We are interested in understanding how mast cells recognize beneficial and pathogenic microbes to maintain tissue homeostasis and educate the immune system. Our lab uses an interdisciplinary approach that combines mouse and microbial genetics, receptor pharmacology, sequencing, multiparameter flow cytometry, microscopy, and infection models to elucidate how the G protein-coupled receptors expressed by mast cells act as sensors of the communication between host and microbes. Our ultimate goal is to guide fundamental knowledge necessary for developing next-generation therapeutics for infectious and inflammatory diseases.Learn More
Department: Molecular and Cellular Biology
The Alpaugh Lab studies the mechanisms and consequences of protein misfolding in neurodegenerative diseases.
Theme 1- Interactions between the blood-brain barrier and misfolded proteins. Protein accumulation and blood-brain barrier break down are common features of diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases. We aim to understand if these two common disease features are related using a human 3D-cell culture model of the blood-brain barrier and human tissue.
Theme 2- Contributions of huntingtin seeding and spreading to Huntington’s disease. The mutant huntingtin protein displays prion-like properties. The Alpaugh lab is tackling the relevance to Huntington’s disease using tissue from human patients with Huntington’s disease phenocopies and Huntington’s disease.
Research in the Xu laboratory focuses on plant and microalgal lipid metabolism. By applying state-of-the-art approaches in genetics, biochemistry, cellular biology, synthetic biology and biotechnology, we aim to address both fundamental and applied questions in the field. The major research objectives in our research group are to improve our understanding of the mechanisms underlying acyl lipid assembly (e.g. triacylglycerols/oils, galactolipids/photosynthetic membrane lipids, phospholipids/membrane lipids) in photosynthetic organisms and to design lipid biosynthetic pathways to improve agriculture production and produce value-added oils for food, feed, fuel, and materials applications.Learn More
Healthy gut microbiota can be disrupted due to antibiotic treatment, intestinal inflammation, or changes in diet. Targeted restoration of the microbiota will require an understanding of how genomic diversity between closely related microbes influences their ability to drive beneficial functions. To address this, our laboratory will use a large collection of whole-genome sequenced isolates to understand how variation between closely related gut isolates alters their ability to prevent pathogen expansion and maintain homeostatic interactions with the mucosal immune system.Learn More
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. The questions we aim to answer are:
1) What is the assembly mechanism of the M. tuberculosis proteasome core particle and its regulatory particles?
2) What is the role of allostery and long-range interactions in the machinery that tags substrates for proteasomal degradation?
3) How are substrates selected for tagging and degradation?
4) What is the molecular basis of antibiotics that operate by disrupting proteasomal protein degradation?
We study the transcriptomic and proteomic adaptation of yeasts to changing nutrient environments, as well as their domestication and fermentation to better understand yeast performance and potentially develop strategies and predictions of fermentation efficiencies and flavour compound production during alcoholic fermentations. We also look at yeast diversity and the unique flavour compounds that could expand product diversity in the wine, beer and cider industries.Learn More
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.Learn More
My research focuses on asymmetric RNA localization and localized translational control in animal species. 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.Learn More
Research in my laboratory is focused on the architecture and assembly of the cell surfaces of pathogenic bacteria. 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.
3) Structure and function studies of prokaryotic glycosyltransferase enzymes.
4) Mechanisms that couple glycan biosynthesis and chain extension to transport pathways.
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 bacteria 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.Learn More
The ultimate goal of my research is to understand viruses and viral diseases for the betterment of agriculture. 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 polyproteins; structure and cellular localization of viral replication complexes; evolution and bio-informatics of grapevine viruses; development of virus-induced gene-silencing vectors ; and, development and application of technologies for the diagnosis of grapevine viruses.Learn More
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. The ultimate goal is to use this knowledge to improve freezing and drought stress tolerance in the cultivated grapes.Learn More
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), which has been linked to animal development, cell differentiation, as well as a variety of human diseases such as Alzheimer’s, diabetes, cancer and viral infection.
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.
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 dissect 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 document the earliest intracellular responses of plant cells to diverse environmental stimuli.
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.Learn More
My research focuses on three main areas of plant cell biology:
1) Characterization of enzymes involved in seed oil biosynthesis.
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.
3) Identification and characterization of a unique class of integral membrane proteins known as "Tail-Anchored" (TA) proteins.
