Director of CSB
T. Martin Schmeing
Bellini Life Sciences Building, Room 457
Research interest: nonribosomal peptide synthetase, NRPS, X-ray crystallography, electron microscopy, antibiotics, green chemicals, chemical biology, macromolecular machine, protein structure, megaenzyme
Martin Schmeing is an Assistant Professor in the Department of Biochemistry and Associate Director of the CSB. His research program explores nonribosomal peptide synthetases (NRPSs), huge macromolecular machines that produce a vast variety of small molecules with diverse biological activity, including antibiotics, anti-virals, anti-cancers and immunosuppressants such as penicillin, gramicidin and cyclosporin. Dr. Schmeing uses structural and biochemical techniques to expand our understanding of how NRPS synthesize their bio-active products. He addresses topics ranging from the precise chemical mechanisms NRPSs use to link together building blocks and to release product, to the architecture and huge conformational changes required by NRPSs to processively synthesize important compounds. Full understanding of NRPSs will allow them to be bioengineered to create novel therapeutics and green chemicals.
Associate Director of CSB
Bellini Life Sciences Building, Room 470
Research interest: DNA repair, DNA mismatch repair, DNA replication, transposition, protein-DNA interactions, weak protein interactions, X-ray crystallography, small-angle X-ray scattering, electron microscopy
Our goal is to understand how proteins determine the fate of DNA during chromosome replication and repair. In particular, how regulatory proteins orchestrate the stabilization of damaged replication forks with DNA repair and forks restart. Since most of the proteins that regulate these processes lack a measurable enzymatic activity, our efforts are aimed at seeing how they work using a broad range of structural and biophysical techniques. We then combine structural information with biochemical and genetic analysis to elucidate their functions at a molecular level.
Albert M. Berghuis
Bellini 4th floor lab 470
Research interest: antibiotic resistance; drug development; enzyme mechanism; protein-drug interactions; protein engineering; structure-based drug design
Dr. Berghuis’ research focuses on exploiting various complementary biophysical techniques, such as X-ray diffraction, scattering and nuclear magnetic resonance spectroscopy, to examine the structural basis for enzyme mediated catalysis. Knowledge gained from these studies can subsequently be applied to the development of drugs, when the enzyme is implicated in disease. Alternatively, such information can inform protein-engineering efforts for green chemistry applications, if the enzyme catalyzes an industrial relevant chemical transformation. One of the main research directions pursued in Dr. Berghuis’ lab is the study of bacterial enzymes that provide protection to anti-infectives, thus conferring antibiotic resistance. This research has shed light on the origins of bacterial drug resistance, and more importantly, has informed the development of next-generation anti-infectives that are less susceptible to antibiotic resistance. In this context, Dr. Berghuis is also pursuing adjuvant therapy strategies by employing various structure-guided lead development approaches, such as fragment screening, with the objective of combating in antibiotic resistant infections.
Bellini Life Sciences Complex, Rm. 273
Research interest: cytoskeleton; microtubule; mitosis; neurons; cancer therapy; microtubule-associated protein; single molecule biophysics; cryo-electron microscopy
Cells of the human body adopt a range of shapes, from the pancake-flat skin cells of the inner cheek to the tree-like neurons of the hippocampus. How does a cell become a tree and not a pancake? The shape of a cell is determine by an underlying cellular skeleton, or cytoskeleton, just as the shape of a vertebrate’s body is determined by its bones. The Brouhard lab studies the “bones” of the cytoskeleton, polymers known as microtubules — how they are formed and how their formation changes a cell’s behavior. Cells can build an amazing variety of structures from microtubules, structures notable for their range of shapes, their ability to respond to stimulus, and their motility. Our scientific interests are in the biophysical mechanisms by which cells engineer these large-scale structures—in other words, the physical basis of cell shape and organization. Microtubules are prominent drug targets in cancer therapy and their misregulation underlies many brain diseases. The Brouhard lab uses biophysics, cell biology, and biochemistry to perform basic health science research that is oriented toward understanding and treating these diseases.
