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How to reach us:
Universite de Sherbrooke
Faculte des Sciences
Departement de biologie
2500, boul. de l'Universite
Sherbrooke Quebec J1K 2R1

Room D8-3064

(819) 821-8000, ext: 65011

(819) 821-8049

Lab telephone:
(819) 821-8000, ext: 65413

Daniel Lafontaine

Adjunct professor, Universite du Quebec a Montreal (2002-2003)
EMBO Post-doctoral Fellow, University of Dundee (UK, 1999-2002)

Member of the following organizations:
Universite de Sherbrooke Centre of Excellence in RNA Biology
Institut de Pharmacologie de Sherbrooke


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.

Research group

Selected publications from our lab:

• SHAPE-enabled fragment-based ligand discovery for RNA.
Zeller MJ, Favorov O, Li K, Nuthanakanti A, Hussein D, Michaud A, Lafontaine DA, Busan S, Serganov A, Aube J, Weeks KM.
Proc Natl Acad Sci U S A., In press, 2022.

• Site-specific photolabile roadblocks for the study of transcription elongation in biologically complex systems.
Nadon JF, Epshtein V, Cameron E, Samatov MR, Vasenko AS, Nudler E, Lafontaine DA.
Commun. Biol., In press, 2022.

• Monitoring RNA dynamics in native transcriptional complexes.
Chauvier A, St-Pierre P, Nadon JF, Hien E, Perez-Gonzalez C, Eschbach SH, Lamontagne AM, Penedo JC, Lafontaine DA.
Proc Natl Acad Sci U S A., 118(45), 2021.

• 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.
Smith-Peter E, Lalonde Seguin D, St-Pierre E, Sekulovic O, Jeanneau S, Tremblay-Tetreault C, Lamontagne AM, Lafontaine DA, Fortier LC.
RNA Biol, 18, 2021.

• A structural intermediate pre-organizes the add adenine riboswitch for ligand recognition.
St-Pierre P, Shaw E, Jacques S, Dalgarno PA, Perez-Gonzalez C, Picard-Jean F, Penedo JC, Lafontaine DA..
Nucleic Acids Res, 49(10), 2021.

• Riboswitch regulation mechanisms: RNA, metabolites and regulatory proteins.
Bedard AV, Hien EDM, Lafontaine DA.
Biochim Biophys Acta Gene Regul Mech, 1863(63), 2020.

• Role of a hairpin-stabilized pause in the Escherichia coli thiC riboswitch function.
Chauvier A, Nadon JF, Grondin JP, Lamontagne AM, Lafontaine DA.
RNA Biol, 16(8), 2019.

• Unprecedented tunability of riboswitch structure and regulatory function by sub-millimolar variations in physiological Mg2.
McCluskey K, Boudreault J, St-Pierre P, Perez-Gonzalez C, Chauvier A, Rizzi A, Beauregard PB, Lafontaine DA, Penedo JC.
Nucleic Acids Res, 47(12), 2019.

• The yeast telomerase module for telomere recruitment requires a specific RNA architecture.
Laterreur N, Lemieux B, Neumann H, Berger-Dancause JC, Lafontaine D, Wellinger RJ.
RNA, 24(8), 2018.

• Transcriptional pausing at the translation start site operates as a critical checkpoint for riboswitch regulation.
Chauvier A, Picard-Jean F, Berger-Dancause JC, Bastet L, Naghdi MR, Dube A, Turcotte P, Perreault J, Lafontaine DA.
Nature Communications, 8:13892, 2017.

• Cyclic di-GMP riboswitch-regulated type IV pili contribute to aggregation of Clostridium difficile.
Bordeleau E, Purcell EB, Lafontaine DA, Fortier LC, Tamayo R, Burrus V.
J Bacteriol, 197:819-32, 2015.

• A new telomerase RNA element that is critical for telomere elongation.
Laterreur N, Eschbach S, Lafontaine DA, Wellinger R.
Nucleic Acids Res, 41:7713-24, 2013.

• Dual-acting riboswitch control of translation initiation and mRNA decay.
Caron MP, Bastet L, Lussier A, Simoneau-Roy M, Masse E, Lafontaine DA.
Proceedings of the National Academy of Science USA, 109:E3444-53, 2012.

• Molecular insights into the ligand-controlled organization of the SAM-I riboswitch.
Heppell B, Blouin S, Dussault AM, Mulhbacher J, Ennifar E, Penedo JC, Lafontaine DA.
Nature Chem Biol, 7:384-92, 2011.

• Comparative study between transcriptionally- and translationally-acting adenine riboswitches reveals key differences in riboswitch regulatory mechanisms.
Lemay JF, Desnoyers G, Blouin S, Heppell B, Bastet L, St-Pierre P, Masse E, Lafontaine DA.
PLoS Genetics, 7:e1001278, 2011.