My primary research interest concerns the splendid array of compounds that are made by plants and the underlying molecular and biochemical basis of their synthesis. My lab focuses on natural products that are of medicinal, industrial or pharmacological relevance and on specialized metabolites that help plants cope with their dynamic environment. As an example, we investigate the biosynthesis, composition and structure of plant-derived polyisoprenoids. We also work closely with collaborators in various fields such as organic chemistry, food science, neurobiology, and ecology with the overall goal to shed light on the processes that operate at the interface of plant primary and secondary metabolism.Learn More
My lab aims to understand 1) the molecular genetic mechanisms of recombination in mammalian cells; 2) how defects in recombination contribute to tumorigenesis; and, 3) the nature of recombination hotspots. We are presently researching questions pertaining to: the mechanism and frequency of recombination in mammalian cells; the role of large palindromes in promoting recombination; mammalian heteroduplex DNA formation and repair; genetics of strand invasion and 3' end polymerization; how DNA sequences act to stimulate recombination; non-crossover mechanisms of homologous recombination; the genetic control of recombination.Learn More
As they are literally rooted in place, plants possess remarkable mechanisms that perceive, interpret, and respond to internal and external cues so as to optimise plant growth and development relative to prevailing environment conditions. Despite the incredible diversity in plant forms, the molecular mechanisms that control plant responses to internal and external cues are highly conserved across diverse genera. The timing and localisation of these mechanisms shape plant and development. Our research team aims to gain greater insights into molecular mechanisms that plants employ to convert internal cues and external signals into appropriate adjustments in resource acquisition and allocation, focusing on the role of gene regulation in conditioning these adjustments.Learn More
One of the fundamental questions in plant biology concerns the nature of the signals that bring about the transition from vegetative to reproductive growth. My research is aimed at characterizing the developmental signals that cause plants to flower. The primary focus of this work is the maize indeterminate gene (id1). Maize plants that lack id1 function flower extremely late, or not at all, and they exhibit abnormal flower development. The ID1 protein contains zinc-finger motifs, suggesting that it regulates the expression of other genes. Expression analysis reveals that id1 mRNA is expressed only in leaf tissue, suggesting that ID1 acts by controlling the production of leaf-derived signals that mediate the transition to flowering.Learn More
Cell adhesion and migration are fundamentally important to the existence of multicellular organisms. This is obvious in light of the numerous diseases that can afflict humans when these processes are impaired. Disruption of normal cellular adhesive and migratory activities can lead to developmental disorders and contribute to the progression of arthritis, immunological deficiencies and cancer. Both cell adhesion and migration are complex processes involving numerous biochemical signalling events, reorganization of the cellular cytoskeleton and localized remodelling of the plasma membrane. It is the goal of my laboratory to elucidate the molecular mechanisms that link these activities, allowing them to be coordinated during changes in cell adhesion and motility.Learn More
Much of our current effort is focused on understanding the regulation of starch synthesis in storage tissues such as the developing seeds of cereals. Starch is the major determinant of yield in such crops, and has wide application in both the food and non-food industries, yet there remain a huge number of unknowns in what limits the production and structure of this important glucan polymer. There is also an increasing realization that different types of starch provide benefits for human health. Our research covers cereals such as maize, barley, rice, and wheat, as well as the model organism Arabidopsis thaliana. I lead a large, interdisciplinary team whose expertise includes plant biochemistry, genetics, molecular biology, microbiology, human physiology, and nutrition.Learn More
Research in our laboratory is focused on defining eukaryotic signal transduction pathways, and investigating how mutations in components of these pathways can contribute to human disease. Signal transduction is a central process in multicellular organisms that allows for the exchange of informational cues between and within cells. Current areas of research include: 1) Signalling pathways controlling kidney podocyte morphology; 2) focal adhesion dynamics in cancer cells; and, 3) characterization of a novel neuronal adaptor protein, ShcD.Learn More
For bacteria, survival requires evading detection. Pathogens must evade their host, but all bacteria need to avoid being targeted by phages. Gram negative bacteria’s survival depends on lipopolysaccharide and capsule – highly complex carbohydrate molecules that coat their outer surface. The enzymes that produce these molecules are complex, drawing on a large set of basic modules but then tweaking and combining them into new organizations that accomplish unique ends. My lab is focused on understanding how the structures and large-scale architectures of these enzymes create the enormous variety of unique custom carbohydrates observed in nature. To this end, we use crystallography, enzymology, and a variety of biophysical assays and bioinformatics tools to better understand these proteins.Learn More