Faculty

Lindsay Robinson

I am interested in understanding the physiological roles and regulation of adipose tissue and skeletal muscle-derived cytokines in mediating metabolic processes in the body. I am particularly interested in the mechanisms by which dietary factors and/or exercise modulate various cytokines and inflammatory mediators implicated in insulin resistance, a key characteristic of obesity and type 2 diabetes. My current research projects are:
1) Regulation of adipose tissue-derived cytokines in integrative metabolism.
2) Effect of n-3 and n-6 fatty acids in the presence and absence of LPS on adipocyte secretory factors and underlying mechanisms.
3) Effect of dietary fatty acids on pro-inflammatory markers in an in vitro murine adipocyte macrophage co-culture model.

Coral Murrant

My main research focus centres around the issue of how contracting skeletal muscle can communicate with blood vessels in order to ensure adequate blood flow to the working skeletal muscle cells. There is a direct relationship between skeletal muscle metabolic rate and blood flow. This type of relationship requires that active skeletal muscle cells communicate their need for blood flow to the cells of the vasculature, endothelial cells and vascular smooth muscle cells, and that these cells alter their function in order to ensure the proper blood flow delivery. I am interested in this intercellular communication. The current thinking is that skeletal muscle cells release vasodilatory products which are end products of metabolism, and these products diffuse to effect the vasculature. Currently we are testing this hypothesis by contracting the skeletal muscle in various ways as to change its metabolism and determining how the different metabolic rates alter the microvasculature. We are also testing for what these specific diffusable products are and how they alter endothelial cell or vasculature smooth muscle cell function.

Jeremy Simpson

My lab conducts research on several areas related to cardio-respiratory physiology and pathophysiology. For example, we are studying: 1) how the heart initially adapts to hypertension before the development of contractile dysfunction and heart failure; 2) skeletal and cardiomyocyte cell signalling during normal and hypoxic conditions; 3) proteomic alterations that occur in limb muscles during exercise; 4) key post-translational modifications of myofilament proteins that arise during the development of whole muscle dysfunction as a result of fatigue or ischemia; and, 5) dyastolic dysfunction in various physiological and pathological states, such as aging, sex differences, and models of heart failure.

David Wright

Since changes in how the body metabolizes glucose are a hallmark of Type 2 diabetes, understanding how the function and metabolism of adipose tissue are regulated will be crucial for understanding diabetes itself. My students and I look at how exercise and nutritional interventions affect gene expression in adipose tissue, and, in turn, how these changes can affect both adipose tissues metabolism and the whole bodys glucose metabolism. One of the applications of my research is to potentially develop new, non-drug-based approaches that can be used to prevent and/or reverse Type 2 diabetes.

Lori Vallis

Purposeful action requires the central nervous system to integrate, into ongoing movement patterns, available sensory information about body position in space. Vision is a unique sensory input as it provides this information in advance, for route-planning, and the adjustment of on-going stepping strategies. To date, my research program has focused on strategies used to execute safe movement during adapted locomotor tasks (steering, obstacle circumvention, obstacle stepping) and the role of vision in these tasks.
I am also interested in exploring the impact of cognitive or brain function on locomotor control. The reality is, we routinely perform mental tasks while walking in busy, dynamic environments (e.g. listening to a loudspeaker announcement while walking through a busy shopping mall) and recent research indicates that performing more than one task at a time influences our walking performance. Given the commonness of dual tasking in our daily living, I hope to map patterns of cognitive-locomotor interference for multiple adapted locomotor (e.g. obstacle circumvention) and cognitive activities (e.g. visuo-spatial cognitive tasks) and ascertain optimal training strategies for dual-task performance.

Marica Bakovic

My background is in molecular and cell biology of lipid metabolism. Currently, my students and I work on the regulation of membrane phospholipids, fatty acids, and methyl-group donors. More speficially, we look at regulation of genes involved in choline transport and phospholipid metabolism; nutrient transporters and kinetics of membrane transport; molecular and cell biology of lipids; the effect of nutrients on protein synthesis and gene expression; and, nutritional genomics (nutrigenomics) of risk factors for cardiovascular disease and insulin resistance.

