CV Science

LAURENCE AMAR PhD Molecular Genetics, HDR

Course and current status

EDUCATION and TRAINING 

UNIVERSITIES PARIS-7 and PARIS-11 (FRANCE)

1999: HDR (Habilitation to Conduct Scientific Research)

1990: PhD, Molecular Genetics

STATUS

 Chargé de Recherche Hors Classe CNRS

Scientific summary

RESEARCH SUMMARY

I have been working on genetic and epigenetic controls of genome expression in eukaryotes from my PhD thesis to the present time. First, in mammals, then in ciliates, eventually in mammals. For the last years I have mainly been involved in the world of non-coding RNAs, high-throughput technologies and DOHaD concept. I have in particular developed an approach aimed at 
characterizing controls mediated by microRNAs (miRNAs) in vivo. 

miRNAs are RNA molecules of 20-24 bases that control gene expression. In metazoan, miRNA-mediated controls are mainly post-transcriptional and result from interactions between complementary bases of miRNAs and target RNAs. As a result, translation and/or stability of mRNAs are lowered and the levels of the corresponding proteins are diminished.

Mammalian genomes harbor several hundreds of miRNA genes (miR genes), the expression of which is essential during spermatogenesis and in somatic tissues of the post-implantation embryo and adult. miR genes display developmental- and/or tissue-specific expression and different miRNA populations characterize different developmental stages and/or tissues.

Algorithms have been developed to predict miRNA-targeted mRNAs. In metazoan genomes, main criteria are complementarity between miRNA base positions 2-8 (seed regions) and mRNA 3’UTR bases. Bioinformatic analyses provide lists of hundreds of target candidates for each miRNA because of the short size of miRNA:mRNA heteroduplex and large complexity of 3’UTR transcriptomes. Each miRNA has therefore be predicted to participate in the control of the expression of several hundreds of protein-coding genes.

miRNAs have long been investigated one by one for their (over)expression and impact on the expression of protein-coding genes rather than in the context of miRNA populations. However bioinformatics analyses strongly suggest that expressions of most protein-coding genes are controlled by miRNA combinations and that miRNA populations rather than single microRNAs have to be investigated. miRNA over-expression also now appears as a source of bias for the collection of data.

High-throughput technologies developed those last years, especially the Illumina sequencing technology, open new possibilities for the investigation of miRNA populations and analysis of their impact on protein-coding gene expression. With my collaborators, I have established a strategy that allows to produce miRNA expression data of statistical significance and biological inference at a cost compatible with laboratory finances. Barcoded cDNA libraries from a high number of biological replicates are built in our laboratory using an Illumina-like protocol and individual miRNA expression profiles are constructed using the miRanalyser platform and miRBase database. We currently use this strategy to compare profiles and identify miRNAs of differential expression from several tissues of human, mouse and rat under physiological and pathophysiological conditions.

Our current goal is to characterize miRNA:mRNA interactions, in vivo, under physiological and pathophysiological conditions. miRNA research deserves specific investigation in brain because brain miRNA and mRNA populations are highly complex. We are using model miRNAs and model brain sub-structures to study miRNA:mRNA intercatomes and proteomes in conditions of miRNA differential expressions. 

Philipp Krabusch (PhD) 2015 - 2019. PhD (University Witten/Wuppertal, Allemagne). 'miRNAs as Plasma Biomarkers of Gestational Diabetes'.

Soraya Doubi – Kadmiri (M2 & PhD) 2011 - 2016. PhD (Université Paris 11). 'MiRNomes in Physiological and Pathological Status in Rattus norvegicus'.

Charlotte Benoit (PhD) 2009-2012. PhD (Université Paris 11). 
'Hypothalamic MicroRNAs and metabolic programming in Rattus norvegicus'.

Guillaume Beaumont (M2) 2011. M2 (University Paris 7)
. 'Bioinformatics Analysis of microRNA expression profiles in Rattus norvegicus”.

Chunlong Chen (PhD) 2004-2007. PhD (University Paris 11 + University Sun-Ya-Sen, Guangzhou, China). 'Non-Coding RNA Genes in the Paramecium tetraurelia' genome: Computational Identification and Evolution'.

Karine Dubrana (M2 & PhD) 1993-1999. PhD (University Paris 7).'Genetic and Molecular Analyses of Programmed DNA Excision in Paramecium primaurelia'

Anne Le Mouël (PhD) 1994-1996. PhD (University Paris 6),
'Genome Plasticity in Paramecium aurelia'.

