Professor Vincent Dion
Professor, Dementia Research Institute
- Available for postgraduate supervision
Overview
We are interested in gene editing and epigenome editing for expanded CAG/CTG repeats. These unusual sequences cause 13 different neurological disorders, including Huntington's disease and myotonic dystrophy. They all remain without effective treatments. We are looking for novel and innovative therapeutic avenues.
Publication
2024
- Larin, M. et al. 2024. Cas9 nickase-mediated contractions of CAG/CTG repeats are transcription-dependent and replication-independent. NAR Molecular Medicine 1(4), article number: ugae013. (10.1093/narmme/ugae013)
- Mangin, A., Dion, V. and Menzies, G. 2024. Developing small Cas9 hybrids using molecular modeling. Scientific Reports 14(1), article number: 17233. (10.1038/s41598-024-68107-1)
2023
- Casella, C. et al. 2023. Differences in white matter detected by ex vivo 9.4T MRI are associated with axonal changes in the R6/1 model of Huntington’s Disease. [Online]. BioRXiv: BioRXiv. (10.1101/2023.10.02.560424) Available at: https://doi.org/10.1101/2023.10.02.560424
2022
- Taylor, A. et al. 2022. Repeat Detector: versatile sizing of expanded tandem repeats and identification of interrupted alleles from targeted DNA sequencing. NAR Genomics and Bioinformatics 4(4), article number: lqac089. (10.1093/nargab/lqac089)
- Yang, B. et al. 2022. Expanded CAGCTG repeats resist gene silencing mediated by targeted epigenome editing. Human Molecular Genetics 31(3), pp. 386-398. (10.1093/hmg/ddab255)
2021
- Wheeler, V. and Dion, V. 2021. Modifiers of CAG repeat instability: insights from mammalian models. Journal of Huntington's Disease 10(1), pp. 123-148. (10.3233/JHD-200426)
2020
- Ruiz Buendía, G. A. et al. 2020. Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion. Science Advances 6(27), article number: eaaz4012. (10.1126/sciadv.aaz4012)
2019
- Cinesi, C., Yang, B. and Dion, V. 2019. GFP reporters to monitor instability and expression of expanded CAG/CTG repeats. In: Richard, G. ed. Trinucleotide Repeats: Methods and Protocols., Vol. 2056. Methods in Molecular Biology Humana Press, pp. 255-268., (10.1007/978-1-4939-9784-8_16)
- Malbec, R. et al. 2019. µLAS: Sizing of expanded trinucleotide repeats with femtomolar sensitivity in less than 5 minutes. Scientific Reports 9(1), article number: 23. (10.1038/s41598-018-36632-5)
2018
- Yang, B., Borgeaud, A., Aeschbach, L. and Dion, V. 2018. Uncovering the interplay between epigenome editing efficiency and sequence context using a novel inducible targeting system. [Online]. bioRxiv. (10.1101/368480) Available at: https://doi.org/10.1101/368480
- Malbec, R. et al. 2018. Direct characterization of circulating DNA in blood plasma using μLAS technology. Presented at: IEEE International Electron Devices Meeting (IEDM 2017), San Francisco, CA, USA, 2-6 December 20172017 IEEE International Electron Devices Meeting (IEDM). IEEE pp. 26.5.1-26.5.4., (10.1109/IEDM.2017.8268465)
2017
- Dion, V. and Aeschbach, L. 2017. Minimizing carry-over PCR contamination in expanded CAG/CTG repeat instability applications. Scientific Reports 7, article number: 18026. (10.1038/s41598-017-18168-2)
2016
- Cinesi, C., Aeschbach, L., Yang, B. and Dion, V. 2016. Contracting CAG/CTG repeats using the CRISPR-Cas9 nickase. Nature Communications 7, article number: 13272. (10.1038/ncomms13272)
2015
