Department: Molecular and Cellular Biology

Scott Ryan

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While animal models have lead to huge advancements in our understanding of neurobiology, there is controversy over whether overexpression/silencing of gene expression is representative of diverse disease states. Indeed, the lack of availability of primary human neurons has made evaluating the pathological consequences of genomic mutations arduous. The use of human induced pluripotent stem cell (hiPSC) technology overcomes these limitations by providing a source of human neurons from both normal and disease genetic backgrounds. We currently focus on stem cell based models of Parkinson's Disease (PD) to study how mitochondrial stress mechanisms impact on neuronal function in human disease.

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Ian Tetlow

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My lab examines the control mechanisms underpinning starch biosynthesis in leaf chloroplasts (which make starch during the daytime, and degrade it at night) of the model plant Arabidopsis thaliana, and non-photosynthetic amyloplasts of cereal endosperms such as maize, wheat, barley and rice which make storage starches. More specifically, we are interested in the biochemical control mechanisms governing the many enzymes and enzyme classes which make up the core pathway of starch biosynthesis. This involves investigating the role of protein-protein interactions and protein phosphorylation in coordinating the proteins involved in starch synthesis and degradation within the plastid to produce the highly ordered and complex structure of the starch granule.

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Shaun Sanders

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The Sanders lab is interested in how neurons use the protein-lipid modification palmitoylation to target proteins to subcellular locations and to define how palmitoylation-dependent targeting contributes to physiological neuronal function and neuropathological conditions. Current projects include characterizing how palmitoylation of vesicular transport machinery regulates fast axonal transport and how palmitoylation of ion channels and their scaffold proteins regulates clustering at the axon initial segment, a critical site of neuronal excitability where action potentials are generated.

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Rebecca Shapiro

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To better study the biology and virulence of fungal pathogens, we are developing new genomic technology platforms for diverse fungal species. We are exploiting CRISPR-Cas9 based technologies to revolutionize the way we do high-throughput functional genomic analysis in fungal pathogens. This is enabling us to map large-scale genetic interaction networks, and uncover genetic factors and pathways that mediate important phenotypes associated with pathogenesis, antifungal drug resistance, and other biological processes associated with fungal infectious diseases.

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Krassimir Yankulov

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We use the budding yeast S.cerevisiae as a model organism to ask how established chromatin structure is preserved or changed during repetitive rounds of DNA replication, and how these structures are transmitted to daughter cells. We study the activity of chromatin factors that are highly conserved in all eukaryotes. Our specific focus is on cell-to-cell variations in gene expression. Most of these variations are mediated by chromatin. We know little about the mechanisms that confer these changes.

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Matthew Kimber

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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.

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Jasmin Lalonde

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The growth of neurons and their organization into circuits is a tightly controlled process that follows a series of well-defined steps. Once differentiated and integrated into networks, neurons also retain a remarkable capacity to rapidly change the arrangement of their connections in response to activity, a feature that is believed to critically support cognition as well as our ability to learn and retain information for long periods of time. Accumulating evidence strongly suggests that perturbation of the molecular interactions responsible for the growth of neurons, or the capacity of these cells to adequately respond to activity-dependent signals, contributes to the pathophysiology of different brain disorders. Our laboratory uses a multidisciplinary approach to explore these questions.

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Cezar Khursigara

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Dr. Cezar Khursigara's research focuses on understanding how bacterial pathogens respond to their environment to cause disease. They are particularly interested in factors involved in biofilm formation and chronic infection. His research group is taking a multidisciplinary approach to answer fundamental questions related to how bacteria form biofilms to cause persistent infections. By combining advanced systems biology and imaging techniques, his goal is to identify potential therapeutics that can target a broad spectrum of disease-causing bacteria.

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Stephen Seah

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We are interested in microbial enzymes involved in the steroid and aromatic compounds degradation. These enzymes are important for bioremediation of organic pollutants and are potential targets for development of antibiotics against tuberculosis. In collaboration with Dr. Ting Zhou at Agriculture Agri-food Canada, we are isolating and characterizing enzymes capable of detoxifying the mycotoxins, deoxynivalenol and patulin. These mycotoxins contaminate grains and fruit juices.

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Jim Uniacke

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Protein synthesis involves the translation of ribonucleic acid information into proteins, the building blocks of life. The initial step of protein synthesis consists of the eukaryotic translation initiation factor 4E (eIF4E) binding to the 5' cap of mRNAs. However, many cellular stresses repress cap-dependent translation to conserve energy by sequestering eIF4E. This raises a fundamental question in biology as to how proteins are synthesized during periods of cellular stress and eIF4E inhibition. Research in our laboratory will build upon the discovery that cells switch to an alternative cap-binding protein, eIF4E2, to synthesize the bulk of their proteins during periods of oxygen scarcity (hypoxia).

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Jennifer Geddes-McAlister

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We are interested in characterizing the mechanisms of pathogenesis, adaptation, and survival in fungal and bacterial microbes from a systems biology perspective through mass spectrometry-based quantitative proteomics. Specifically, research in the lab centres around the following areas:
1) Systems biology to elucidate microbial proteome dynamics and interactions;
2) Mechanistic characterization of pathogenic proteins; and
3) Mass spectrometry-based proteomics for drug discovery and repurposing.

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Georgina Cox

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The Cox lab aims to gain a better understanding of the molecular underpinnings of resistance mechanisms. Specifically, we study bacterial efflux systems, which will provide insight into their physiological functions and origins and will also support future drug discovery efforts and antibiotic stewardship. In addition, recognizing the need for innovation in the search for new antibacterial agents, we are exploring novel approaches to control bacterial infections by investigating the inhibition of bacterial adhesion to host cells.

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Steffen Graether

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The main goal of our research program is to understand how the intrinsically disordered late embryogenesis abundant (LEA) proteins are able to protect plants from damage caused by cold, drought and high salinity. Our main focus has been on dehydrins, a group of abiotic stress response proteins that have been shown to protect plants from damage caused by drought and cold. Dehydrins are interesting in that they are composed of a variable number of conserved motifs that appear to have roles in protection of proteins, membranes and DNA from abiotic damage, as well as roles in localization.

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John F. Dawson

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Prof. Dawson studies the impact of inherited changes in heart muscle proteins to understand what is going wrong in patients with heart diseases so that we can develop specific strategies to treat the problem. His research takes the research from molecules to organisms, studying the biochemistry of proteins and the development and physiology of zebrafish with changes in their hearts reflecting those seen in people with diseases.
Prof. Dawson's education research focuses on learning outcome assessment in general and the development, implementation, and assessment of critical thinking through higher education science curricula in particular.

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Wei Zhang

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First, we have systematically generated inhibitors and activators for E3 ubiquitin ligases to discover new enzyme catalytic mechanism and new substrates. We continue to develop synthetic peptides and proteins to delineate biochemical mechanisms of E3 ubiquitin ligases.
Second, we showed that structure-based protein engineering enables development of anti-viral reagents for Middle East respiratory syndrome (MERS) coronavirus. Now we started engineering post-translational modifications to probe and rewire DNA damage signaling for cancer therapeutics.
Finally, we created molecular tools to increase CRISPR-Cas9 genome-editing efficiency. Now we are developing new tools as "off-switch" for CRISPR-based gene editing through targeted protein degradation.

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