Baozhong Meng

The ultimate goal of my research is to understand viruses and viral diseases for the betterment of agriculture. This goal is being achieved through investigations using multi-disciplinary approaches including those used in virology, molecular biology, cell biology and biochemistry and through national and international collaborations. Our research involves a number of important viruses that infect plants, which include Grapevine rupestris stem pitting-associated virus (GRSPaV), a ubiquitous and important pathogen of grapes worldwide. Current research directions include: Processing and subcellular localization of the replicase polyprotein of GRSPaV; elucidation of function of the novel Alkylation B (AlkB) domain in the replicase polyprotein of GRSPaV and closteroviruses; structure and cellular localization of viral replication complexes; evolution biology and bio-informatics of major grapevine viruses; development of virus-induced gene-silencing vectors for beneficial applications; and, development and application of highly efficient and economical technologies for the diagnosis of major grapevine viruses.

Terry Van Raay

Many of the signaling pathways that are involved in development are also involved in the onset and progression of disease. As an example, the Wnt signaling pathway is required during many stages of development and in the homeostasis of stem cells in the adult. Perturbation of this pathway in stem cells in the adult often leads to cancer. It is now known that greater than 90% of colorectal cancers are caused by mutations in the Wnt signaling pathway. As this pathway is important for both proper development and disease, I am curious to know how this pathway can turn it self on and off so many times during development and why it fails to turn off in disease.
The lab focuses on two negative feedback regulators of Wnt signaling: Nkd1 and Axin2. Both of these are induced by Wnt signaling and so far appear to be obligate and universal targets of Wnt signaling within vertebrates. Using zebrafish as as in vivo cell models, we are testing the hypothesis that Nkd1 is somehow activated on the plasma membrane by a Wnt ligand. Upon activation, Nkd1 moves from the membrane into the cytoplasm to inhibit the nuclear accumulation of ?-catenin, which is the central signaling molecule of the Wnt pathway. Due to the nuances of cell culture we cannot observe this phenomenon in vitro, but have found that Nkd1 can be artificially activated in cancer cells, potentially inhibiting their growth. Currently, we are trying to determine how Nkd1 is activated and what affect this has on the cancer cells. We are also studying Axin2, which is expressed at the same time and in the same place as Nkd1. We have evidence that Nkd1 and Axin2 cooperate, but by itself Axin2 is a very potent inhibitor of Wnt signaling that doesnt need activation.

Dave Dyck

My interests lie in the regulation of fat and carbohydrate metabolism in skeletal muscle, with a particular emphasis on the dysregulation that occurs in obesity and diabetes. Several cytokines released from skeletal muscle, including leptin and adiponectin, are known to significantly affect insulin response in peripheral tissues such as muscle. My research has focused on the effects of these adipokines on muscle lipid and carbohydrate metabolism, and particularly, how the muscle becomes resistant to their effects in obese models and with high fat feeding. The interaction of diet and exercise is also a point of interest in terms of the muscle's response to various hormones including insulin, leptin and adiponectin.

Jaideep Mathur

Our lab works on three major areas of plant biology:
1) Cytoskeleton & Cell Morphogenesis: We study the pivotal role played by the cytoskeleton in cell shape development in higher plants.
2) Live Cell Visualization & Organelle Dynamics: We are presently dissecting the response hierarchy and localized co-operation between plastids, mitochondria and peroxisomes and also between the actin and microtubule components of the cytoskeleton during differential growth in higher plant cells.
3) Plant Interactions: We are using different live-cell probes and a collection of Arabidopsis mutants to document the earliest intracellular responses of plant cells to diverse environmental stimuli.

Rod Merrill

My research is in the general area of protein structure and dynamics and is specifically focused on the biochemistry of bacterial toxins involved in disease and consists of the following projects: Membrane structure of the colicin E1 ion channel; data mining and bioinformatics of bacterial virulence factors; optical spectroscopic approaches to study protein structure and dynamics; enzyme reaction mechanism of the bacterial mono-ADP-ribosyltransferase family; inhibition mechanisms and structural complexes of toxins with inhibitors; and, X-ray structures of protein-protein complexes involving toxins.