Sandrine Chauve 1992, Eric Coic 1992, Maud Maurizon 1993, Maud Maurizon 1994, Marylin David 1996, Awa Ndiaye 1999, Gwénolé Hamonic 2001, François-Xavier Laurent 2004, Nadia Bessoltane 2005, Karima Mestaoui 2009, Aurélien Toulze 2010, Le Ki 2010, Soraya Doubi-Kadmiri 2011, David Weber 2013, Patrick Weil 2013, Côme de Saint Mathieu 2014.

TEACHING ACTIVITIES (LESSONS)

Ecole Doctorale 'Structure et Dynamique des Systèmes Vivants'. Module Biologie Expérimentale Animale et Modélisation Prédictive. 'ARN Non-Codants et Régulation de l'Expression des Génomes'. 2016, 2017.

Weil PP, Jaszczyszyn Y, Baroin-Tourancheau A, Postberg J, Amar L.* (2017) Holistic and Affordable Analyses of MicroRNA Expression Profiles Using Tagged cDNA Libraries and a Multiplex Sequencing Strategy. Methods Mol Biol. 2017;1654:179-196.

Doubi-Kadmiri S., Benoit B., Benigni X., Beaumont G., Vacher C-M., Taouis M., Baroin-Tourancheau A. and Amar L.* (2016) Substantial and robust changes in microRNA transcriptome support postnatal development of the hypothalamus in rat. Scientific Reports, 6:24896.

Baroin-Tourancheau A., Benigni X., Doubi-Kadmiri S., Taouis M. and Amar L.* (2016) Lessons from microRNA Sequencing Using Illumina Technology. Advances in Bioscience and Biotechnology, 7, 319-328.

Baroin-Tourancheau A., Benigni X., Benoit C., Doubi-Kadmiri S., Vacher CM., Taouis M. and Amar L.* (2014) Keys for microRNA expression profiling of single rat hypothalamic nuclei and multiplex sequencing strategies',  Exp. Physiol,. 99 (1) 72-77.

Benoit C., Ould-Hamouda H., Crepin D., Gertler A., Amar L., Taouis M. (2013) Early leptin blockage predisposes fat-fed rats to overweight and modifies hypothalamic microRNAs,  J Endocrinol., 218(1):35-47.

Amar L.*, Benoit C., Beaumont G., Vacher CM., Crepin D., Taouis M. and Baroin-Tourancheau A. (2012) MicroRNA expression profiling of hypothalamic arcuate and paraventricular nuclei from single rats using Illumina sequencing technology, J. Neuroscience Methods, 209(1), 134-143

Chen C-L., Zhou H., Liao J-Y., Qu L-H. and Amar L.* (2009) Genome-Wide Evolutionary Analysis of the Non-Coding RNA Genes and Non-Coding DNA of Paramecium tetraurelia, RNA, 15(4), 503-514

Chen C-L., Perasso R., Qu L-H. and Amar L.* (2007) Exploration of pairing constraints identifies a 9 base-pair core within box C/D snoRNA-rRNA duplexes, J. Mol. Biol., 369(3) ,771-83.

Chardonnet S., Decottignies P., Amar L ., Le Caer J-P., Davis S., Laroche S., Le Maréchal P. (2007) “New mortalin and histidyl tRNA synthetase isoforms point out a pitfall in proteomic analysis of Egr1-genetically modified mice”, Proteomics, 7(2), 289-98.

Amar L.* and Dubrana K.  (2004) Epigenetic control of chromosome breakage at the 5’ end of Paramecium tetraurelia gene A, Eukaryotic Cell, 3(5),  1136-1146.

Dubrana K. and Amar L.* (2001) Control of programmed DNA excision efficiency in Paramecium”, Nucl. Acids Res., 29(22), 4654-4662.

Dubrana K. and Amar L.* (2000) Programmed DNA under-amplification in Paramecium primaurelia, Chromosoma, 109 , 460-466.

Dubrana K., Le Mouel, A. and Amar L.* (1997) Deletion endpoint allele-specificity in the developmentally regulated elimination of an internal DNA sequence (IESs) in Paramecium, Nucl. Acids Res., 25 (12) , 2448-2454.

 Amar L.* (1994) Chromosome end formation and internal sequence elimination as alternative genomic rearrangements in the ciliate Paramecium,J. Mol. Biol., 236, 421-426 + corrigendum (1997) J. Mol. Biol., 265 , 465.

