Members

T. Martin Schmeing

Martin Schmeing is an Associate Professor in the Department of Biochemistry and 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 bioactive 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.

Alba Guarné

Dr. Guarné’s goal is to understand how proteins determine the fate of DNA during chromosome replication and repair. She investigates 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, efforts are aimed at seeing how they work using a broad range of structural and biophysical techniques. Combining structural information with biochemical and genetic analysis elucidates their functions at a molecular level.

Karine Auclair

Dr. Auclair’s research work takes advantage of chemical tools to study and manipulate biological systems. She is especially interested in antibiotic resistance, enzymology and biocatalysis (towards green chemistry). Her research group has expertise in synthesis, medicinal chemistry, enzymology, mechanoenzymatic processes, biocatalysis, as well as protein purification, expression and engineering (including bioconjugation). The main goal of her research is to understand how enzymes work and how they can be harnessed or perturbed, especially for pharmaceutically relevant proteins such as antibiotic targets, resistance-causing enzymes, drug activation and drug metabolism. Results of these studies have implications in fields as varied as medicine, biotechnology, industrial processing, agriculture and food science.

Susanne Bechstedt

Dr. Bechstedt is interested in the control of microtubule dynamics by microtubule associated proteins (MAPs). Microtubules within cytoskeletal structures, like mitotic spindles, are not very long-lived. Despite appearing as solid and stable and their ability to exert large forces, individual microtubules are constantly turning over with half-lives of about 20 seconds, while the entire spindle remains stable for minutes to hours.  This highly dynamic behavior is controlled by MAPs, many of which are associated with diseases like neurodegenerative disorders or cancer. The Bechstedt’s lab is using biophysics, cell biology, and structural biology to understand how MAPs are taking control of microtubules and what goes wrong in diseases.

Albert M. Berghuis

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 be applied to the development of drugs if the enzyme is implicated in disease. As well, such information can aid protein engineering efforts for green chemistry applications if the enzyme catalyzes an industrially relevant chemical transformation. One of the main research directions pursued in Dr. Berghuis’ lab is the study of bacterial enzymes that provide protection against 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, which are less susceptible to antibiotic resistance. In this context, Dr. Berghuis is also pursuing adjuvant therapy strategies by employing various structure-guided development approaches such as fragment screening, with the objective of combating antibiotic resistant infections.

Gary Brouhard

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. The lab’s 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 oriented toward understanding and treating these diseases.

Khanh Huy Bui

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 malfunction usually has 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. Dr. Huy Bui’s research focuses on elucidating the three-dimensional structure of the cilia and the underlying logistic system used to dynamically maintain and assemble the cilia. The lab aims to obtain high resolutions images of various components of the cilia by cryo-electron microscopy and cryo-electron tomography. Using complementary data, the lab models the atomic structures of cilia components to obtain novel insight into the molecular mechanism of ciliary assembly. In addition, they use correlative light and electron microscopy to explore the ciliary dynamics.

Gonzalo Cosa

Dr. Cosa specializes in the use of smart fluorescent probes for cell-imaging and single-molecule fluorescence to study the interactions between protein, DNA and lipids.

Masad Damha

Dr. Damha is interested in synthesis, biochemical properties and molecular behaviour 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.

Allen J Ehrlicher

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 to capitalize on these unique mechanics to engineer new synthetic active biomimetic materials.

Kalle Gehring

Kalle Gehring was the founding 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 directed 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 in 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 study diseases such as Parkinson’s and cancer.

Adam Hendricks

Armando Jardim

The Jardim group employs biophysical, biochemical, genetic, and microscopic techniques to investigate three major research themes. They are; 1) dissection of the protein-protein and protein-lipid interactions 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) identification and immunological characterization of immunomodulatory proteins and metabolites released by the parasitic worm Trichuris suis. These factors are being investigated for the treatment of autoimmune disorders.

Sabrina Leslie

Dr. Leslie 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.

Nathan Luedtke

Gergely Lukacs

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 bases of ubiquitin recognition as an endocytic and postendocytic sorting signal.

Maureen McKeague

Anthony Mittermaier

Research in the Mittermaier lab is focused on understanding protein and nucleic acid function at the atomic level. Researchers combine site-specific information on macromolecular motions gained from high-field solution state NMR spectroscopy with detailed thermodynamic information yielded by calorimetry and other biophysical techniques. This combined approach elucidates 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.

Gerhard Multhaup

Dr. Multhaup’s research activities cover structural and functional aspects of key proteins involved in Alzheimer’s disease (AD) and other disorders to find new preventive, diagnostic and therapeutic approaches for the treatment of neurodegenerative diseases.

Bhushan Nagar

The Nagar lab uses X-ray crystallography, SAXS and other biophysical techniques to probe the molecular basis for how macromolecules mediate important biological processes, specifically, innate immunity and RNA silencing. The lab’s innate immunity studies address how host receptors engage molecular patterns found on pathogens and how this recognition activates host defense mechanisms. In RNA silencing, Dr. Nagar works toward determining the molecular details of miRNA biogenesis and how this leads to gene silencing.

Joaquin Ortega

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 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, both to find new antibiotics and 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 the ability to develop new antibiotics targeting the process of ribosome assembly. Dr. Ortega’s 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 the Ortega laboratory are having the same impact and are providing an extensive reservoir for the discovery of new antibiotics that target ribosome assembly.

Jerry Pelletier

Rodrigo Reyes-Lamothe

The work in my lab aims to understand the composition, architecture and activity of molecular machines as they work in the cell. My research addresses the fact that the intracellular environment is too complex to be accurately reproduced in test tubes. Therefore, we develop and use advanced fluorescence microscopy techniques to quantify cellular activities in genetically tractable “simple” organisms. The focus of my team is the study of DNA replication, which is both the most active guardian against genetic mutations and the most frequent source of genomic instability. An incomplete understanding of the molecular machine that carries out DNA replication, the replisome, is a major impediment to understanding its role in health and disease.