Lorraine Jadeski

Ray Lu

My lab focuses on two main axes of research:
1) Unfolded Protein Response and Human Diseases: We study proteins that play key roles in animal stress responses, specifically the Unfolded Protein Response (UPR) that is caused by stress in the endoplasmic reticulum. The UPR has been linked to animal development, cell differentiation, as well as a variety of human diseases such as Alzheimers, diabetes, cancer and viral infection. Specifically, we look at: stress signaling mediated by these proteins (their upstream and downstream targets), and how it is related to cellular processes or animal diseases (lipid metabolism/obesity, hypoxia/cancer, glucose metabolism/diabetes, and inflammation); the molecular mechanism of how these genes/proteins are regulated during the stress response (e.g., transcriptional regulation, protein translational modification and trafficking etc).
2) Molecular Mechanisms of Aging: We are working to establish planarians as a new aging model to test the hypothesis that longevity requires multiplex resistance to stress. We hope to identify genes or alleles that confer such multiplex stress resistance and/or promote longevity.

Robert Mullen

My research focuses on three main areas of plant cell biology:
1) Characterization of enzymes involved in seed oil biosynthesis: This research is aimed at understanding various aspects of the molecular and cellular mechanisms involved in producing seed oils and their proper packaging into oil bodies. One of our current goals is to engineer neutral lipid accumulation in vegetative tissues of plants.
2) Understanding various aspects of the biogenesis of peroxisomes, including how membrane proteins are targeted to this organelle, and what role the endoplasmic reticulum (ER) serves in the formation of peroxisomes. We are also especially interested in understanding how certain viruses "hijack" peroxisomes for their replication in infected plant cells.
3) Identification and characterization of a unique class of integral membrane proteins known as "Tail-Anchored" (TA) proteins. Our research is currently aimed at identifying TA proteins using bioinformatic approaches and characterizing these proteins in terms of their localization, targeting signals, and the protein machinery (e.g., receptors) that mediate their membrane insertion and assembly.

Leah Bent

The primary goals of my research program are 1) to understand where posture is controlled 2) to understand what sensory information contributes to successful movement and equilibrium.
By investigating these two key questions I believe we will have a better understanding of how sensory decline contributes to a loss of mobility as we age. Declines in sensory information are often replaced by other sensory modalities through compensation. Does this take place at the level of the spinal cord, or further upstream with changes in cortical plasticity? Are we able to develop facilitatory devices such as shoe insoles to improve cutaneous sensation or visual aids to enhance visual cues?
My research program involves two key areas of study:
1) To perform direct recordings from sensory afferents and motor efferents in awake human subjects to investigate sensory contributions to movement, balance control, and reflex responses.
2) To elicit balance perturbations to test the function of these reflex loops, and sensory contributions to the maintenance of equilibrium and postural control.

Clara Cho

The primary goals of our research program include: 1) to determine the fundamental role of methyl nutrients in health outcomes; 2) to determine molecular mechanisms underlying the development of obesity, metabolic syndrome and chronic diseases; and, 3) to contribute to evidence-based strategies that will improve the health of the population.
Previous research contributions extend to the following:
1) Role of maternal intake of methyl vitamins in development of energy regulatory pathways.
2) Plasticity of hypothalamic development of food intake regulatory pathways.
3) Impact of diet and gut microbiome on trimethylamine-N-oxide production and metabolic fate in humans.
4) Mode of delivery and development of the immune system in the offspring.
5) Functional food strategies to control blood glucose and food intake in humans.

Jen Monk

My students and I aim to understand the mechanistic role(s) of microbial-host intestinal communication. In particular, we focus on how microbial-derived metabolites (from dietary precursors) can influence the integrity of the colonic epithelial barrier (EB), as well as its capacity for defense and repair. The importance of this research lies on not only advancing basic knowledge on the effect of microbial metabolites on gastrointestinal functions, but also on informing the agri-food sector the ways in which the intake of nutrients, biomolecules, and dietary precursors can shape human health.

