How to reach us:
Universite de Sherbrooke
Faculte des Sciences
Departement de biologie
2500, boul. de l'Universite
Sherbrooke Quebec J1K 2R1
Canada
Office:
Room D8-3064
Telephone:
(819) 821-8000, ext: 65011
Fax:
(819) 821-8049
Lab telephone:
(819) 821-8000, ext: 65413
Daniel Lafontaine Professor Adjunct professor, Universite du Quebec a Montreal (2002-2003) EMBO Post-doctoral Fellow, University of Dundee (UK, 1999-2002) daniel.lafontaine@usherbrooke.ca |
Positions
Positions are available for postdocs, MSc and PhD students.
Research interests
Numerous regulatory mechanisms are known to control gene expression in response to cellular changes. Most well-characterized among these ones are the mechanisms controlling transcription, translation and mRNA stability. Within the past several years, discoveries have revealed that regulatory RNA structures are often used for transcriptional control of essential genes in bacteria and eukaryotes. Riboswitches are untranslated cis-acting mRNA elements that directly bind cellular metabolites and alter the expression of downstream genes that are almost always associated with biosynthesis or transport of a target metabolite. These RNA switches function in absence of protein cofactors and are essentially metabolite sensors using feedback control mechanisms to appropriately modulate the associated metabolite biosynthetic pathway(s). More than 2% of the genes in certain bacteria are riboswitch regulated where many are expected to be essential under most growth conditions; interference with riboswitch function is thus predicted to result in dramatic destabilization of vital metabolic pathways. It is therefore likely that small compounds can serve as antimicrobial drugs by targeting crucial bacterial riboswitches.
In our laboratory, we are studying how metabolites are used by riboswitches to perform their vital biological function. A wide array of techniques is used to monitor the cellular activity of riboswitches and their associated mechanism(s). In addition, we are interested to understand how the folding of RNA is involved in the riboswitch regulation process. Here, given the inherent dynamic nature of riboswitches, we are using Fluorescence Resonance Energy Transfer (FRET) which is one of the most powerful techniques to study the ligand binding-induced RNA folding of riboswitches. We would also like to use lessons learned to develop novel genetic control elements.
In the news
 | Our paper published in PNAS (2021) was highlighted by the Universite de Sherbrooke.You can see it here (in french). |
 | Our paper published in Nature Communications (2017) was highlighted by the Universite de Sherbrooke.You can see it here (in french). |
 | We have presented our research during the TEDxUdeS 2012 event. More information here. |
 | Our research concerning antibiotic development has been mentioned in the Innovation 2011 magazine. More information here. |
 | Our research has recently been honored during the "Gala d'excellence 2011 de la recherche medicale du CHUS". More information here. |
 | We have received from Quebec Science the prize "Decouverte de l'annee 2010" which was awarded by the public. You can read the news here. |
 | Our research on the antibiotic design was selected by Quebec Science as part of the 10 best discoveries of the year 2010. You can read the article here. |
 | Our research has been highlighted in a documentary by Le Code Chastenay in November 2010. You can see it here (in french). |
 | One of our papers has been published in Chemistry and Biology and we have made the cover page. The abstract of the paper is available on the NCBI. |
 | The Courrier des Sciences has published an article that talks about our research (in french) Moreover, our research perceived by the humoristic cartoon Le clin d'oeil du mois made by the biologist Benoit Leblanc. |
|
Selected publications from our lab:
• Regulation of Magnesium Ion Transport in Escherichia coli: Insights into the Role of the 5' Upstream Region in corA Expression.
• Insights into the Cotranscriptional and Translational Control Mechanisms of the Escherichia coli tbpA thiamin pyrophosphate riboswitch.
• Cotranscriptional Folding of a 5' Stem-loop in the Escherichia coli tbpA Riboswitch at Single-nucleotide Resolution.
• Structural Characterization of the Cotranscriptional Folding of the Thiamin Pyrophosphate Sensing thiC Riboswitch in Escherichia coli.
• Fluorescent riboswitch-controlled biosensors for the genome scale analysis of metabolic pathways.
• Riboswitch and small RNAs modulate btuB translation initiation in Escherichia coli and trigger distinct mRNA regulatory mechanisms.
• Direct and Indirect Control of Rho-Dependent Transcription Termination by the Escherichia coli lysC Riboswitch.
• SHAPE-enabled fragment-based ligand discovery for RNA.
• Site-specific photolabile roadblocks for the study of transcription elongation in biologically complex systems.
• Investigating the role of RNA structures in transcriptional pausing using in vitro assays and in silico analyses.
• Monitoring RNA dynamics in native transcriptional complexes.
• Inactivation of the riboswitch-controlled GMP synthase GuaA in Clostridioides difficile is associated with severe growth defects and poor infectivity in a mouse model of infection.
• A structural intermediate pre-organizes the add adenine riboswitch for ligand recognition.
• Riboswitch regulation mechanisms: RNA, metabolites and regulatory proteins.
• Role of a hairpin-stabilized pause in the Escherichia coli thiC riboswitch function.
• Unprecedented tunability of riboswitch structure and regulatory function by sub-millimolar variations in physiological Mg2.
• The yeast telomerase module for telomere recruitment requires a specific RNA architecture.
• Transcriptional pausing at the translation start site operates as a critical checkpoint for riboswitch regulation.
• Cyclic di-GMP riboswitch-regulated type IV pili contribute to aggregation of Clostridium difficile.
• A new telomerase RNA element that is critical for telomere elongation.
• Dual-acting riboswitch control of translation initiation and mRNA decay.
• Molecular insights into the ligand-controlled organization of the SAM-I riboswitch.
• Comparative study between transcriptionally- and translationally-acting adenine riboswitches reveals key differences in riboswitch regulatory mechanisms.
|