Yr Athro Vincent Dion
Professor, Dementia Research Institute
- dionv@cardiff.ac.uk
- +44(0)29 2251 0893
- 1.03 - Office J, Adeilad Hadyn Ellis, Heol Maendy, Caerdydd, CF24 4HQ
- Ar gael fel goruchwyliwr ôl-raddedig
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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.
Bywgraffiad
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.
Cyhoeddiadau
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
- 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)
- 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)
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
- 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)
- 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)
2006
- 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)
- 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)
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)
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.
Supervision
How to apply
Guidelines to writing 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!
Past projects
Current lab members
Marcela Buricova (Research Assistant) completed her BSc in Biology and MSc in Animal Physiology at University of South Bohemia. During her BSc and MSc, she researched aging using the linden bug as a model. For her PhD, Marcela moved to the field of chronobiology as a part of the Marie Curie Initial Training Network Fellowship on Insect Timing (INsecTIME). The project was a collaboration between Prof. L.W. Beukeboom of the University of Groningen and Dr E. Tauber of the University of Leicester, studying light synchronisation of circadian and seasonal rhythms in the parasitic wasp Nasonia vitripennis. After a short Lab Manager role at the MRC London School of Medical Sciences in the Cochemé Redox Metabolism group, she joined the lab in Cardiff as a Research Assistant.
Elliot Gibbons (Undergraduate) is a BIOSCI undergraduate studying at Cardiff University. He is currently undertaking a Placement Training Year (PTY), having started in the lab in September 2019. He hopes to graduate with a Biochemistry BSc in 2021, having gained valuable practical experience working in the lab.
Florence Gidney (Senior Technician) completed her BSc in Biomedical Sciences in 2016 from the University of Southampton, where she completed a laboratory research project on the multidrug resistance protein 1, its mechanism of action, and pharmaceutical methods of inhibiting the protein. She has recently completed a Master’s degree in Neuroimaging from Cardiff University, her thesis focussing on central obesity and its association with impaired white matter microstructure in key areas known to be damaged in late-onset Alzheimer’s Disease. Now you can find her wandering the lab, singing, much to the dismay of her colleagues.
Laura Heraty (PhD Student) completed her BSc in Biochemistry and Genetics from the University of Sheffield in June 2018. She then went on to undertake a MSc in Translational Neuropathology at the same university but within the Sheffield Institute for Translational Neuroscience (SITraN), which she completed in August 2019. Her project focused on Motor Neuron Disease, specifically focusing on the role of microglia in the disease. In the Dion lab, she is working on the mechanism of contractions of expanded CAG/CTG repeats.
Meghan Larin (Postdoc/Research Associate) grew up in Ontario, Canada. In the early part of her career she completed a BSc in biochemistry at the University of Waterloo and an MSc in biomedical sciences and toxicology at the University of Guelph. Following this, she obtained a PhD in pharmacology and toxicology at the University of Toronto under the supervision of Dr J Peter McPherson. Her project, which introduced her to mechanisms of genomic stability and DNA repair, focused on the characterisation of a novel mouse model of the disease Fanconi Anemia. More recently, Meghan specialised further by pursuing a postdoctoral position with Dr Stephen West at Clare Hall Laboratories, Hertfordshire, latterly part of the Francis Crick Institute, London. Her project focused on the role of structure specific endonucleases in the formation of chromothriptic chromosomes originating from micronuclei. Meghan is excited to now be part of the Dion lab and aims to apply her knowledge of genomic stability and mechanisms of DNA repair to the study of trinucleotide repeat disorders.
Antoine Mangin (Staff PhD Student) obtained his master’s degree in Paris at EPHE in 2019. During this time, he worked for 2 years in the laboratory of Dr Genevieve Gourdon at Imagine Institute in Paris and also 5 months in our lab in Lausanne. His first study was about repeat size and content in atypical DM1 families. He then studied the mechanism of contraction of expanded triplet repeats. He's has been a Senior technician since Oct. 2019, but is set to start a PhD in the lab in January of 2020. He will be developing new tools to promote contractions of expanded triplet repeats.
Romane Mizeret (Master's student) obtained her BSc in Biology in July 2018 and started her MSc in September 2018 at the University of Lausanne, she is currently doing her master project in the lab. She works on understanding the influence of polymerases on repeat instability and repeat contractions. She hopes to obtain her MSc in Molecular Life Science in April 2020.