- Su, X. A., Dion, V., Gasser, S. M. and Freudenreich, C. H. 2015. Regulation of recombination at yeast nuclear pores controls repair and triplet repeat stability. Genes {&} Development 29(10), pp. 1006--1017. (10.1101/gad.256404.114)
- Horigome, C., Dion, V., Seeber, A., Gehlen, L. R. and Gasser, S. M. 2015. Visualizing the Spatiotemporal Dynamics of DNA Damage in Budding Yeast. In: Stress reponses. Methods in Molecular Biology New York: Springer New York, pp. 77--96., (10.1007/978-1-4939-2522-3_6)
2014
- Horigome, C. et al. 2014. SWR1 and INO80 chromatin remodelers contribute to DNA double-strand break perinuclear anchorage site choice. Molecular Cell 55(4), pp. 626--639. (10.1016/j.molcel.2014.06.027)
- Krawczyk, C., Dion, V., Schar, P. and Fritsch, O. 2014. Reversible Top1 cleavage complexes are stabilized strand-specifically at the ribosomal replication fork barrier and contribute to ribosomal DNA stability. Nucleic Acids Research 42(8), pp. 4985--4995. (10.1093/nar/gku148)
- Seeber, A., Dion, V. and Gasser, S. M. 2014. Remodelers move chromatin in response to DNA damage. Cell Cycle 13(6), pp. 877--878. (10.4161/cc.28200)
- Dion, V. 2014. Tissue specificity in DNA repair: lessons from trinucleotide repeat instability. Trends in Genetics 30(6), pp. 220--229. (10.1016/j.tig.2014.04.005)
2013
- Seeber, A., Dion, V. and Gasser, S. M. 2013. Checkpoint kinases and the INO80 nucleosome remodeling complex enhance global chromatin mobility in response to DNA damage. Genes {&} Development 27(18), pp. 1999--2008. (10.1101/gad.222992.113)
- Dion, V. and Gasser, S. 2013. Chromatin Movement in the Maintenance of Genome Stability. Cell 152(6), pp. 1355--1364. (10.1016/j.cell.2013.02.010)
- Dion, V., Kalck, V., Seeber, A., Schleker, T. and Gasser, S. M. 2013. Cohesin and the nucleolus constrain the mobility of spontaneous repair foci. {EMBO} reports 14(11), pp. 984--991. (10.1038/embor.2013.142)
2012
- Neumann, F. R., Dion, V., Gehlen, L. R., Tsai-Pflugfelder, M., Schmid, R., Taddei, A. and Gasser, S. M. 2012. Targeted INO80 enhances subnuclear chromatin movement and ectopic homologous recombination. Genes {&} Development 26(4), pp. 369--383. (10.1101/gad.176156.111)
- Dion, V., Kalck, V., Horigome, C., Towbin, B. D. and Gasser, S. M. 2012. Increased mobility of double-strand breaks requires Mec1, Rad9 and the homologous recombination machinery. Nature Cell Biology 14(5), pp. 502--509. (10.1038/ncb2465)
2011
- Gehlen, L. R., Gasser, S. M. and Dion, V. 2011. How Broken DNA Finds Its Template for Repair: A Computational Approach. Progress of Theoretical Physics Supplement 191, pp. 20--29. (10.1143/ptps.191.20)
- Hubert, L., Lin, Y., Dion, V. and Wilson, J. H. 2011. Topoisomerase 1 and Single-Strand Break Repair Modulate Transcription-Induced CAG Repeat Contraction in Human Cells. Molecular and Cellular Biology 31(15), pp. 3105--3112. (10.1128/mcb.05158-11)
- Hubert, L., Lin, Y., Dion, V. and Wilson, J. H. 2011. Xpa deficiency reduces CAG trinucleotide repeat instability in neuronal tissues in a mouse model of SCA1. Human Molecular Genetics 20(24), pp. 4822--4830. (10.1093/hmg/ddr421)
2010
- Dion, V., Shimada, K. and Gasser, S. M. 2010. Actin-related proteins in the nucleus: life beyond chromatin remodelers. Current Opinion in Cell Biology 22(3), pp. 383--391. (10.1016/j.ceb.2010.02.006)
2009
- Dion, V. and Wilson, J. H. 2009. Instability and chromatin structure of expanded trinucleotide repeats. Trends in Genetics 25(7), pp. 288--297. (10.1016/j.tig.2009.04.007)
2008
