Publications by authors named "Marie-Eve Paquet"

9 Publications

  • Page 1 of 1

Zebrafish: a big fish in the study of the gut microbiota.

Curr Opin Biotechnol 2021 Oct 12;73:308-313. Epub 2021 Oct 12.

Département de biochimie, de microbiologie et de bio-informatique, Faculté des sciences et de génie, Université Laval, Québec, QC, G1V 0A6, Canada; Groupe de recherche en écologie buccale, Faculté de médecine dentaire, Université Laval, Québec, QC, G1V 0A6, Canada; Félix d'Hérelle Reference Center for Bacterial Viruses, Université Laval, Québec, QC, G1V 0A6, Canada. Electronic address:

The importance of the gut microbiota in host health is now well established, but the underlying mechanisms remain poorly understood. Among the animal models used to investigate microbiota-host interactions, the zebrafish (Danio renio) is gaining attention. Several factors contribute to the recent interest in this model, including its low cost, the ability to assess large cohorts, the possibility to obtain germ-free larvae from non-axenic parents, and the availability of optical methodologies to probe the transparent larvae and adults from various genetic lines. We review recent findings on the zebrafish gut microbiota and its modulation by exogenous microbes, nutrition, and environmental factors. We also highlight the potential of this model for assessing the impact of the gut microbiota on brain development.
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http://dx.doi.org/10.1016/j.copbio.2021.09.007DOI Listing
October 2021

Challenges for Therapeutic Applications of Opsin-Based Optogenetic Tools in Humans.

Front Neural Circuits 2020 15;14:41. Epub 2020 Jul 15.

Centre de Recherche CERVO, Université Laval, Quebec City, QC, Canada.

As the technological hurdles are overcome and optogenetic techniques advance to have more control over neurons, therapies based on these approaches will begin to emerge in the clinic. Here, we consider the technical challenges surrounding the transition of this breakthrough technology from an investigative tool to a true therapeutic avenue. The emerging strategies and remaining tasks surrounding genetically encoded molecules which respond to light as well as the vehicles required to deliver them are discussed.The use of optogenetics in humans would represent a completely new paradigm in medicine and would be associated with unprecedented technical considerations. To be applied for stimulation of neurons in humans, an ideal optogenetic tool would need to be non-immunogenic, highly sensitive, and activatable with red light or near-infrared light (to maximize light penetration while minimizing photodamage). To enable sophisticated levels of neuronal control, the combined use of optogenetic actuators and indicators could enable closed-loop all-optical neuromodulation. Such systems would introduce additional challenges related to spectral orthogonality between actuator and indicator, the need for decision making computational algorithms and requirements for large gene cassettes. As in any gene therapy, the therapeutic efficiency of optogenetics will rely on vector delivery and expression in the appropriate cell type. Although viral vectors such as those based on AAVs are showing great potential in human trials, barriers to their general use remain, including immune responses, delivery/transport, and liver clearance. Limitations associated with the gene cassette size which can be packaged in currently approved vectors also need to be addressed.
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http://dx.doi.org/10.3389/fncir.2020.00041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373823PMC
October 2021

Probing pain pathways with light.

Neuroscience 2016 Dec 1;338:248-271. Epub 2016 Oct 1.

Institut universitaire en santé mentale de Québec, Université Laval, Québec, QC, Canada; Centre d'optique, photonique et laser, Université Laval, Québec, QC, Canada; Département de psychiatrie et neurosciences, Université Laval, Québec, QC, Canada. Electronic address:

We have witnessed an accelerated growth of photonics technologies in recent years to enable not only monitoring the activity of specific neurons, while animals are performing certain types of behavior, but also testing whether specific cells, circuits, and regions are sufficient or necessary for initiating, maintaining, or altering this or that behavior. Compared to other sensory systems, however, such as the visual or olfactory system, photonics applications in pain research are only beginning to emerge. One reason pain studies have lagged behind is that many of the techniques originally developed cannot be directly implemented to study key relay sites within pain pathways, such as the skin, dorsal root ganglia, spinal cord, and brainstem. This is due, in part, to difficulties in accessing these structures with light. Here we review a number of recent advances in design and delivery of light-sensitive molecular probes (sensors and actuators) into pain relay circuits to help decipher their structural and functional organization. We then discuss several challenges that have hampered hardware access to specific structures including light scattering, tissue movement and geometries. We review a number of strategies to circumvent these challenges, by delivering light into, and collecting it from the different key sites to unravel how nociceptive signals are encoded at each level of the neuraxis. We conclude with an outlook on novel imaging modalities for label-free chemical detection and opportunities for multimodal interrogation in vivo. While many challenges remain, these advances offer unprecedented opportunities to bridge cellular approaches with context-relevant behavioral testing, an essential step toward improving translation of basic research findings into clinical applications.
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http://dx.doi.org/10.1016/j.neuroscience.2016.09.035DOI Listing
December 2016

Derlin-2-deficient mice reveal an essential role for protein dislocation in chondrocytes.