Khanh Huy Bui
3640 University, Room W309, Strathcona Anatomy Dentistry Building Montreal, Quebec H3A 0C7 Phone: 514-398- 4795
Research interest: Cilia, cytoskeleton, macromolecular complex, cryo-electron microscopy, cryo-electron tomography, correlative light-electron microscopy
Cilia are hair-like structures protruding out of the cell, taking part in a wide variety of biological processes. Since the cilia play an essential role in the development and function of the cell, cilia-related diseases usually have detrimental effects on the development and the health of patients such as retardation, blindness and chronic respiratory diseases. Understanding how cilia function, will provide opportunities to effectively diagnose and treat cilia-related diseases. Our research focuses on elucidating the three-dimensional structure of the cilia and the underlying logistic system used to dynamically maintain and assemble the cilia. We aim to obtain high resolutions of various components of the cilia by cryo-electron microscopy and cryo-electron tomography. Together with complementary data, we will model the atomic structures of cilia components to get novel insights into the molecular mechanism of ciliary assembly. In addition, we will also use correlative light and electron microscopy to exploring the ciliary dynamics.
Allen J Ehrlicher
Research interest: mechanobiology, motility, cytoskeleton, mechanotransduction, cell mechanics, rheology, traction forces, actin, biomimetic materials, metastasis.
Dr Ehrlicher’s research is focused on biological mechanics, developing diagnostic and therapeutic tools based on biophysical insight, and translating the design principles of biological mechanics into new biomimetic materials. Biological materials are unique in that they are able to convert chemical energy into active forces in precisely controlled ways. These active forces in biological interactions are as critical as the chemistry acting on biology, as can be seen in diverse examples from stem-cell differentiation to cancer metastasis. Dr Ehrlicher’s research focuses on the actin-cytoskeleton, a ubiquitous biopolymer structure that is largely responsible for cell structure and movement. Probing this system, Dr Ehrlicher’s research strives to understand 1) how the feedback loop of mechanics and biology regulates the properties of biological systems, drawing on challenges in diverse pathologies, and 2) how we may capitalize on these unique mechanics to engineer new synthetic active biomimetic materials.
Rm 469 Bellini, Life Science Complex
Research interest: NMR, X-ray crystallography, SAXS, Ubiquitin, Parkinson’s disease, Parkin, polyA binding protein, protein disulfide isomerase
Kalle Gehring, is the Director of the Quebec/Eastern Canada High Field NMR Facility (QANUC) and the founding Director of the FRQS-sponsored Groupe de Recherche Axé sur la Structure des Protéines. He also directs the NSERC CREATE training grant program in Bionanomachines. He brings experience in a broad range of biophysics and structural biology techniques. He trained at Berkeley and Paris and brings additional experience in X-ray crystallography and small-angle X-ray scattering (SAXS). His current research focus is the interdisciplinary application of biophysical techniques to studying diseases such as Parkinson's disease and cancer.
Institute of Parasitology
Research interest: Leishmania, peroxisome, membrane protein, Protein-protein interaction, Trichuris suis, Type III Secretion, Enteropathogenic E. coli,
The Jardim group employs biophysical, biochemical, genetic, and microscopic techniques to investigate three major research themes. These include; 1) the dissection of the protein- protein and protein-lipid interaction involved in the biogenesis of the glycosome, an organelle found in the parasite Leishmania, which is being validated as a target; 2) studying the assembly of the E. coli type III secretion system translocon on the host cell plasma membrane, and 3) the identification and immunological characterization of immunomodulatory proteins and metabolites released by the parasitic worm Trichuris suis; factors that are being investigated in the treatment of autoimmune disorders.
Pulp & Paper 301
Research interest: Protein and Nucleic Acid Dynamics, Allostery, Enzyme Catalysis, Drug Design, Nuclear Magnetic Resonance Spectroscopy, Isothermal Titration Calorimetry, Differential Scanning Calorimetry
Research in the Mittermaier lab is focused on understanding protein and nucleic acid function at the atomic level. We combine the site-specific information on macromolecular motions that can be gained from high-field solution state NMR spectroscopy with the detailed thermodynamic information yielded by calorimetry and other biophysical techniques. We apply this combined approach to elucidate the mechanisms underlying a variety of fundamental biological phenomena including folding, catalysis, and allostery, with applications to drug design, protein and nucleic acid engineering, and biologics development.