- Dion, V., Lin, Y., Hubert, L., Waterland, R. A. and Wilson, J. H. 2008. Dnmt1 deficiency promotes CAG repeat expansion in the mouse germline. Human Molecular Genetics 17(9), pp. 1306--1317. (10.1093/hmg/ddn019)
- Dion, V., Lin, Y., Price, B. A., Fyffe, S. L., Seluanov, A., Gorbunova, V. and Wilson, J. H. 2008. Genome-wide demethylation promotes triplet repeat instability independently of homologous recombination. {DNA} Repair 7(2), pp. 313--320. (10.1016/j.dnarep.2007.11.002)
- Bystricky, K., Attikum, H. V., Montiel, M., Dion, V., Gehlen, L. and Gasser, S. M. 2008. Regulation of Nuclear Positioning and Dynamics of the Silent Mating Type Loci by the Yeast Ku70/Ku80 Complex. Molecular and Cellular Biology 29(3), pp. 835--848. (10.1128/mcb.01009-08)
2006
- Lin, Y., Dion, V. and Wilson, J. H. 2006. Transcription promotes contraction of CAG repeat tracts in human cells. Nature Structural {&} Molecular Biology 13(2), pp. 179--180. (10.1038/nsmb1042)
- Lin, Y., Dion, V. and Wilson, J. H. 2006. Transcription and triplet repeat instability. In: Genetic instabilities and neurological diseases. Elsevier, pp. 691., (10.1016/b978-012369462-1/50045-4)
2003
- Gorbunova, V., Seluanov, A., Dion, V., Sandor, Z., Meservy, J. L. and Wilson, J. H. 2003. Selectable System for Monitoring the Instability of CTG/CAG Triplet Repeats in Mammalian Cells. Molecular and Cellular Biology 23(13), pp. 4485--4493. (10.1128/mcb.23.13.4485-4493.2003)
Articles
- Larin, M. et al. 2024. Cas9 nickase-mediated contractions of CAG/CTG repeats are transcription-dependent and replication-independent. NAR Molecular Medicine 1(4), article number: ugae013. (10.1093/narmme/ugae013)
- Mangin, A., Dion, V. and Menzies, G. 2024. Developing small Cas9 hybrids using molecular modeling. Scientific Reports 14(1), article number: 17233. (10.1038/s41598-024-68107-1)
- Taylor, A. et al. 2022. Repeat Detector: versatile sizing of expanded tandem repeats and identification of interrupted alleles from targeted DNA sequencing. NAR Genomics and Bioinformatics 4(4), article number: lqac089. (10.1093/nargab/lqac089)
- Yang, B. et al. 2022. Expanded CAGCTG repeats resist gene silencing mediated by targeted epigenome editing. Human Molecular Genetics 31(3), pp. 386-398. (10.1093/hmg/ddab255)
- Wheeler, V. and Dion, V. 2021. Modifiers of CAG repeat instability: insights from mammalian models. Journal of Huntington's Disease 10(1), pp. 123-148. (10.3233/JHD-200426)
- Ruiz Buendía, G. A. et al. 2020. Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion. Science Advances 6(27), article number: eaaz4012. (10.1126/sciadv.aaz4012)
- Malbec, R. et al. 2019. µLAS: Sizing of expanded trinucleotide repeats with femtomolar sensitivity in less than 5 minutes. Scientific Reports 9(1), article number: 23. (10.1038/s41598-018-36632-5)
- Dion, V. and Aeschbach, L. 2017. Minimizing carry-over PCR contamination in expanded CAG/CTG repeat instability applications. Scientific Reports 7, article number: 18026. (10.1038/s41598-017-18168-2)
- Cinesi, C., Aeschbach, L., Yang, B. and Dion, V. 2016. Contracting CAG/CTG repeats using the CRISPR-Cas9 nickase. Nature Communications 7, article number: 13272. (10.1038/ncomms13272)
- Su, X. A., Dion, V., Gasser, S. M. and Freudenreich, C. H. 2015. Regulation of recombination at yeast nuclear pores controls repair and triplet repeat stability. Genes {&} Development 29(10), pp. 1006--1017. (10.1101/gad.256404.114)
- Horigome, C. et al. 2014. SWR1 and INO80 chromatin remodelers contribute to DNA double-strand break perinuclear anchorage site choice. Molecular Cell 55(4), pp. 626--639. (10.1016/j.molcel.2014.06.027)
