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You are hereUNIL > Center for Integrative Genomics > Research > Research groups > Prof. Dion

Vincent Dion, SNF Professor

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 laboratory of David H. Evans at the University of Guelph (Canada), where he got a B.Sc. in 2002. 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, a 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 CIG in 2013 as an assistant professor with the support of a professorship from the Swiss National Science Foundation. Since then, 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.

Keywords: DNA repair, chromatin, genome stability, neurodegenerative diseases, nuclear organization.

Research summary

Because we breathe oxygen and that most of our body is made out of water, our DNA is being damaged at a rate of about 100 000 lesions per cell per day. This enormous amount of damage must be repaired efficiently and accurately if the genetic information contained in the genome is to be maintained. This fundamental process of DNA repair is the focus of the laboratory.

Mutations in several DNA repair genes greatly increase cancer predisposition and the malfunction of several caretakers of the genome lead to neurological disorders (1). These observations highlight the importance of maintaining genome stability for human health.

Each and every cell in our body contains 2 meters worth of DNA that needs to be packaged into a nucleus of about 20 to 50 micron in diameter. To put this in perspective, a micron is 1/1’000’000 of a meter and a human hair is about 100 micron wide. To achieve this packaging, DNA is wrapped around histone octamers to form nucleosomes and higher-order chromatin structures. Chromatin therefore helps to package the genome. Additionally, it provides great opportunities for the regulation of DNA-based events since nucleosomes can mask the binding site of many DNA binding proteins. This interplay between chromatin structure and DNA metabolism has been extensively studied in the context of transcription, but much less is known about its impact on DNA repair.

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To study how chromatin affects DNA repair events, our laboratory focuses on tandem repeats composed of pure stretches of CAG or CTG trinucleotides. These loci are hotspots for genome instability and the size of the repeat can expand greatly, in some cases reaching thousands of trinucleotides at a single locus. The instability depends primarily on the normal activity of DNA repair on an unusual DNA sequence. As the repeat tract gets longer, it becomes more unstable and adopts chromatin configurations that bear many of the hallmarks of dense heterochromatin (2). These characteristics make trinucleotide repeats an ideal paradigm to explore the relationship between genome stability and chromatin structure at endogenous loci. We use a combination of cutting-edge molecular biology, genetics, and genomics in human cells, including patient-derived induced pluripotent stem cells, to identify new players in trinucleotide repeat instability and to study the effects of chromatin structure and organization on DNA repair. Specifically, we have projects asking the following questions:

  1. Do chromatin modifiers affect repeat instability directly by changing the local structure of the expanded repeat tract? Many chromatin modifying enzymes have been implicated in repeat instability but their exact role is unclear. This is because every study conducted so far includes loss of function experiments that do not permit the differentiation a local effect on chromatin structure or indirect causes, such as changes in transcription genome-wide. Here we have designed novel molecular assays to address the roles of chromatin modifying enzymes in repeat instability.

  2. What is the impact of nuclear organization on trinucleotide repeat instability? Here we aim to determine whether expanded trinucleotide repeats impact their 3D organization in the nucleus and whether this organization in turn influences their repair and thus their instability.

  3. Can we induce CAG repeat contractions without also inducing expansions? This project is especially relevant to human health. Indeed, the expansion of trinucleotide repeats cause a number of neurological and neuromuscular disorders, including Huntington disease, myotonic dystrophy, as well as several spinocerebellar ataxias. All of these disorders remain without a cure. Inducing contractions would, in theory, remove the underlying cause of the disease and provide a therapeutic avenue. This project, therefore, is focused on finding conditions or treatments that specifically contract the repeat tracts and that would therefore alleviate the molecular symptoms. We have recently shown (3) that the CRISPR-Cas9 nickase can be targeted to the expanded repeat tract and induces almost exclusively contractions (Fig. 1), which is an exciting first step towards the development of gene editing approaches for therapeutic purposes.

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A long term goal of our research is to understand the mechanism of trinucleotide repeat instability such an extent that we can manipulate it at will and induce repeat contractions in patients. We are especially interested in being able to manipulate local chromatin structure to change the bias in repeat expansion usually seen in human patients.

References:

  1. Dion, V. (2014) Tissue specificity in DNA repair: lessons from trinucleotide repeat instability. Trends Genet, 30, 220-229.
  2. Dion, V. and Wilson, J.H. (2009) Instability and chromatin structure of expanded trinucleotide repeats. Trends Genet, 25, 288-297.
  3. Cinesi, C., Aeschbach, L., Yang, B. and Dion, V. (2016) Contracting CAG/CTG repeats using the CRISPR-Cas9 nickase. Nat Commun, 7, 13272.

For a full list of publications, see the ‘publications’ section of this webpage 

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Publications

 
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Lorène Aeschbach obtained her CFC from the Hôpitaux Universitaires de Genève in 2004. Before joining the lab as a technician in Dec of 2013, she worked at the CHUV and at the EPFL.

