Research

The overarching research theme in the Department of Anatomy and Cell Biology is the study of the assembly, structure and functional dynamics of macromolecular protein complexes. The research interests span a broad variety of topics ranging from the understanding of the mechanisms of bacterial antimicrobial resistance to unveiling the mechanisms of cell division, transport and sorting of proteins, structure and function of extracellular matrices, and the mechanisms of cancer and aging. The Department of Anatomy and Cell Biology also constitutes the biggest cluster of cryo-electron microscopy expertise in Canada with researchers working in the areas of single particle cryo-electron microscopy, cryo-electron tomography, correlative light-electron microscopy and computation for the development of image processing tools.

DEVELOPMENTAL BIOLOGY, STEM CELLS AND AGING

Multicellular organisms require cells to develop into defined cell types. Aging is the cumulative failure of cellular maintenance and repair. Understanding how the development of specific cell types is regulated is key to developing safe and efficient cell replacement therapies for various diseases using stem cells. Researchers seek to understand how cell diversity is generated during organ and nervous system development, how synaptic connections form during neurodevelopment, how myoblast fusion is regulated during muscle development, and how loss of function in fundamental cell processes contributes to aging. Such studies will lead to a better understanding of basic biological mechanisms that define major life transitions, complex mental disorders, and diseases such as muscular dystrophies and nephrotic syndromes.

Faculty
Chantal Autexier
Susanne Bechstedt
Joint Professors
Timothy Kennedy
Wayne Sossin
Stefano Stifani
Claire-Dominique Walker
Associate Professors
Colin Chalk
Jean-Francois Cloutier
Claudio Cuello
Alyson Fournier
Loydie Majewska
Peter Metrakos
Makoto Nagano
Christian Rocheleau
Edward Ruthazer
Peter Siegel
Adjunct Professors
Gregor Andelfinger
Michael Cayouette
Frédéric Charron
Jean-Francois Côté
Daniel Cyr
Patrick Freud
Artur Kania
CELL SIGNALING, CELL/ENVIRONMENT INTERACTIONS AND EXTRACELLULAR MATRIX

Cell signaling and cell interactions with their local environment and the extracellular matrix (ECM) is essential for the development, differentiation and maintenance of cells, tissues and organs. Faculty whose research falls under this theme use a wide variety of innovative approaches and models, studying receptor tyrosine kinase signaling, cell senescence, cell-ECM dynamics, biomineralization, mitochondrial dynamics, pituitary hormone synthesis, and blood flow in the vasculature, to understand how cells integrate signals in response to physical and chemical interactions. Specific cell and physiological processes downstream of these responses include vesicle trafficking, endosome maturation, cell adhesion, migration, morphology, and growth, as well as cellular transitions in metabolic profiles, cell cycle, immune pathway and cell death. This research in this theme is directly relevant to human disease. Genetic mutations in the genes encoding ECM components lead to debilitating defects in blood vessels, bone and skin, while abnormal deposition of minerals in soft tissues such as the kidney and blood vessels lead to various pathologic conditions including urolithiasis and atherosclerosis. Defects in numerous signaling pathways occur in cancer and neurodegenerative diseases. A basic understanding of cell signaling, cell-environment interactions and cell-ECM dynamics will help to design preventative, diagnostic and therapeutic strategies for the associated disorders.

Faculty
Elaine Davis
Nathalie Lamarche-Vane
Dieter Reinhardt
Hojatollah Vali
Joint Professors
Orest Blaschuk
Samuel David
Timothy Kennedy
Marc McKee
Peter McPherson
Alfredo Ribeiro-da-Silva
Wayne Sossin
Associate Professors
Daniel Bernard
Claire Brown
John Di Battista
Allen Ehrlicher
Lisbet Haglund
Mari Kaartinen
Svetlana Komarova
Stéphane Laporte
Stéphanie Lehoux
Heidi McBride
Christian Rocheleau
Edward Ruthazer
Charles Smith
Thomas Stroh
Adjunct Professors
Philippe Campeau
Jean-Francois Côté
Jennifer Estall
Davis Hipfner
CYTOSKELETON AND INTRACELLULAR TRAFFICKING

Cell biologists in this theme use various models (neurons, Chlamydomonas, genetically modified mice and C. elegans) to study the dynamic regulation of cytoskeleton networks such as microtubules that control cell shape and migration and affect cell signaling. Researchers also study the involvement of the cytoskeleton in endocytosis, in chromosome segregation during cytokinesis and the importance of the cytoskeleton for the intracellular transport of vesicles and organelles, such as endosomes, lysosomes and mitochondria. The cytoskeleton forms specialised structures such as cilia and lamellipodia, which play essential roles in the development and function of cells. Understanding the basic cell biology of microtubule dynamics, cilia assembly and function, cytokinesis, and the regulation of vesicle and organelle dynamics and intracellular trafficking is critical to advance treatment options for diseases resulting from defects in these processes, including lysosomal storage disorders, cilia-related diseases, neurodegenerative diseases, and cancer.