- Krawczyk, C., Dion, V., Schar, P. and Fritsch, O. 2014. Reversible Top1 cleavage complexes are stabilized strand-specifically at the ribosomal replication fork barrier and contribute to ribosomal DNA stability. Nucleic Acids Research 42(8), pp. 4985--4995. (10.1093/nar/gku148)
- Seeber, A., Dion, V. and Gasser, S. M. 2014. Remodelers move chromatin in response to DNA damage. Cell Cycle 13(6), pp. 877--878. (10.4161/cc.28200)
- Dion, V. 2014. Tissue specificity in DNA repair: lessons from trinucleotide repeat instability. Trends in Genetics 30(6), pp. 220--229. (10.1016/j.tig.2014.04.005)
- Seeber, A., Dion, V. and Gasser, S. M. 2013. Checkpoint kinases and the INO80 nucleosome remodeling complex enhance global chromatin mobility in response to DNA damage. Genes {&} Development 27(18), pp. 1999--2008. (10.1101/gad.222992.113)
- Dion, V. and Gasser, S. 2013. Chromatin Movement in the Maintenance of Genome Stability. Cell 152(6), pp. 1355--1364. (10.1016/j.cell.2013.02.010)
- Dion, V., Kalck, V., Seeber, A., Schleker, T. and Gasser, S. M. 2013. Cohesin and the nucleolus constrain the mobility of spontaneous repair foci. {EMBO} reports 14(11), pp. 984--991. (10.1038/embor.2013.142)
- Neumann, F. R., Dion, V., Gehlen, L. R., Tsai-Pflugfelder, M., Schmid, R., Taddei, A. and Gasser, S. M. 2012. Targeted INO80 enhances subnuclear chromatin movement and ectopic homologous recombination. Genes {&} Development 26(4), pp. 369--383. (10.1101/gad.176156.111)
- Dion, V., Kalck, V., Horigome, C., Towbin, B. D. and Gasser, S. M. 2012. Increased mobility of double-strand breaks requires Mec1, Rad9 and the homologous recombination machinery. Nature Cell Biology 14(5), pp. 502--509. (10.1038/ncb2465)
- Gehlen, L. R., Gasser, S. M. and Dion, V. 2011. How Broken DNA Finds Its Template for Repair: A Computational Approach. Progress of Theoretical Physics Supplement 191, pp. 20--29. (10.1143/ptps.191.20)
- Hubert, L., Lin, Y., Dion, V. and Wilson, J. H. 2011. Topoisomerase 1 and Single-Strand Break Repair Modulate Transcription-Induced CAG Repeat Contraction in Human Cells. Molecular and Cellular Biology 31(15), pp. 3105--3112. (10.1128/mcb.05158-11)
- Hubert, L., Lin, Y., Dion, V. and Wilson, J. H. 2011. Xpa deficiency reduces CAG trinucleotide repeat instability in neuronal tissues in a mouse model of SCA1. Human Molecular Genetics 20(24), pp. 4822--4830. (10.1093/hmg/ddr421)
- Dion, V., Shimada, K. and Gasser, S. M. 2010. Actin-related proteins in the nucleus: life beyond chromatin remodelers. Current Opinion in Cell Biology 22(3), pp. 383--391. (10.1016/j.ceb.2010.02.006)
- Dion, V. and Wilson, J. H. 2009. Instability and chromatin structure of expanded trinucleotide repeats. Trends in Genetics 25(7), pp. 288--297. (10.1016/j.tig.2009.04.007)
- Dion, V., Lin, Y., Hubert, L., Waterland, R. A. and Wilson, J. H. 2008. Dnmt1 deficiency promotes CAG repeat expansion in the mouse germline. Human Molecular Genetics 17(9), pp. 1306--1317. (10.1093/hmg/ddn019)
- Dion, V., Lin, Y., Price, B. A., Fyffe, S. L., Seluanov, A., Gorbunova, V. and Wilson, J. H. 2008. Genome-wide demethylation promotes triplet repeat instability independently of homologous recombination. {DNA} Repair 7(2), pp. 313--320. (10.1016/j.dnarep.2007.11.002)
- Bystricky, K., Attikum, H. V., Montiel, M., Dion, V., Gehlen, L. and Gasser, S. M. 2008. Regulation of Nuclear Positioning and Dynamics of the Silent Mating Type Loci by the Yeast Ku70/Ku80 Complex. Molecular and Cellular Biology 29(3), pp. 835--848. (10.1128/mcb.01009-08)