Alvaro Murillo (Postdoc / Research Associate) obtained his bachelor in biology at the University of Salamanca, with specialization in fundamental biology and biotechnology. After that, he obtained his master’s degree in Cancer Biology in 2014 at the same university. For 3 years he worked on autophagy activation to remove Huntington´s disease cell aggregates. Later, he started his PhD project under the direction of Isabel Perez-Otano and Sonia Marco at the University of Navarra for two years. The lab then moved to the Neuroscience Institute of Alicante. His project focused on in vivo silencing of GluN3A-containing NMDAR by striatal AAV-shRNA injection witch rescue HD symptoms. Also he studied deeply the expression of GluN3A in neuronal network refinement critical period. Alvaro joined Vincent's laboratory in February 2020 where he is very enthusiastic to apply and increase his knowledge of CAG/CTG repeat diseases. He hopes dominate gene editing as much as old-Spanish language.
Emma Randall (Senior Technician) obtained her BSc in Biology and then MRes in Ecology, Evolution and Conservation at Imperial College London. She went to take on the world of insecticide resistance as a research assistant at Rothamsted Research, then at the University of Exeter. In April 2019, she was warmly welcomed into the fold of the Dion lab at Cardiff University.
Gustavo Ruiz Buendia (PhD Student) did his undergraduate studies in Genomic Sciences at the National Autonomous University of Mexico. During that period, he spent a year in Cold Spring Harbor Lab in the group of David Spector, near the unparalleled NYC. After a Master’s in the lab, he has been a PhD student since Feb 2016. If he could go back in time, he would like to be a professional tennis player. Until that’s feasible, he’s delighted to investigate the wonderful world of nuclear organization!
Former lab members
PhD students:
Bin Yang: Oct. 2013 to Sept 2018 – now a consultant for Alcimed GmbH in Cologne, Germany.
Cinzia Cinesi: March 2015 to June 2019 - now a postdoc at the University of Lausanne (CH).
Postdocs:
Oscar Rodriguez Lima: May 2016 to August 2018 – now a trainee with Bart Deplancke at the EPFL (CH).
Master Students:
Antoine Mangin – Sept. 2018 to Jan 2019 – now completing his MSc - co-direction with Stéphanie Tomé at Institut Imagine (FR).
Dinis Barros - Feb 2018 to May 2019 - now a PhD student with Jolanda van Leeuwen at UNIL (CH).
Nastassia Gobet - Feb. 2017 to May 2018 - now a PhD student with Paul Franken at UNIL (CH).
Paula Barszcz – Feb. 2016 to Jan. 2017 – now a Junior Front-end Developer with APPLICA.AI in Warsaw, Poland.
Alicia Borgeaud – Feb. 2016 to May 2017 – now a PhD student with Wanda Kukulski at the LMB in Cambridge, UK.
Evgeniya Trofimenko – Feb. 2015 to Jan. 2016 – now a PhD student with Christian Widman at UNIL (CH).
Gustavo Ruiz Buendia - Feb. 2015 to Jan 2016 - now a PhD student in our lab.
Cinzia Cinesi - Feb. 2014 - Jan 2015 - now a Postdoc in our lab.
Undergraduate Students:
Romane Mizeret – Aug. to Sept. 2017 and Aug. to Sept 2018 – now a Master student in our lab - registered at UNIL (CH).
Johanna E. Martin – Jul. to Aug. 2016 – now a PhD student with Karim Labib at the University of Dundee (UK).
Waad Al-Bawardi – Jul. to Aug. 2014 – now a PhD Student with Nick Gilbert at the University of Edinburgh (UK).
Others:
Karim Bouvet - Research Assistant from Oct 2018 to Sept 2019 - now looking for new opportunities.
Flavia Marzetta - Bioinformatician from June 2017 to June 2018 - now part of the Swiss Institute of Bioinformatics.
Lorène Aeschbach – Senior Technician from Dec. 2013 to Jan 2019 – now a senior technician in Hilal A. Lashuel at the EPFL (CH).
Antonia Feola – Visiting PhD student from Oct. to Dec. 2014 – now a Scientific Researcher at Università degli Studi di Napoli Federico II (IT).
Marie Sgandurra – Research Assistant from Dec. 2013 to Jun. 2014 – now a Lead Laboratory Technician with Philip Moris International (CH).