Amar L.C.* (1990) Doctorat de l'université Paris VII (nouvelle thèse), spécialité Biochimie, (mention très honorable), soutenu devant le jury composé des Dr. Philip Avner (directeur de recherche), Pr. Hubert Condamine (président), Dr.  Jean-Louis Guénet (rapporteur), Pr.  Claudie Isnard (examinatrice) et Pr. Jean-Louis Mandel (rapporteur) : Etude moléculaire du chromosome X murin et de la régulation de son expression.

Garchon H-J., Loh E., Ho B., Amar L.C., Avner P. and Davis M.M. (1989) Complexity of the XLR locus : a large set of closely homologous genes that comprises many pseudogenes and that is dispersed on both X and Y chromosomes,Nucl. Acids Res., 17 (23), 9871-9888.

Brockdorff N., Amar L.C. and Brown S.D.M. (1989) Pulse-field linkage of the P3 , G6pd and Cf-8  genes on the mouse X chromosome : demonstration of synteny at the physical level,Nucl. Acids Res., 17 (4), 1315-1326.

Holger P., Jendraschak E., Hauck S., Amar L.C., Avner P. and Müllhofer G. (1988) Molecular cloning and sequencing of a murine Pgk-1  pseudogene family,Gene, 71, 461 - 472.

Amar L.C., Dandolo L., Hanauer A., Ryder-Cook A.,  Arnaud D., Mandel J.L. and Avner P.R. (1988) Conservation and reorganisation of loci on the mammalian X chromosome : a molecular framework for the identification of homologous sub-chromosomal regions in man and mouse, Genomics, 2,  220 - 230.

Avner P.R.,  Amar L.C., Dandolo L. and Guenet J.L. (1988) Genetic analysis of the mouse using interspecific crosses, Trends in Genetics, 4, 18 - 23.

Anver P.R., Bishop C., Amar L.C., Cambrou J., Hatat D., Arnaud D. and Mattei M-G., (1987) Mapping the mouse X chromosome : possible symmetry in the location of sequences on the mouse X and Y chromosomes, Development, 101,   supplement , 107 - 116.

Avner  P.R., Arnaud D., Amar L.C., Cambrou J., Winking H. and Russell L.B. (1987) Characterisation of a panel of somatic cell hybrids for the regional mapping of the mouse X chromosome, Proc. Natl. Acad. Sci. USA, 84, 5330 - 5334.

Avner P.R.,  Amar L.C., Arnaud D., Hanauer A. and Cambrou J. (1987) Detailed ordering of markers localising to the Xq26- qter region of the mouse X chromosome by the use of an interspecific Mus  spretus  mouse cross. Proc. Natl. Acad. Sci. USA, 84, 1629 - 1634.

Heilig R., Lemaire C., Mandel J-L., Dandolo L., Amar L.C. and Avner P.R. (1987) Localisation of the mouse region homologous to the Duchenne Muscular Dystrophy on the mouse X chromosome, Nature, 328, 168 - 170.

Dautigny A., Mattei M-G., Morello D., Alliel P.M., Pham-Dinh D., Amar, L.C., Arnaud D., Simon D., Mattei J-F., Guenet J-L., Jolles P. and Avner P.R. (1986) The neurological defect in jimpy mice is due to a mutation in the structural gene coding for the myelin associated proteolipid protein, Nature, 321, 867 - 869.

Amar L.C. , Arnaud D., Cambrou J., Guenet J-L. and Avner P.R. (1985) "Mapping of the mouse X chromosome using random genomic probes and an interspecific mouse cross", EMBO J., 4, 3695 - 3700.

ORAL COMMUNICATIONS

L. Amar. microRNAs and clinical biomarkers. Current knowledge and future challenges. ESPGHAN Summer School in Basics and Translational Research. Cambridge, UK. July 2018. Invited Speaker.

L. Amar. microRNA populations of hypothalamic arcuate nucleus and median eminence in rat. Lack of significant influence of perinatal or adult diet/metabolism at early postnatal development stages or in adults, MicroRNAs & Editing Europe-Meeting. Cambridge, UK. November 2016. Invited Speaker.

L. Amar.microRNAs in metazoan. Kuala Lumpur, Malaisie. January 2015. Invited Speaker.

L. Amar. microARN et physiopathologie. Ecole thématique interdisciplinaire d'échanges et de formation en biologie. Porquerolles, France. April 2014.

L. Amar. Examples of microRNA expression profiling using Illumina sequencing technology. TAGp 2013 (Theoretical Approaches for the Genome and the proteins), LAPTh, Annecy le Vieux, France. November 2013. Invited Speaker.

