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Team Gael CRISTOFARI

Presentation



Basic Research Team  « Retrotransposons and genome plasticity »


Dr Gaël CRISTOFARI, CR1 INSERM, Team Leader



Presentation

100804-human-genome-composition-us

The abundance of transposable elements in the human genome was one of the most surprising and disconcerting discoveries of genomics.

More than 40 % of our DNA is made of mobile genetic elements, also called “jumping genes” (see Fig.1).

Human retrotransposons (LINE-1 and Alu) and human endogenous retroviruses (HERVs) are highly repetitive and dispersed sequences, which account for half of our DNA.

They can proliferate through an RNA-mediated copy-and-paste mechanism, called retrotransposition (see Fig. 2).

This process can drive profound genome rearrangements. It plays a central role in the plasticity of mammalian genomes and in human genome diversity. Although generally silent, retrotransposons are expressed in germ cells, in the early embryo, and in embryonic stem cells, which occasionally results in genetic diseases.

They are also massively re-expressed in the large majority of cancers. However the importance and consequences of retrotransposition on human health have been poorly studied, mostly due to difficulties in tracking new insertion events in clinical samples. Indeed it is extremely difficult to detect a new copy in a new locus among the hundreds of thousands copies inherited from our parents.

Research Project

Research Project


The questions we wish to address in our group are the following :

(i) What cellular pathways control retrotransposon copy number ? We combine functional genomics and proteomics approaches to identify positive and negative regulators of retrotransposition in humans.

(ii) What are the molecular mechanisms of retrotransposons replication ? We develop in vitro assays containing the complete retrotransposition machinery to study step-by-step this mutagenic process.

(iii) How retrotransposons participate in the policenormal and pathological remodeling of the human genome ? To this purpose we are currently developing innovative approaches using next-generation sequencing technologies and bioinformatics to track retrotransposition events in clinical samples, especially in tumor samples.

Understanding how the activity of retrotransposons is controlled will impact our knowledge of the mechanisms that lead to new genetic diseases or to cancer progression. Since mobile genetic elements are becoming important tools in insertional mutagenesis or gene-transfer technologies in mammals, our work should also help to improve and widen the use of retrotransposons in mammalian functional genomics or gene-therapy.

Press Articles


The french magazine "La Recherche" published in June 2015 a report on young scientists "under 40 and representing the scientific future of the french research" (La Recherche, N° 500, Juin 2015). Among these scientists, Gaël Cristofari, Team leader at the IRCAN Institute, was cited.




Research Team

Research Team

cristofari_team_2014
From left to right :Tania, Ashfaq, Natacha, Nadira (hiding behind), Ramona, Gael, Jorge (hiding behind), Claude, Sebastien, Javier


RESEARCH TEAM


CRISTOFARI Gaël, CR1 INSERM, Team Leader

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DESNUELLE Claude, PU-PH CE

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SACCONI Sabrina, PU-PH2

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DOUCET Aurélien, CR2 CNRS

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CONTET Julian, CDD AI UNS

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PHILIPPE Claude, IE1 CNRS

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GALANTONU Ramona, PhD Student

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SULTANA Tania, Phd Student Erasmus

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DOUFOUNDOU Carlette, Phd Student

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ROPERT Baptiste, Master 1 INSERM

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Publications


Publications


2016


Goic B, Stapleford KA, Frangeul L, Doucet AJ, Gausson V, Blanc H, Schemmel-Jofre N, Cristofari G, Lambrechts L, Vignuzzi M, Saleh MC.

Virus-derived DNA drives mosquito vector tolerance to arboviral infection.

Nat Commun. 2016 Sep 1;7:12410.



C Philippe, DB Vargas-Landin, AJ Doucet, D Van Essen, J Vera-Otarola, M Kuciak, A Corbin, P Nigumann, G Cristofari

L'activation des instances de rétrotransposon L1 individuels est limitée à la cellule de type loci permissive dépendante.

eLife, Mars 2016; 10,7554 / eLife.13926


2015


Albrengues J, Bertero T, Grasset E, Bonan S, Maiel M, Bourget I, Philippe C, Herraiz Serrano C,

Benamar S, Croce O, Sanz-Moreno V, Meneguzzi G, Feral CC, Cristofari G, Gaggioli C.

Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts.

Nat Commun. 2015, Dec15;6:10204.


Marsaud A, Dadone B, Ambrosetti D, Baudoin C, Chamorey E, Rouleau E, Lefol C,

Roussel JF, Fabas T, Cristofari G, Carpentier X, Michiels JF, Amiel J, Pedeutour F.

Dismantling papillary renal cell carcinoma classification: The heterogeneity of genetic

profiles suggests several independent diseases.

Genes Chromosomes Cancer, 2015, Jun;54(6):369-82.


Mir AA, Philippe C, Cristofari G.

euL1db: the European database of L1HS retrotransposon insertions in humans.

Nucleic Acids Res., 2015 Jan;43:D43-7.