- Lin, Y., Dion, V. and Wilson, J. H. 2006. Transcription promotes contraction of CAG repeat tracts in human cells. Nature Structural {&} Molecular Biology 13(2), pp. 179--180. (10.1038/nsmb1042)
- Gorbunova, V., Seluanov, A., Dion, V., Sandor, Z., Meservy, J. L. and Wilson, J. H. 2003. Selectable System for Monitoring the Instability of CTG/CAG Triplet Repeats in Mammalian Cells. Molecular and Cellular Biology 23(13), pp. 4485--4493. (10.1128/mcb.23.13.4485-4493.2003)
Book sections
- Cinesi, C., Yang, B. and Dion, V. 2019. GFP reporters to monitor instability and expression of expanded CAG/CTG repeats. In: Richard, G. ed. Trinucleotide Repeats: Methods and Protocols., Vol. 2056. Methods in Molecular Biology Humana Press, pp. 255-268., (10.1007/978-1-4939-9784-8_16)
- Horigome, C., Dion, V., Seeber, A., Gehlen, L. R. and Gasser, S. M. 2015. Visualizing the Spatiotemporal Dynamics of DNA Damage in Budding Yeast. In: Stress reponses. Methods in Molecular Biology New York: Springer New York, pp. 77--96., (10.1007/978-1-4939-2522-3_6)
- Lin, Y., Dion, V. and Wilson, J. H. 2006. Transcription and triplet repeat instability. In: Genetic instabilities and neurological diseases. Elsevier, pp. 691., (10.1016/b978-012369462-1/50045-4)
Conferences
- Malbec, R. et al. 2018. Direct characterization of circulating DNA in blood plasma using μLAS technology. Presented at: IEEE International Electron Devices Meeting (IEDM 2017), San Francisco, CA, USA, 2-6 December 20172017 IEEE International Electron Devices Meeting (IEDM). IEEE pp. 26.5.1-26.5.4., (10.1109/IEDM.2017.8268465)
Websites
- Casella, C. et al. 2023. Differences in white matter detected by ex vivo 9.4T MRI are associated with axonal changes in the R6/1 model of Huntington’s Disease. [Online]. BioRXiv: BioRXiv. (10.1101/2023.10.02.560424) Available at: https://doi.org/10.1101/2023.10.02.560424
- Yang, B., Borgeaud, A., Aeschbach, L. and Dion, V. 2018. Uncovering the interplay between epigenome editing efficiency and sequence context using a novel inducible targeting system. [Online]. bioRxiv. (10.1101/368480) Available at: https://doi.org/10.1101/368480
- Malbec, R. et al. 2019. µLAS: Sizing of expanded trinucleotide repeats with femtomolar sensitivity in less than 5 minutes. Scientific Reports 9(1), article number: 23. (10.1038/s41598-018-36632-5)
- Cinesi, C., Aeschbach, L., Yang, B. and Dion, V. 2016. Contracting CAG/CTG repeats using the CRISPR-Cas9 nickase. Nature Communications 7, article number: 13272. (10.1038/ncomms13272)
- Su, X. A., Dion, V., Gasser, S. M. and Freudenreich, C. H. 2015. Regulation of recombination at yeast nuclear pores controls repair and triplet repeat stability. Genes {&} Development 29(10), pp. 1006--1017. (10.1101/gad.256404.114)
- Horigome, C., Dion, V., Seeber, A., Gehlen, L. R. and Gasser, S. M. 2015. Visualizing the Spatiotemporal Dynamics of DNA Damage in Budding Yeast. In: Stress reponses. Methods in Molecular Biology New York: Springer New York, pp. 77--96., (10.1007/978-1-4939-2522-3_6)
- Horigome, C. et al. 2014. SWR1 and INO80 chromatin remodelers contribute to DNA double-strand break perinuclear anchorage site choice. Molecular Cell 55(4), pp. 626--639. (10.1016/j.molcel.2014.06.027)
- Krawczyk, C., Dion, V., Schar, P. and Fritsch, O. 2014. Reversible Top1 cleavage complexes are stabilized strand-specifically at the ribosomal replication fork barrier and contribute to ribosomal DNA stability. Nucleic Acids Research 42(8), pp. 4985--4995. (10.1093/nar/gku148)
