotting.
Development of the RNA-guided CRISPR/Cas9 system has revolutionized our ability to edit genomes, although unwanted off-target effects are potentially toxic to cells. Research is working on improving the sequence specificity of genome-editing reagents, including CRISPRs. The goal of this project is to determine the DNA specificity profile of a genetically engineered Cas9 dual nuclease that has been designed to make two cuts in DNA 35 base pairs apart. Understanding the specificity and targeting requirements of this nuclease is essential for its use as a site-specific genome editing tool. Students will learn how to purify protein-RNA complexes, generate randomized DNA substrate libraries, perform DNA cleavage assays, and analyze next-generation DNA sequencing data.
Development of Novel MRI Reporter Genes for Cell Tracking in Patients
Researchers often attach a reporter gene to another gene of interest in tissue cells to indicate whether a certain gene is expressed. Imaging reporter genes are extremely useful for monitoring cell- and gene-based therapies in animal models of disease, and this approach has recently been translated into humans.
This project focuses on combining molecular biology and contrast-enhanced MRI to develop a novel MRI reporter gene that provides positive contrast in areas where engineered cells have accumulated. We believe development of these tools, which presents several opportunities for undergraduate honors projects, will lead to their broad application to following stem cells and immune cells in patients during treatment.
Using Magnetic Resonance Imaging (MRI) to Study Brain Structure
Diffusion MRI measures the random motion of molecules, and this motion is affected by tissue components like cell membranes. The signal we measure can be combined with mathematical models of neural anatomy to learn more about the orientation of axons (i.e. "brain wiring") or how brain cells change in disease. We use ultrahigh field MRI (150,000 times stronger than the earth's magnetic field) to extract even more detailed information than would otherwise possible. Undergraduate honors projects can involve the testing of neuroanatomical models, and/or the analysis of diffusion MRI data acquired in human volunteers.
Phosphate Solubilization by Plant Growth
Plants require phosphate for growth but it can only be absorbed from soil in its soluble form. The goal of one student's research is to identify and characterize bacteria that can solubilize phosphate as well as to examine the gene expression of these bacteria. The findings from this research could help reduce fertilizer applications, which would ultimately decrease insoluble phosphate runoff and toxic algal blooms.
Autoimmune Cells and Multiple Sclerosis
Another student is investigating the use of an insect cell expression system to create proteins that can bind to and detect autoimmune cells that are responsible for driving Multiple Sclerosis.
Macrophages are an integral part of the immune system, especially in clearing unwanted material from our bodies. When macrophages encounter and engulf bacteria, it initiates an immune response to signal an infection. These cells also clear normal dead cells in a similar way, but the macrophage will not signal an infection. One student's project focuses on how macrophages distinguish between bacteria and normal cells, and how it processes these materials differently.
Social determinants of Aboriginal health in Ontario, Canada
This research theme utilizes community-based and ethnographic (cultural) research methodologies to explore the role of social change and adaptation in health outcomes in Northwestern Ontario. The work involves studying the history of the region leading up to the current land use and large-scale mining operations.
Cardiovascular disease (CVD) is a term used to describe all diseases of the heart and blood vessels. One research theme in the One Health program is to understand the factors that affect cardiovascular health in entire communities or populations, not just individuals. These factors include community resources, health care resources, how communities are structured, environmental factors and exposures to pollutants, and policies that affect the communities in which people live. Greater understanding of the factors affecting community cardiovascular health will hopefully, translate into healthier communities and smaller impact of cardiovascular-related disability and death.
Making blood vessels from stem cells
In diseases such as diabetes and cancer, the body loses control over blood vessels that grow either excessively or insufficiently. This research theme in Pathology is aimed at understanding how stem cells participate in new vessel formation so that we may manipulate the process as a treatment for patients with diabetes and cancer. This knowledge generated will also help us to create blood vessels for engineered or transplanted organs.
Identifying the origin of colon cancer
This research is aimed at identifying which cell types produce colon cancer. Using state of the art techniques of labeling different cells in mice, the researchers are attempting to create a signature of the cell type which is responsible for colon cancer. This knowledge can be used to ‘target’ and destroy the cell giving rise to colon cancer.
Therapy with drugs is complex and patients often show a variability on their response to medications. While some patients have the desired therapeutic response, others don’t respond to the drug and even worse, some exhibit toxicity. Research conducted by students in the Honors Specialization programs in Physiology and Pharmacology work to identify why some patients have these undesired reactions to drugs. Students investigate factors such as the impact of disease, genetics and environmental factors, an area collectively termed precision medicine. The goal is to individualize drug therapy to each patient to make treatment of diseases like cancer and heart disease better.
How the accumulation of lipids mediates disease
The North American population is suffering an epidemic of obesity, metabolic syndrome and diabetes. These diseases cause patients to suffer various co-morbidities such as cardiovascular and liver disease. Many of these associated diseases are caused by the accumulation of lipids in various tissues. Research conducted by students in the Honors Specialization programs in Physiology and Pharmacology work to determine how the accumulation of lipids mediates disease and test different treatments to prevent disease progression. The goal is to decrease cardiovascular and liver disease in patients with these conditions.