Andrea Clark

More than 4 million Canadians have arthritis and the number of people living with arthritis continues to increase year after year. Arthritis is responsible for 6% of hospital admissions in Canada and costs Canadians over $6 billion/year in health care expenses and lost work days. Osteoarthritis can involve multiple tissues in a joint and often results in cartilage and meniscal damage, bone sclerosis and synovial inflammation. Current treatments, such as anti-inflammatory drugs, intraarticular steroid injections and joint replacement surgery, alleviate the symptoms (pain, compromised joint function) of osteoarthritis, but do not diminish its signs. A pressing need remains for joint localized therapies and interventions that could slow or ideally stop this debilitating disease.
The long-term objectives of my research program are to:
1) Identify and characterize signal transduction mechanisms through which chondrocytes detect and respond to mechanical and chemical changes in cartilage.
2) Advance our understanding of the molecular underpinnings of osteoarthritis.
In our research, we use genetic and surgical models of spontaneous osteoarthritis (with old age) and post-traumatic osteoarthritis (following injury). We harness confocal microscopy, histology, immunohistochemistry, reverse transcription polymerase chain reaction and micro-computed tomography technologies to follow the progression of osteoarthritis in a joint and to bring to light the mechanisms by which proteins such as TRPV4, integrin ?1?1 and cilia can influence chondrocyte signal transduction and thus the development of osteoarthritis. Through our studies of chondrocyte signal transduction and osteoarthritis we hope to identify novel approaches for improved treatments of this disease that will relieve the suffering of Canadians living with osteoarthritis.

Melanie Wills

My research group focuses on the diagnosis, prognosis and treatment of Lyme disease. I focus on different topics within this research theme, including: 1) the various forms that Borrelia (Lyme bacteria) can adopt and their corresponding role in the expression of the disease; 2) the effects of people and batceria genetics in the expression of of the disease; 3) the development of new diagnostic tools; and, 4) the interactions that people diagnosed with Lyme disease have with the medical system.

George van der Merwe

My lines of research include:
1) Adaptation to changing nutrient environments: We have identified an E3 ubiquitin ligase, the Vid30 or GID (Glucose Induced degradation Deficient) complex, as a novel component on the regulation of the transcriptomic and proteomic adaptation of yeast to changing nutrient conditions. Elucidating its mechanism of function in nutrient adaptation will not only increase our fundamental understanding metabolic regulation in eukaryotic cells, but also increase our understanding of the continuous nutrient depletion yeasts experience during fermentation.
2) Yeast domestication and fermentations: There are several aspects of yeast domestication that remain unresolved. Unraveling the origins and molecular underpinnings of domesticated traits will increase our understanding of yeast performance thereby developing strategies and predictions of fermentation efficiencies and flavour compound production during alcoholic fermentations (e.g. beer, cider, sparkling wine production).
3) Yeast diversity: wwWhile species of the genus Saccharomyces are commonly used in alcoholic fermentations, several non-Saccharomyces yeasts produce unique flavour compounds thereby adding flavour complexity and expanding product diversity in the wine, beer and cider industries. Understanding the contributions of these yeasts to flavour complexity will allow the development of strategies to increase product diversity in the beer and cider industries.

Graham Holloway

My research is primarily focused on understanding the regulation of mitochondrial bioenergetics, with a particular interest in studying fatty acid oxidation (breakdown of fat yielding energy) in skeletal and cardiac muscle. I use a variety of techniques to examine mitochondrial function (isolated mitochondria, permeabilized fibres, whole muscle incubations), use molecular biological approaches to up-and down-regulate mitochondrial proteins, as well exercise, altered nutrition and aerobic training to study novel regulation in mitochondrial bioenergetics. We apply basic knowledge garnered from these studies to the study of human exercise performance as well as type 2 diabetes, heart failure, diabetic cardiomyopathy and various neuropathologies, conditions that have all been affiliated with alterations in mitochondria as a key event in the progression and/or development of the disease.