Faculty
Susanne Bechstedt
Khanh Huy Bui
Nathalie Lamarche-Vane
Craig Mandato
Carlos Morales
John Presley

 

Associate Professors
Heidi McBride
Christian Rocheleau

Adjunct Professors
Jean-Francois Côté
Stéphane Lefrancois
Alexei Pchejetski
Michael Sacher

GENE EXPRESSION, CELL CYCLE AND CHROMOSOME BIOLOGY

The genome provides the instructions for growth and development of all living organisms. In healthy cells, genome function entails the proper duplication, organization, maintenance, repair and interpretation of the genome. Flaws in any of these processes can lead to hallmarks of aging and cancer such as genome instability, epigenetic alterations, cell senescence, cell death, replicative immortality, resistance to cell death, sustained proliferative signaling and invasion and metastasis. Researchers take various approaches using yeast and mammalian systems to investigate the basic mechanisms underlying normal genome function and how these mechanisms are impaired in diseases, with the ultimate goal of advancing novel therapeutic strategies. The research is focused on a broad range of topics including genome and telomere integrity, proper cell cycle progression, chromosome organization, epigenetic and transcriptional regulation, DNA replication, DNA repair and chromosome segregation.

Faculty
Chantal Autexier
Susanne Bechstedt

Associate Professors
Daniel Bernard
David Labbé
Jason Tanny

Adjunct Professors
Gregor Andelfinger
Jacques Drouin

METHODOLOGY DEVELOPMENT IN CRYO-EM

Cryo-electron microscopy is an exciting imaging technique whereby samples are rapidly frozen and kept in a frozen hydrated state during imaging - typically below -165 ºC. The electron microscope can then deliver snapshots of biological samples as they exist, immobilized in ice. By averaging many images of one type sample, a 3-dimensional reconstruction can be generated that describes molecules of interest, such as proteins, or protein complexes, even down to the amino-acid level. New methods of handling this data are needed to answer specific questions. In particular, the sorting of the individual images of proteins can be a complicated affair - we don’t know what the protein looks like, we don’t know how many different states it will adopt, and there is no guarantee all states behave the same way. We are devising new protocols to deal with these problems computationally, and working out ways to acquire data that circumvents some of the difficulties we encounter. The methods we are working on include: single particle analysis, electron tomography and sub-tomogram averaging, and micro-electron diffraction.

Faculty
Huy Bui
Susanne Bechstedt
Joaquin Ortega
Mike Strauss

STRUCTURE AND FUNCTION OF CELLULAR MACROMOLECULAR ASSEMBLIES

The promise of biomedical research to find treatments for diseases rests in our ability to understand the biology of the cellular processes sustaining life. Major advances are only possible if researchers can directly visualize the enzymes that perform chemical reactions mediating essential cellular processes. The most detailed insights come from atomic structures of macromolecules and complexes involved in these processes in relevant functional states. Faculty whose research falls under this theme seek to understand the fundamental principles governing the structure and mechanism of some of these protein complexes (for example, microtubules, motor proteins, ribosomes, transport proteins and various other enzymes) performing essential roles in bacteria, viruses, and mammalian cells. Solving these structures requires combined approaches and instruments capable of imaging biological specimens at atomic resolution and dissecting their different levels of complexity. Faculty in this theme constitute the largest cluster of cryo-electron microscopy expertise in Canada with researchers working in the areas of single particle cryo-electron microscopy, cryo-electron tomography, correlative light-electron microscopy and computation for the development of image processing tools. These innovative approaches strive to translate the information obtained from cryo-electron microscopy 3D reconstructions of enzymes to understand how they work in their natural environment, the cell. Integration of the structural information at all levels of complexity in living organisms will lead to design principles that can be exploited for synthetic biology and next generation therapeutics. High-resolution structures will also help to elucidate how alterations in these complexes lead to malfunction, causing developmental defects, neurodegenerative disorders, cancer and other diseases.

Faculty
Huy Bui
Susanne Bechstedt
Joaquin Ortega
Dieter Reinhardt
Mike Strauss
Natalie Zeytuni

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