Bellini Life Sciences Complex 3649 Prom. Sir-William- Osler, Room 168 Montreal, QC, H3G 0B1
Research interest: Neurodegeneration, Alzheimer disease, amyloid, amyloid precursor protein, amyloid toxicity, amyloid clearance, secretases, biomarkers, metal-ion binding proteins, targeted proteomics
My research activities cover structural and functional aspects of key proteins involved in Alzheimer disease (AD) and other disorders to find new preventive, diagnostic and therapeutic approaches for the treatment of neurodegenerative diseases.
Life Sciences Complex, Bellini Building Room 456
Research interest: innate immunity, RNA Silencing, signalling, protein kinases, translation initiation, X-ray crystallography, small-angle X-ray scattering
Our lab uses X-ray crystallography, SAXS and other biophysical techniques to probe the molecular basis for how macromolecules mediate important biological processes. The specific biological areas we are interested in are innate immunity and RNA silencing. With regards to innate immunity we study how host receptors specifically engage molecular patterns found on pathogens and how this recognition activates host defense mechanisms. In RNA silencing we are interested in determining the molecular details of miRNA biogenesis and how this leads to gene silencing.
Strathcona Anatomy Building. Room W315B
Research interest: cryo-electron microscopy, antimicrobials, antibiotiotics, ribosomes, single particle analysis
Ribosomes are responsible for the process of decoding mRNA into proteins, a process essential to sustain life. Bacteria with defects in ribosome biogenesis exhibit slower growth and severely reduced ability to cause disease. Ribosomes are arguably the most complex molecular nanomachines in the cell. They are comprised of a small (30S) and a large (50S) subunit and overall they contain over 50 different components. In recent years, extraordinary efforts in structural biology have provided atomic structures of the ribosome generating a detailed three-dimensional view of the process of protein synthesis and how antibiotics currently used in the clinic function by targeting the mature ribosome. These structures have been essential to both find new antibiotics as well as to make existing ones more powerful. However, atomic resolution structures of ribosome assembly intermediates have not been obtained and the present structural understanding of the intricate process of assembly of the ribosome is very superficial. This void of knowledge limits our ability to develop new antibiotics targeting the process of ribosome assembly. Our laboratory uses cryo-EM to obtain atomic resolution structures of ribosome assembly intermediates and visualize in 3D the complexity of this process. Structural biology techniques have been instrumental in the discovery of antibiotics targeting the mature ribosome. The atomic resolution structures of immature ribosomes obtained in our laboratory are having the same impact and are providing an extensive reservoir for the discovery of new antibiotics that target ribosome assembly.
Strathcona Anatomy & Dentistry Building
Dr. Rouiller’s research focuses on understanding the mechanisms used by proteins to cross cellular membranes using high resolution molecular cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET). She studies the motor protein p97 and its role in health and disease. Additional research projects examine several macromolecular structures and biological assemblies involved in polyomavirus, anthrax toxin function and ER-associated protein degradation.
Bellini Rm 170 / McIntyre Rm 1126
Research interest: Cardiac electrophysiology, cardiac dynamics, potassium channels, TRP channels, trafficking, arrhythmias,
The Shrier lab is interested in ion channel function and cardiac dynamics. We study the molecular mechanisms that underlie the quality control and regulation of hERG and TRPM7 channels, respectively. We also use optical dyes to image the conduction of the cardiac impulse in patterned cultured cardiac myocytes that we analyze and model using nonlinear mathematical techniques. The aim is to understand the origin and termination of abnormal rhythms that occur in the heart and other excitable systems.
McIntyre Medical Building, Room 815
Research interest: lipids, membranes, microdomains, endocytosis, lipid rafts, lipidated signaling proteins, intracellular targeting, intracellular transport, Ras
John Silvius is a Professor in the Department of Biochemistry. His research interests are focused on understanding two important aspects of the targeting, and hence the function, of proteins involved in signal transduction at the plasma membrane: (1) understanding the organization and function of the specialized membrane microdomains known as lipidrafts; (2) elucidating the mechanisms of targeting of lipidated signaling proteins to their correct subcellular destinations. Silvius is an internationally recognized expert in protein intracellular targeting, transport and the signaling functions of Ras oncoproteins.