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Alicia Borgeaud obtained her bachelor of Biology at the University of Lausanne. She is currently an intern after having done her Master’s thesis in the Dion lab from Feb. 2016 to Jan. 2017. In our Lab, she is studying the role of histone deacetylases in the expansion of trinucleotide repeats. She obtained the prestigious Prix de Faculté for the best Master’s thesis in life Sciences. Beside her studies, she plays the flute and is preparing a bachelor grade in music.

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Cinzia Cinesi obtained her Bachelor in Biology from the Università dell'Insubria in Varese in 2013, where she did her research thesis on Phylogenetic characterization of Salmo trutta macrostigma in SIC Monte Arcosu, in the lab of Serena Zaccara. After a First step Master’s project in the lab of Nouria Hernandez, she joined our group in Feb 2014 for her full Master’s research project. In March 2015, she stayed on as a PhD student.

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Vincent Dion received his PhD from the Department of Biochemistry and Molecular Biology at Baylor College of Medicine (Houston, USA) for his work on the interplay between trinucleotide repeat instability and DNA methylation under the supervision of John H. Wilson. From 2008 to 2013, he undertook postdoctoral training in the laboratory of Susan M. Gasser at the Friedrich Miescher Institute (Basel, Switzerland). There, he uncovered novel roles for chromatin remodeling enzymes, recombination factors, and for the DNA damage response in chromatin mobility. Vincent joined the CIG as a Swiss National Foundation Professor in October 2013.

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Nastassia Gobet obtained her Bachelor's degree in biochemistry from the University of Geneva. She joined our group in February 2017 as a Master's student in Molecular Life Sciences with specialization in bioinformatics. She is working on a novel method to measure the instability of disease-causing trinucleotide repeats using next-generation sequencing.​

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Oscar Rodríguez Lima obtained his PhD from the National Autonomous University of Mexico under the supervision of Abraham Landa at the Medicine School. His thesis focused on the characterization of transcription factors and core promoter elements present in Taenia solium genes. He is huge fan of Song of ice and fire, Star Wars and Spiderman. He joined Dion Lab in May 2016 and is interested in the interplay between chromatin organization and remodeling and transcription of expanded CAG/CTG repeats.​

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Gustavo Ruiz Buendia 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!

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Bin Yang did her Master’s project in the Institute of Brain Science in Fudan University, Shanghai, China. During that time, she focused on the molecular mechanisms underlying nervous system development and behavior in the Zebrafish Danio rerio. On October 1st 2013, she joined the group as a PhD student. She is studying whether chromatin modifiers work locally at expanded trinucleotide repeats to affect instability.

 

Former lab members

Master Students:
Paula Barszcz – Feb. 2016 to Jan. 2017 – now a Research Technician at the International Institute of Molecular and Cell Biology in Warsaw (Poland).
Alicia Borgeaud – Feb. 2016 to May 2017 – now a PhD student at the LMB in Cambridge.
Evgeniya Trofimenko – Feb. 2015 to Jan. 2016 – now a PhD student with Christian Widman (UNIL).

Undergraduate Students:
Johanna E. Martin – Jul. to Aug. 2016 – now an undergraduate at the University of Aberdeen (UK).
Waad Al-Bawardi – Jul. to Aug. 2014 – now a Master Student in Nick Gilbert’s laboratory at the University of Edinburgh (UK).

Other:
Antonia Feola – Visiting PhD student from Oct. to Dec. 2014 – PhD with Antonio Porcellini at the Università degli Studi di Napoli Federico II (Italy) as of July 2015.
Marie Sgandurra – Research Assistant from Dec. 2013 to Jun. 2014 – now a Senior Technician with Philip Moris International.

 

Current funding:

Swiss National Foundation Professorship extension – Oct. 2017 – Sept. 2019

Novartis Stiftung für medizinisch-biologische Forschung – June 2017 – May 2018

Swiss National Foundation Professorship – Oct. 2013 to Sept. 2017

Gebert Rüf Stiftung – Rare Disease Grant – Feb. 2015 to Oct. 2017

 

 

Scholarships, Fellowships, and Prizes obtained by lab members:

Prix de Faculté – to Alicia Borgeaud for the best Master’s thesis in life sciences 2015-2017

Genesuisse Researcher of the Month – To Vincent Dion Nov/Dec 2016

ISREC Foundation – to Johanna Martin summer 2016

ISREC Foundation – to Waad Al-Bawardi summer 2014

Undergraduates wanting to spend time in the lab should first look up the SUR program whereas potential Master’s students are directed to the UNIL Master’s program.

Although there is no position currently open, we are always on the lookout for outstanding PhD students and Postdocs who have or can attract their own fellowships.

 

Guidelines to writing a cover letter (not just applicable to my lab)

– 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 two big questions:

  1. 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 and hoping that something will stick.

  2. 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.

Quality and care in a letter will take you time, but it will make an enormous difference: many fewer of your 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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Contact

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Vincent Dion

vincent.dion@unil.ch

Tel: +41 21 692 3901

 

Administrative assistant

Nathalie Clerc
nathalie.clerc@unil.ch
Tel: +41 21 692 3920

CH-1015 Lausanne  - Switzerland  -  Tel. +41 21 692 22 00  -  Fax +41 21 692 22 11
Swiss University