- Seeber, A., Dion, V. and Gasser, S. M. 2014. Remodelers move chromatin in response to DNA damage. Cell Cycle 13(6), pp. 877--878. (10.4161/cc.28200)
- Dion, V. 2014. Tissue specificity in DNA repair: lessons from trinucleotide repeat instability. Trends in Genetics 30(6), pp. 220--229. (10.1016/j.tig.2014.04.005)
- Seeber, A., Dion, V. and Gasser, S. M. 2013. Checkpoint kinases and the INO80 nucleosome remodeling complex enhance global chromatin mobility in response to DNA damage. Genes {&} Development 27(18), pp. 1999--2008. (10.1101/gad.222992.113)
- Dion, V. and Gasser, S. 2013. Chromatin Movement in the Maintenance of Genome Stability. Cell 152(6), pp. 1355--1364. (10.1016/j.cell.2013.02.010)
- Dion, V., Kalck, V., Seeber, A., Schleker, T. and Gasser, S. M. 2013. Cohesin and the nucleolus constrain the mobility of spontaneous repair foci. {EMBO} reports 14(11), pp. 984--991. (10.1038/embor.2013.142)
- Neumann, F. R., Dion, V., Gehlen, L. R., Tsai-Pflugfelder, M., Schmid, R., Taddei, A. and Gasser, S. M. 2012. Targeted INO80 enhances subnuclear chromatin movement and ectopic homologous recombination. Genes {&} Development 26(4), pp. 369--383. (10.1101/gad.176156.111)
- Dion, V., Kalck, V., Horigome, C., Towbin, B. D. and Gasser, S. M. 2012. Increased mobility of double-strand breaks requires Mec1, Rad9 and the homologous recombination machinery. Nature Cell Biology 14(5), pp. 502--509. (10.1038/ncb2465)
- Gehlen, L. R., Gasser, S. M. and Dion, V. 2011. How Broken DNA Finds Its Template for Repair: A Computational Approach. Progress of Theoretical Physics Supplement 191, pp. 20--29. (10.1143/ptps.191.20)
- Hubert, L., Lin, Y., Dion, V. and Wilson, J. H. 2011. Topoisomerase 1 and Single-Strand Break Repair Modulate Transcription-Induced CAG Repeat Contraction in Human Cells. Molecular and Cellular Biology 31(15), pp. 3105--3112. (10.1128/mcb.05158-11)
- Hubert, L., Lin, Y., Dion, V. and Wilson, J. H. 2011. Xpa deficiency reduces CAG trinucleotide repeat instability in neuronal tissues in a mouse model of SCA1. Human Molecular Genetics 20(24), pp. 4822--4830. (10.1093/hmg/ddr421)
- Dion, V., Shimada, K. and Gasser, S. M. 2010. Actin-related proteins in the nucleus: life beyond chromatin remodelers. Current Opinion in Cell Biology 22(3), pp. 383--391. (10.1016/j.ceb.2010.02.006)
- Dion, V. and Wilson, J. H. 2009. Instability and chromatin structure of expanded trinucleotide repeats. Trends in Genetics 25(7), pp. 288--297. (10.1016/j.tig.2009.04.007)
- Dion, V., Lin, Y., Hubert, L., Waterland, R. A. and Wilson, J. H. 2008. Dnmt1 deficiency promotes CAG repeat expansion in the mouse germline. Human Molecular Genetics 17(9), pp. 1306--1317. (10.1093/hmg/ddn019)
- Dion, V., Lin, Y., Price, B. A., Fyffe, S. L., Seluanov, A., Gorbunova, V. and Wilson, J. H. 2008. Genome-wide demethylation promotes triplet repeat instability independently of homologous recombination. {DNA} Repair 7(2), pp. 313--320. (10.1016/j.dnarep.2007.11.002)
- Bystricky, K., Attikum, H. V., Montiel, M., Dion, V., Gehlen, L. and Gasser, S. M. 2008. Regulation of Nuclear Positioning and Dynamics of the Silent Mating Type Loci by the Yeast Ku70/Ku80 Complex. Molecular and Cellular Biology 29(3), pp. 835--848. (10.1128/mcb.01009-08)
- Lin, Y., Dion, V. and Wilson, J. H. 2006. Transcription promotes contraction of CAG repeat tracts in human cells. Nature Structural {&} Molecular Biology 13(2), pp. 179--180. (10.1038/nsmb1042)