Mol Cell Biol 2011 Mar 10;31(6):1145-59. Epub 2011 Jan 10.

Whitehead Institute for Biomedical Research, 9 Cambridge Center, Rm. 361, Cambridge, MA 02142, USA.

Protein quality control is a balance between chaperone-assisted folding and removal of misfolded proteins from the endoplasmic reticulum (ER). Cell-based assays have been used to identify key players of the dislocation machinery, including members of the Derlin family. We generated conditional knockout mice to examine the in vivo role of Derlin-2, a component that nucleates cellular dislocation machinery. In most Derlin-2-deficient tissues, we found constitutive upregulation of ER chaperones and IRE-1-mediated induction of the unfolded protein response. The IRE-1/XBP-1 pathway is required for development of highly secretory cells, particularly plasma cells and hepatocytes. However, B lymphocyte development and antibody secretion were normal in the absence of Derlin-2. Likewise, hepatocyte function was unaffected by liver-specific deletion of Derlin-2. Whole-body deletion of Derlin-2 results in perinatal death. The few mice that survived to adulthood all developed skeletal dysplasia, likely caused by defects in collagen matrix protein secretion by costal chondrocytes.
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http://dx.doi.org/10.1128/MCB.00967-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067910PMC
March 2011

UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes.

Nature 2008 Mar 27;452(7184):234-8. Epub 2008 Feb 27.

Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.

Signalling by means of toll-like receptors (TLRs) is essential for the development of innate and adaptive immune responses. UNC93B1, essential for signalling of TLR3, TLR7 and TLR9 in both humans and mice, physically interacts with these TLRs in the endoplasmic reticulum (ER). Here we show that the function of the polytopic membrane protein UNC93B1 is to deliver the nucleotide-sensing receptors TLR7 and TLR9 from the ER to endolysosomes. In dendritic cells of 3d mice, which express an UNC93B1 missense mutant (H412R) incapable of TLR binding, neither TLR7 nor TLR9 exits the ER. Furthermore, the trafficking and signalling defects of the nucleotide-sensing TLRs in 3d dendritic cells are corrected by expression of wild-type UNC93B1. However, UNC93B1 is dispensable for ligand recognition and signal initiation by TLRs. To our knowledge, UNC93B1 is the first protein to be identified as a molecule specifically involved in trafficking of nucleotide-sensing TLRs. By inhibiting the interaction between UNC93B1 and TLRs it should be possible to achieve specific regulation of the nucleotide-sensing TLRs without compromising signalling via the cell-surface-disposed TLRs.
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http://dx.doi.org/10.1038/nature06726DOI Listing
March 2008

Viral interference with B7-1 costimulation: a new role for murine cytomegalovirus fc receptor-1.

J Immunol 2006 Dec;177(12):8422-31

Department of Pathology, Harvard Medical School, Boston, MA 02115. USA.

Murine CMV (MCMV), a beta-herpesvirus, infects dendritic cells (DC) and impairs their function. The underlying events are poorly described. In this study, we identify MCMV m138 as the viral gene responsible for promoting the rapid disappearance of the costimulatory molecule B7-1 (CD80) from the cell surface of DC. This was unexpected, as m138 was previously identified as fcr-1, a putative virus-encoded FcR. m138 impaired the ability of DC to activate CD8+ T cells. Biochemical analysis and immunocytochemistry showed that m138 targets B7-1 in the secretory pathway and reroutes it to lysosomal associated membrane glycoprotein-1+ compartments. These results show a novel function for m138 in MCMV infection and identify the first viral protein to target B7-1.
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http://dx.doi.org/10.4049/jimmunol.177.12.8422DOI Listing
December 2006

In vitro and in vivo assays to assess the functions of calnexin and calreticulin in ER protein folding and quality control.