Department of Pharmacology & Therapeutics, McIntyre Building room 1313
Research interest: Parkinson’s disease, mitochondria, Parkin, PINK1, ubiquitin, X-ray crystallography, NMR, SAXS, mass spectrometry
My research interests are in the structure and function of proteins implicated in Parkinson’s disease, Parkin and PINK1 in particular. My goal is to understand how these proteins protect neurons, and how they are inactivated in PD. These proteins have been shown to mediate mitochondrial quality control through their enzymatic activities and post-translational modifications: PINK1 phosphorylates ubiquitin, which in turn switches on Parkin’s E3 ubiquitin ligase activity. My objectives are to: 1) elucidate their mechanism of action through structural studies 2) develop novel therapies for PD based on these structures. My approach consists of deciphering the code of these proteins through the elucidation of their structures using a wide-range of sophisticated techniques such as X-ray crystallography, nuclear magnetic resonance and mass spectrometry. These structures can be used as scaffolds for designing new drugs that will enhance their activity and therefore could help slow down or even stop the degeneration of neurons causing PD.
Youla S. Tsantrizos
Otto Maass Chemistry Building, room 300
Research interest: Structure-based design and synthesis of molecular tools that can be used to probe the function of biological targets
Our program centers on the design and synthesis of molecular tools that can be used to probe biochemical pathways implicated in human diseases. We are currently investigating four biological targets: the human 1. farnesyl pyrophosphate synthase (hFPPS), 2. geranylgeranyl pyrophosphate synthase (hGGPPS) and 3. metalloproteinase ZMPSTE24, and 4. the HIV-1 reverse transcriptase (RT). Under the large umbrella of each of these projects, the following three objectives summarize the main scope of research efforts: (a) Implementation of structure-based screening methods that probe protein/ligand interactions; (b) Development of synthetic methodologies amenable to enatioselective synthesis of structurally diverse heterocyclic and peptidomimetic ligands; (c) Development of reliable structural and functional assays for guiding structure-activity relationship (SAR) studies. Our studies are truly multidisciplinary and involve a seamless integration of synthetic organic chemistry, structural research and biochemistry.
Paul W. Wiseman
McGill University Department of Chemistry Otto Maass (OM) Chemistry Building 801 Sherbrooke Street West Room 330 Montreal, Quebec, Canada H3A 0B8
Research interest: Biophysical Chemistry, Biophysics, Image Correlation Spectroscopy, Image Cross-Correlation Spectroscopy, Fluorescence Microscopy, Multiphoton Microscopy, Cell Migration, Cell Adhesion, Cell Transport, Oligomerization
Development and cellular applications of imaging based fluorescence fluctuation methods including image correlation spectroscopy (ICS), moment analysis, and spatial intensity distribution analysis (SpIDA) to measure receptor transport, densities, and oligomerization state within intact cells. Characterization of cellular signaling, receptor transport and protein interactions in living cells and neurons with application to cell migration, signal transduction, axon pathfinding and synaptic formation. Application of new nonlinear microscopy techniques for imaging extracellular matrices and metallic nanoparticles, and detecting malaria infected blood cells.
Yu (Brandon) Xia
Macdonald Engineering Building, Room 389
Research interest: computational biology, bioinformatics, structural biology, systems biology, network biology, molecular evolution, biomolecular engineering
Dr. Xia’s research focuses on computational biology and bioinformatics. The research goal is to construct genome-scale computer models of biomolecular networks with high spatial and temporal resolutions, and to use these genome-scale models to probe design principles of biological networks, and to study systems biology of disease. Current research activities include: (1) computational structural biology, focusing on the prediction and analysis of protein structure and function, and the elucidation of evolutionary design principles of proteins; (2) computational systems biology, focusing on the prediction and analysis of protein networks, and the elucidation of evolutionary design principles of protein networks; (3) bioinformatics, focusing on the development and application of bioinformatics algorithms to analyze biological sequence, structural, and functional data.