2014


Viollet S, Monot C, Cristofari G.

L1 retrotransposition : The snap-velcro model and its consequences.

Mob. Genet. Elements, 2014, Jan 1;4(1):e28907.


2013

Monot C*, Kuciak M*, Viollet S, Mir AA, Gabus C, Darlix JL, Cristofari G.

The specificity and flexibility of l1 reverse transcription priming at imperfect T-tracts.

PLoS Genet., 2013, May;9(5):e1003499.


Sauerwald A, Sandin S, Cristofari G, Scheres SH, Lingner J, Rhodes D.

Structure of active dimeric human telomerase.

Nat. Struct. Mol. Biol., 2013, Apr;20(4):454-60.


Goic B, Vodovar N, Mondotte JA, Monot C, Frangeul L, Blanc H, Gausson V,

Vera-Otarola J, Cristofari G, Saleh MC.

RNA-mediated interference and reverse transcription control the persistence of RNA viruses

in the insect model Drosophila.

Nat. Immunol., 2013, Apr;14(4):396-403.


2012

Ainouche A, Bétermier M, Chandler M, Cordaux R, Cristofari G, Deragon JM, Lesage P,

Panaud O, Quesneville H, Vaury C, Vieira C, Vitte C.

International Congress on Transposable Elements (ICTE) 2012 in Saint Malo and

the sea of TE stories.

Mob. DNA., 2012, Oct 30;3(1):17.


Vidale P, Magnani E, Nergadze SG, Santagostino M, Cristofari G, Smirnova A, Mondello C,

Giulotto E.

The catalytic and the RNA subunits of human telomerase are required to immortalize

equid primary fibroblasts.

Chromosoma., 2012, Oct;121(5):475-88.


Chaurasiya KR, Geertsema H, Cristofari G, Darlix JL, Williams MC.

A single zinc finger optimizes the DNA interactions of the nucleocapsid protein of the

yeast retrotransposon Ty3.

Nucleic Acids Res., 2012, Jan;40(2):751-60.


2010

Abreu E, Aritonovska E, Reichenbach P, Cristofari G, Culp B, Terns RM, Lingner J,

Terns MP.

TIN2-tethered TPP1 recruits human telomerase to telomeres in vivo.

Mol. Cell. Biol., 2010, Jun;30(12):2971-82.


2008

Kurth I, Cristofari G, Lingner J. (2008)
An affinity oligonucleotide displacement strategy to purify ribonucleoprotein complexes
applied to human telomerase.
Methods Mol Biol., 2008;488:9-22.

2007

De Cian A, Cristofari G, Reichenbach P, Delemos E, Monchaud D, Teulade-Fichou MP,
Shin-ya K, Lacroix L, Lingner J, & Mergny JL.
Re-evaluation of telomerase inhibition by quadruplex ligands and their mechanisms of action.
Proc. Natl Acad. Sci. USA., 2007;104(44):17347-17352.

Cristofari G, Reichenbach P, Regamey PO, Banfi D, Chambon M, Turcatti G, Lingner J.
Low- to high-throughput analysis of telomerase modulators with Telospot.
Nat. Methods, 2007;4(10):851-853.

Cristofari G, Adolf E, Reichenbach P, Sikora K, Terns RM, Terns MP, Lingner J.
Human telomerase RNA accumulation in Cajal bodies facilitates telomerase recruitment
to telomeres and telomere elongation.
Mol. Cell., 2007;27(6):882-889.

Cristofari G, Sikora K, Lingner J.

Telomerase unplugged.

ACS Chem Biol, 2007, Mar20;2(3):155-8. Review.


2006

Cristofari G, Lingner J.
Telomere length homeostasis requires that telomerase levels are limiting.
EMBO J., 2006, 25(3):565-74.

2004

Cristofari G, Ivanyi-Nagy R, Gabus C, Boulant S, Lavergne JP, Penin F, Darlix JL.

The hepatitis C virus Core protein is a potent nucleic acid chaperone that directs

dimerization of the viral (+) strand RNA in vitro.

Nucleic Acids Res. 2004, May11;32(8):2623-31.


2003


Cristofari G, Lingner J.

Fingering the ends: how to make new telomeres.

Cell, 2003, May30;113(5):552-4.


2002



Cristofari G, Darlix JL.

The ubiquitous nature of RNA chaperone proteins.

Prog Nucleic Acid Res Mol Biol., 2002;72:223-68.


Cristofari G, Bampi C, Wilhelm M, Wilhelm FX, Darlix JL.

A 5'-3' long-range interaction in Ty1 RNA controls its reverse transcription

and retrotransposition.

EMBO J., 2002, Aug15;21(16):4368-79.


(Feb 2016)




Financial Grants

Financial Grants


INSERM

Open Positions


Open positions


If you are interested in joining the Cristofari lab, for a postdoc, a PhD work or an internship, don't hesitate to directly contact Gael Cristofari at: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

 

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