Methods 2005 Apr;35(4):338-47

Department of Biochemistry, University of Toronto, Toronto, Canada M5S 1A8.

Newly synthesized polypeptides entering the endoplasmic reticulum (ER) encounter a large array of molecular chaperones and folding factors that facilitate proper folding as well as assess folding status, retaining non-native proteins within the ER. Calnexin (CNX), an ER membrane protein, and its soluble homologue, calreticulin (CRT), are two important molecular chaperones that contribute to both processes. They are highly unusual chaperones in that they act as lectins, binding the Asn-linked oligosaccharides of newly synthesized glycoproteins, as well as recognizing the polypeptide segments of glycoproteins. Furthermore, they associate with ERp57, a thiol oxidoreductase, that is thought to enhance the oxidative folding of glycoproteins bound to CNX/CRT. These characteristics of CNX and CRT as well as their mode of action have been elucidated though the use of multiple in vitro and in vivo approaches. This chapter will focus on the description of a number of in vitro assays that have been used to characterize the lectin and ERp57-binding functions of CNX/CRT and also their abilities to act as molecular chaperones to suppress protein aggregation. In addition, we will describe insect and mammalian expression systems in which major histocompatibility complex class I molecules are used as model glycoprotein substrates for CNX and CRT. These systems have been valuable in assessing folding and quality control events in vivo that are influenced by CNX or CRT as well as in characterizing the spectrum of substrates that are recognized by these chaperones.
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http://dx.doi.org/10.1016/j.ymeth.2004.10.005DOI Listing
April 2005

Bap29/31 influences the intracellular traffic of MHC class I molecules.

J Immunol 2004 Jun;172(12):7548-55

Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

In this study, we examine the role of the putative cargo receptor B cell-associated protein (Bap)29/31 in the export of MHC class I molecules out of the endoplasmic reticulum (ER). We show that Bap31 binds to two allotypes of mouse class I molecules, with the interaction initiated at the time of H chain association with beta(2)-microglobulin and maintained until the class I molecule has left the ER. We also show that Bap31 is part of the peptide-loading complex, although is not required for its formation. Bap31 binds not only to class I molecules, but can bind to tapasin in the absence of class I. Consistent with an important role in recruiting class I molecules to transport vesicles, we show that in the absence of Bap29/31, there is a loss of class I colocalization with mSec31 (p137), a component of mammalian coat protein complex II coats. This observation is also associated with a delay in class I traffic from ER to Golgi. Our results are consistent with the view that class I molecules are largely recruited to ER exit sites by Bap29/31, and that Bap29/31 is a cargo receptor for MHC class I molecules.
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http://dx.doi.org/10.4049/jimmunol.172.12.7548DOI Listing
June 2004

Mutant MHC class I molecules define interactions between components of the peptide-loading complex.

Int Immunol 2002 Apr;14(4):347-58

Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

Class I histocompatibility molecules, consisting of a heavy chain, beta2-microglobulin and peptide, are assembled in the endoplasmic reticulum (ER) with the assistance of several molecular chaperones and accessory proteins. Peptide binding occurs when assembling class I molecules associate with a loading complex consisting of the transporter associated with antigen processing (TAP) peptide transporter, tapasin, ERp57 and calreticulin (CRT)/calnexin. To assess the physical organization of this complex, we generated a series of mutants in the murine H-2Dd heavy chain and assessed their association with components of the complex. Seven mutations, clustered between amino acids 122 and 136 in the heavy chain alpha2 domain plus one mutation at position 222 in the alpha3 domain, resulted in loss of interaction with tapasin. Association with TAP was always lost simultaneously, supporting the view that tapasin acts as an obligatory bridge between class I molecules and TAP. Compared with previous studies on the HLA-A2 molecule, some differences in points of tapasin interaction were observed. Failure of the H-2Dd mutants to bind tapasin resulted in low cell-surface expression and altered intracellular transport. Most mutants retained a substantial degree of peptide loading, consistent with the view that although tapasin may promote peptide binding to class I, it is not required. A surprising observation was that all mutants lacking tapasin interaction retained normal association with CRT. This contrasts with previous observations on other class I molecules and, combined with differences in tapasin interaction, suggests that the organization of the ER peptide-loading complex can vary depending on the specific class I molecule examined.
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http://dx.doi.org/10.1093/intimm/14.4.347DOI Listing
April 2002
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