Jason C. Young
Bellini Building, Room 457
Research interest: chaperones, heat shock proteins, protein folding, protein degradation, intracellular trafficking, endoplasmic reticulum, protein misfolding diseases
Protein misfolding underlies many diseases. These include genetic diseases of ion channels such as CFTR in cystic fibrosis and hERG in long QT syndrome, but neurodegeneration and cancer. My research studies the molecular chaperones, which are key factors in cellular protein folding and quality control. We aim to understand how the biochemical mechanisms of the major chaperone Hsp70 and its regulatory co-chaperones underlie their cellular functions. A central idea is that the co-chaperones determine the specificity of Hsp70 function. Using a combination of cell biology and pure protein biochemistry, we are addressing how the Hsp70 system controls the balance between folding, trafficking and proteasomal degradation of misfolded ion channels and other proteins. Also, we are investigating the molecular mechanisms of protein refolding and disaggregation by Hsp70, and its potential as a therapeutic drug target in certain cancers.
Department of Chemistry, Member of the Centre for Self-Assembled Chemical Structures.
He specializes in the use of smart fluorescent probes for cell-imaging and single-molecule fluorescence to study the interactions between protein, DNA and lipids.
Department of Chemistry
He is interested in synthesis, biochemical properties and molecular behavior of nucleic acids (DNA, RNA) and their analogues. His research aims for detailed understanding of communication between nucleic acids, and between nucleic acids and proteins.
School of Computer Science, Director of the McGill Centre for Bioinformatics.
He uses tools from statistical inference and algorithm design to address problems arising in biological and medical research. His research currently focuses on breast cancer, the endoplasmic reticulum interactome and cystic/pulmonary fibrosis.
Department of Physics.
She develops and applies new physical instrumentation to generate new mechanistic insights into a wide range of cellular processes. She is inventing and implementing new single-molecule microscopy tools to visualize fast molecular searches, with a current focus on DNA repair in yeast.
Department of Physiology.
His long-term goal is to elucidate the molecular and cellular basis of cystic fibrosis caused by mutations interfering with the folding, stability, activity and/or membrane trafficking of the channel. His laboratory also works on the structural and biochemical basis of ubiquitin recognition as an endocytic and postendocytic sorting signal.
Marc D. McKee
Faculty of Dentistry.
McKee’s research is focused on calcification of extracellular matrices in bones and teeth, and elsewhere, such as in the inner-ear otoconia and eggshells. He is investigating the role of mineral-binding proteins in normal and pathologic mineralization, as in urolithiasis (kidney stones), arthritis and vascular calcification (including atherosclerosis).
Dan V. Nicolau
Department of Bioengineering.
His research and teaching interests focus on the new discipline of Biological Engineering, in particular the intersection between nano- bio- and information technologies. Nicolau’s group works on the design and fabrication of dynamic hybrid nanodevices, including those based on molecular motors; single molecule diagnostic devices fabricated by semiconductor micro- and nano-fabrication; and the study of the “intelligent” behavior of microorganisms in microfluidic networks.
Department of Chemistry.
Her research involves using DNA to build nanostructures for medicine and materials science. This research will lead to the development of new drug delivery systems, diagnostic tools and cellular probes that could be used for prevention and treatment of disease. Her projects lie at the interface between synthetic chemistry, biological chemistry and materials science. They provide students with extensive training in small molecule synthesis, DNA and polymer chemistry, and molecular recognition and drug design.
Department of Biochemistry.
He researches the control and mechanisms of translation in normal and neoplastic cells.
David Y. Thomas
Department of Biochemistry.
His research examines the signal transduction pathways and folding mechanisms employed by cell proteins, which are targets for new disease therapies.
School of Computer Science.
His group works in the computational structural biology area, broadly defined. He develops theoretical models and algorithms to decipher the relationship between RNA and protein sequences and structures. In Waldispühl’s research, predicting molecular structures is not an end in itself, but a means to understand the genetic code and biological systems.