Reza Salavati

My research aims to unravel the structure and dynamics of regulatory network that controls RNA processing and abundance at molecular/mechanistic level in important human parasites that can be exploited for developing novel chemotherapeutics.

Alvin Shrier

The Shrier lab is interested in ion channel function and cardiac dynamics, studying the molecular mechanisms that underlie the quality control and regulation of hERG and TRPM7 channels, respectively. Optical dyes are used to image the conduction of the cardiac impulse in patterned cultured cardiac myocytes, analyzed and modeled 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.

Hanadi Sleiman

Her research involves using DNA to build nanostructures for medicine and materials science. This research aims toward 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, molecular recognition and drug design.

Nahum Sonenberg

His research examines the control and mechanisms of translation in normal and neoplastic cells.

Mike Strauss

The Strauss lab uses biophysical approaches to investigate topics in picornavirus cell-entry and packaging, as well as microbial biofilms. Sometimes that means we need to develop new tools to answer the questions we have. Much of Dr. Strauss’ work is centered on cryo-electron microscopy, and in particular, electron tomography. Dr. Strauss is a member of the Department of Anatomy and Cell Biology, and is the Technical Director of FEMR.

Christopher J. Thibodeaux

My lab is engaged in research efforts aimed at combatting the problem of antimicrobial resistance which, if left unchecked, has been predicted to become one of the most serious public health threats to ever face the human race.  We take three general approaches to address this problem.  First, we study the detailed molecular mechanisms of enzymes that synthesize structurally complex antimicrobial compounds.  While our initial research focuses on the basic mechanistic principles of this process, our work may eventually inform rational approaches to engineer these catalytic systems for the production of novel antimicrobial compounds.  Second, we discover new, naturally occurring antimicrobial compounds by mining the vast genome sequence databases available in the post-genomic era.  Using our ever-increasing understanding of natural biosynthetic processes, we can rapidly identify novel biosynthetic pathways and manipulate the genes to produce the encoded antimicrobial compound.  This approach provides direct access to novel antimicrobial compounds that can potentially be developed as human therapeutics.  Finally, we investigate the mechanisms used by bacteria to establish infections in humans.  Specifically, we seek an understanding of how bacteria regulate the formation of biofilms using small molecule signaling and protein-protein interactions.  Many of the biomolecular interactions we study in this project represent potentially useful, yet unexplored targets for the development of novel antibacterial strategies.

David Y. Thomas

His research examines the signal transduction pathways and folding mechanisms employed by cell proteins, which are targets for new disease therapies

Jean-François Trempe

Dr. Trempe’s research interests are in the structure and function of proteins implicated in Parkinson’s disease (PD), parkin and PINK1 in particular. The 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. Objectives are: 1) to elucidate their mechanism of action through structural studies 2) to develop novel therapies for PD based on these structures. The approach consists of deciphering the structural code of these proteins using data from a wide-range of sophisticated techniques such as X-ray crystallography, nuclear magnetic resonance and mass spectrometry. These structures could be used as scaffolds for designing new drugs with enhanced activity, which could help slow down or even stop the degeneration of neurons causing PD.

Youla S. Tsantrizos

Dr. Tsantrizos’ program centers on the design and synthesis of molecular tools that can be used to probe biochemical pathways implicated in human diseases. The lab is currently investigating four biological targets: the human 1. farnesyl pyrophosphate synthase (hFPPS), 2. geranylgeranyl pyrophosphate synthase (hGGPPS), 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 enantioselective synthesis of structurally diverse heterocyclic and peptidomimetic ligands; (c) development of reliable structural and functional assays for guiding structure-activity relationship (SAR) studies. These studies are truly multidisciplinary, involving a seamless integration of synthetic organic chemistry, structural research and biochemistry.

Javier Vargas

My research plan proposes the exploration of present frontiers in cryo-electron microscopy (cryo-EM) to solve key current limitations at the computational and image processing levels. Currently, this imaging technique is living a revolution in its capacity to provide close-to-atomic resolution structures of macromolecules. Cryo-EM uses the electron microscope to study nanoscopic biological samples vitrified at cryogenic temperatures in an amorphous ice layer. However, image processing for the analysis of single particles in cryo-EM is still technically challenging. My research focused on developing innovative computational methods to convert cryo-EM into a trustful and high-performance technique.

Paul W. Wiseman

The Wiseman group works on 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. They characterize cellular signaling, receptor transport and protein interactions in living cells and neurons, with application to cell migration, signal transduction, axon pathfinding and synaptic formation. The group applies new nonlinear microscopy techniques for imaging extracellular matrices and metallic nanoparticles, and detecting malaria-infected blood cells.

Yu (Brandon) Xia

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 the design principles of biological networks and to study the 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

Protein misfolding underlies many diseases. These include genetic diseases of ion channels such as CFTR in cystic fibrosis and hERG in long QT syndrome, as well as neurodegeneration and cancer. Dr. Young’s research studies molecular chaperones, which are key factors in cellular protein folding and quality control. They 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, the laboratory addresses how the Hsp70 system controls the balance between folding, trafficking and proteasomal degradation of misfolded ion channels and other proteins. Also, the lab is investigating the molecular mechanisms of protein refolding and disaggregation by Hsp70, and its potential as a therapeutic drug target in certain cancers.

Marc D. McKee

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

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” behaviour of microorganisms in microfluidic networks.

Jérôme Waldispühl

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