Siavash Vahidi

A key focus of the group is on the protein degradation machinery that helps to maintain proper level of proteins (protein homeostasis) in Mycobacterium tuberculosis, the causative agent of TB, the world's single largest infectious killer that is annually responsible for 1.5 million deaths. Protein degradation in M. tuberculosis is partly handled by the proteasome machinery where the 20S proteasome core particle (the protease) collaborates with the mycobacterial proteasomal activator (Mpa, the unfoldase) to engage and destroy substrates in an ATP-dependant manner. M. tuberculosis relies heavily on robust proteasome function to survive the immune system of the host, rendering this mega-Dalton sized system an attractive drug target in the pharmaceutical industry. Several critical and outstanding questions remain that our group aims to answer:
1) What is the assembly mechanism of the M. tuberculosis proteasome core particle and its regulatory particles? What is the role of allostery and long-range interactions in the machinery that tags substrates for proteasomal degradation?
2) How are substrates selected for tagging and degradation?
3) What is the molecular basis of antibiotics that operate by disrupting proteasomal protein degradation?

Chris Whitfield

Research in my laboratory is focused on the architecture and assembly of the cell surfaces of pathogenic bacteria. Complex molecular machines coordinate the synthesis and export of cell-surface macromolecules and our goal is to understand their structure and function. This represents a fascinating challenge for experimental research and involves the application of a range of experimental strategies that span the disciplines of biochemistry, microbiology, molecular biology, and structural biology. The systems being investigated are of fundamental importance in understanding the physiology and pathogenesis of bacteria and they may yield new therapeutic strategies for intervention in bacterial infections.
Current areas of emphasis are:
1) Structure and function of multi-enzyme complexes required for the export of capsular polysaccharides through the periplasm and across the outer membrane of Gram-negative bacteria.
2) Structural basis for substrate recognition by ABC transporters involved in the export of bacterial cell-surface polysaccharides.
Structure and function studies of prokaryotic glycosyltransferase enzymes.
3) Mechanisms that couple glycan biosynthesis and chain extension to transport pathways.

John Vessey

Although my research could be described as cellular, molecular or developmental, at heart, Im a neuroscientist spanning all of those categories. My research focuses on asymmetric RNA localization and localized translational control. In hippocampal neurons, this process serves to deliver specific mRNAs to distal dendrites where they wait for the proper signal to undergo translation where the resulting proteins subsequently contribute to synaptic plasticity. While learning about the genes and proteins involved in this process, I discovered that in organisms such as fruit flies and frogs, asymmetric RNA localization also plays a role in asymmetric cell divisions in the stem cells of the developing nervous system. I have also studied asymmetric RNA localization in neural stem cells and their contribution to both cellular differentiation and cortical development across species. Currently, my students and I are investigating various proteins that we think are important for RNA regulation during brain development.

Annette Nassuth

My research group investigates biotic and abiotic stress on plants at the cellular and sub-cellular biochemical and molecular levels. The objective is to identify what changes occur in plant cells upon exposure to stress and which of these changes aid the plant to increase its tolerance to the stress.
A major focus currently is the investigation of freezing stress tolerance in grapevines. Winters in Ontario can cause substantial damage to the cultivated grapes used in the Wine Industry, whereas wild grapes have no problems. We try to find out what the molecular basis is for this phenomenon. In particular, what genes switch "on" or "off" and thereby regulate a large number of other genes? What is different between these genes in the freezing tolerant wild Vitis riparia and the freezing sensitive wine grape Vitis vinifera or other members of the Vitaceae family? Potentially interesting genes are analyzed by a variety of techniques, including bioinformatic analyses, RT-PCR to detect the type of transcripts and conditions under which they accumulate, and mutant plants. We have developed a quantitative transient transactivation assay which we use to analyze the regulating transcription factors we have identified. The ultimate goal is to use this knowledge to improve freezing and drought stress tolerance in the cultivated grapes.