A. Baroin-Tourancheau, X. Benigni, C. Benoit, S. Doubi-Kadmiri, C-M. Vacher, M. Taouis and L. Amar. microRNA Expression Profiling of Hypothalamic Nuclei from Single Rats using Illumina Sequencing Technology: Looking at a High-fat Maternal Diet Impact on Progeny Profiles. 10th World Congress on Neurohypophysial Hormones, Bristol, UK. July 2013. Invited Speaker.

L. Amar. Profils ‘’miRNA’’ de noyaux hypothalamiques chez le rat. Variabilité individuelle d’expression? Journée Séquençage à haut débit,  Colloque de l’ IFR115. Gif sur Yvette, France. October 2011. Invited Speaker.

L. Amar. Coding and non-coding DNA in Paramecium tetraurelia : Content and Evolution. Canton, Chine. May 2009. Invited Speaker.

Chen C-L., Zhou H., Liao J-Y., Qu L-H. and Amar L. Genome-Wide Evolutionary Analysis of the Non-Coding RNA Genes and Non-Coding DNA of Paramecium tetraurelia.4th International Meeting, GDRE Paramecium. Potzberg, Allemagne. October 2008.

Chen C-L., Zhou H., Liao J-Y., Qu L-H. and Amar L. Genome-Wide Analysis of the Non-Coding DNA of Paramecium tetraurelia. 46th Conférence du GPLF (Groupement des Protistologues de Langue Française) élargie depuis plusieurs années aux Protistologues non francophones). Séville, Espagne. Juiy 2008.

Amar L.C  and Dubrana K., IES evolution in Paramecium. Communication orale in FASEB Conference “Molecular Biology of Ciliated Protozoa". Saxton's River, Vermont, USA. August 2001. Invited Speaker.

Amar L.C  and Dubrana K. IESs, gènes d’antigène de surface et évolution. Huitième colloque Elements transposables. Strasbourg. Juiy 2000.

Amar L.C  and Dubrana K. An IES not like the others. FASEB Conference “Molecular Biology of Ciliated Protozoa”. Saxton's River, Vermont, USA. August 1999. Invited Speaker.

Amar L.C. et Dubrana K. Excision site-spécifique et formation d’extrémité chromosomique programmées chez Paramecium. Septième colloque Elements transposables. Vichy. Juiy 1998

Amar L.C., Dubrana K. and Le Mouel A. Chromosome end formation in Paramecium  species. FASEB Conference “Molecular Biology of Ciliated Protozoa”. Copper Mountain, Colorado, USA. Juiy 1997.

Amar L.C., Le Mouel A. et Dubrana K.Chromosomal ends form within region of defective internal DNA elimination in Paramecium primaurelia. FASEB Conference “Molecular Biology of Ciliated Protozoa. Copper Mountain, Colorado, USA. Juiy 1995

Amar L.C., Le Mouel A. et Dubrana K. Fragmentation chromosomique et excision de segments d’ADN sont deux modes alternatifs de réorganisation d’une même région génomique chez Paramecium primaurelia. Premier Colloque des 3R “l’ADN dans tous ses états : Réplication, Recombinaison, Réparation”. Villejuif, CIS-ARC. June 1995

Amar L.C. Internal sequence elimination versus telomere formation in Paramecium primaurelia. Gordon Research Conference “Molecular Biology of Ciliated Protozoa". Henniker, New Hampshire, USA. Juiy 1993

Amar L.C., Dandolo L., Arnaud D. and Avner P.Molecular definition of murine loci homologous to the drosophila Sex-lethal  locus. 6th International Workshop on the Molecular Genetics of the Mouse. Cambridge. Juiy 1988.

Amar L.C., Dandolo L., Arnaud D., Hanauer A., Ryder-Cook A., Mandel J.L. and Avner P. Conservation and reorganisation of loci on the mammalian X chromosome: a molecular framework for the identification of homologous sub-chromosomal regions in man and mouse". Ist International Workshop on Mouse Gene Mapping. Paris. September 1987

Amar L.C., Arnaud D., Cambrou J. and Avner P. High resolution mapping of the mouse X chromosome. 5th International Workshop on the Molecular Genetics of the Mouse. Zürich. Juiy 1986.

MEMBERSHIP

SFI : Société Française de Bioinformatique

SF-DOHaD: Société Francophone Origines Dévelopmentales de la Santé