- Lin, Y., Dion, V. and Wilson, J. H. 2006. Transcription and triplet repeat instability. In: Genetic instabilities and neurological diseases. Elsevier, pp. 691., (10.1016/b978-012369462-1/50045-4)
- Gorbunova, V., Seluanov, A., Dion, V., Sandor, Z., Meservy, J. L. and Wilson, J. H. 2003. Selectable System for Monitoring the Instability of CTG/CAG Triplet Repeats in Mammalian Cells. Molecular and Cellular Biology 23(13), pp. 4485--4493. (10.1128/mcb.23.13.4485-4493.2003)
Research
Expanded CAG/CTG repeats cause over 13 neurological and neuromuscular disorders, including Huntington disease, myotonic dystrophy, and several spinocerebellar ataxias. The diseases are debilitating, often leading to dementia. There is no available cure. Individually expanded repeat disorders are rare but together account for about 1 in 2000 people worldwide.
Our goal is to develop novel therapeutic avenues by targeting the unique features of expanded CAG/CTG repeats and to develop new technologies to detect (i.e., diagnose) and manipulate them. To achieve this, we use a variety of tools, including cutting edge molecular biology and genome engineering technologies, next-generation sequencing, as well as in vitro and in vivo pre-clinical disease models.
My laboratory has three main focal areas:
1) Gene editing and the mechanism of expanded CAG/CTG repeat instability
Expanded CAG/CTG repeats are highly unstable somatically, leading to mutation frequencies of 100% in some tissues. The size of the repeat tract determines in large part the severity of the disease. Understanding this mechanism is essential to designing and optimising treatments aimed at contracting the repeat tract.
We have recently developed a gene editing-based approach to contract the expanded repeat tract using the CRISPR-Cas9 system. We are currently determining whether this technology is applicable to contract and slow, prevent, or reverse the disease phenotypes in cells and in vivo. Moreover, we are studying the mechanisms of repeat contraction with the aim of improving the efficacy of inducing contractions.
Representative reference: Cinesi, C., Aeschbach, L., Yang, B. and Dion, V. (2016) Contracting CAG/CTG repeats using the CRISPR-Cas9 nickase. Nat Commun, 7, 13272.
2) The role of chromatin structure in the expression of expanded CAG/CTG repeats
Expanded CAG/CTG repeats accumulate chromatin marks reminiscent of heterochromatin and are downregulated (but not completely silenced) compared to normal size repeats. In addition, there is genetic and biochemical evidence that expanded repeats require extra factors for efficient expression. Identifying these factors and identifying their mode of action may lead to the development of epigenome editing approaches to combat expanded CAG/CTG repeat disorders.
We have developed a novel inducible chromatin targeting assay that allows us to determine which factors can change gene expression of expanded CAG/CTG repeats specifically. With this method, we can start to uncover a way forward to silence expanded repeats specifically.
Moreover, changes in chromatin marks is often associated with changes in higher order folding. We tested the prevalent hypothesis the expanded CAG/CTG repeats change chromatin folding, which impinges on repeat instability, changes in gene expression, and pathogenesis of Huntington's disease and myotonic dystrophy type 1. Using both molecular biology and bioinformatics, we find that this is not the case.
3) Development of tools to manipulate and detect expanded CAG/CTG repeats
Determining repeat size for diagnostic purposes and for routine molecular biology applications is laborious. This is because of the repetitive nature and the inherent heterogeneity of the repeat size from cell to cell (i.e., repeat instability). Thus, there is a great need to improve on the current technologies. In addition, such system will help us determine whether any therapies involving contracting the repeat tracts are effective.
Towards these goals, we are developing, in collaboration with the laboratory of Aurélien Bancaud (LAAS, France), microfluidics-based technologies for sizing expanded repeats. In addition, we have an ongoing collaboration with Ioannis Xenarios (UNIL, Switzerland) to develop sequencing-based approaches for these purposes.
Biography
Vincent Dion started his scientific career in 1999 as a summer student in Stanley L. Miller's laboratory at UCSD (USA). He also spent time as an undergraduate in the laboratories of Benoit Chabot and Reymund Wellinger at the University of Sherbrooke (Canada). He completed his B.Sc. in molecular biology and genetics in 2002 at the University of Guelph (Canada) with a honours thesis supervised by David H. Evans. In 2007, he obtained his PhD from Baylor College of Medicine (USA), under the supervision of John H. Wilson, for defining the role of DNMT1, the maintenance DNA methyltransferase, in preventing disease-causing CAG/CTG repeat expansions. As a postdoc with Susan M. Gasser at the Friedrich Miescher Institute (Switzerland), he discovered a novel role for chromatin remodeling enzymes in the repair of deleterious DNA double-strand breaks. He joined the Center for Integrative Genomics at the University of Lausanne (Switzerland) in 2013 on a professorship from the Swiss National Science Foundation. He became Professor at the UK Dementia Research Institut at Cardiff University in January of 2019. His lab has made key contributions towards the development of gene editing approaches to correct mutations that cause 14 different neurological, neuromuscular, and neurodegenerative diseases, which all remain without a cure.
Supervisions
How to apply
Guidelines to write a cover letter for prospective PhD and postdocs
The goal of a cover letter is to convince the group leader to open your CV. No more, no less. Consequently, you need to keep it short (~250 words or less) and to the point. People are more likely to read something short. Your letter must contain the answer to two big questions:
- Why are you interested in this particular lab? This has to be as precise as possible. Broad answers to this questions, for example stating that you "want to join an outstanding institution", are not compelling. Be specific. Why are you interested in our lab and not the lab next door? Why is the topic of the lab interesting to you? In other words, I want to know why you are applying to my lab and that you are not simply sending mass e-mails hoping that something will stick.
- What do you bring to the lab? This can be knowledge of a specific technique or field. Listing the techniques you are familiar with is not necessary as they should be in your CV, makes your cover letter longer, and generally does not help your case. Another way of phrasing this question is "What makes you stand out and be particularly well suited to join the lab?" It is not a problem if your area of expertise is outside that of the lab – it can be an advantage. But then you will have to emphasize why you are applying, which brings you back to why you are interested in this particular lab.
Some more tips:
- Make the letter personal and custom-tailored. A good way to make the letter stand out is to explain the research topic of the lab in your own words. You will have to do it well (and briefly), however, as it can backfire if not done properly. Do not copy and paste from the lab's website or papers.
- Start the letter with why you are writing. Often letters start with "I am So and So from University X". This is superfluous information as it is at the bottom of the e-mail and/or in your CV.
- Writing a letter free of typos and grammatical mistakes is a good way to make a good first impression. Avoid overly flowery language (e.g., Dear Esteemed Sir) and using "Greetings" as an opening.
- A specificity of Cardiff University is that if you are responding to a job advert, the job descriptions are divided into essential and desirable criteria. To obtain an interview you have to meet all the essential criteria. In your cover letter, list the essential criteria and explain how you meet them. It does not hurt to do so for the desirable criteria also. This makes the shortlisting easier and increases your chances of getting an interview. This part does not count towards the ~250 word guideline above, but it helps to keep it consice.
Quality and care in a letter will take you time, but it will make an enormous difference: many fewer requests will go unanswered. Remember that top labs want to hire passionate, motivated, and hard-working people. A well written letter should convey that you possess these qualities!
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