Malik Lab

Malik Lab Members

Antoine Molaro

Backgroud

Antoine is originally from France. He studied Biology in Paris, at “Pierre et Marie Curie” University and “Ecole Normale Supérieure”. There he became interested in embryogenesis and more broadly heredity, topics he explored in details completing a Master degree in Developmental Biology. He obtained his Ph.D. under the mentorship of Dr. Gregory Hannon at Cold Spring Harbor Laboratory, NY, USA. His thesis work aimed at characterizing the signals triggering the deposition of heritable epigenetic marks in human and mouse reproductive cells. One such signal involves PIWI interacting RNAs (or piRNAs), a class of small interfering RNAs. His research demonstrated that silencing complexes loaded with piRNAs selectively target active retrotransposons via the sensing of their transcription in germ cells. Evolutionary biology was never far-off his mind and during his graduate studies he also explored how the genome and the epigenome influenced each other during human evolution. In particular, he focused on regions of the genome that acquired opposite methylation levels between chimpanzees and humans despite high underlying sequence conservation. Understanding how this differential recognition is achieved remains one of his current research goals, and brought him to the Malik Lab.

Research Interest

Every cell of the human body essentially possesses the same genomic information. However, in the adult, cells have differentiated functions and morphologies. These differences are the result of a coordinated process of development. Chromatin organization allows for such states to be established and maintained in any given cell lineage and constitute a layer of epigenetic information. Antoine is interested in how epigenetic information is carried across generations and how it influences genome sequence evolution and ultimately speciation.

One of the focuses of Antoine’s research in the Malik lab is to understand how silencing chromatin pathways evolve in response to the ever-changing retrotransposon repertoire of primate genomes. Polymorphic insertions and recent “invasion” by new retrotransposon families can lead to severe incompatibilities between populations and ultimately drive reproductive isolation. Host-encoded silencing factors face the evolutionary conundrum of diversifying towards new threats while keeping older insertions in check. In addition, their silencing needs to be spatially and temporally tuned so as not to affect host transcriptional networks. Antoine applies phylogeny-guided approaches in combination with high-throughput sequencing techniques to study how these evolutionary tradeoffs have shaped primate lineage specification and human genome evolution.

His second research focus is to understand the function of a family of testis-specific histone variants know as “short H2As”. Histones and their variants are some of the most slowly evolving protein in eukaryotes. This stems from their essential structural and regulatory roles during genome compaction. Surprisingly, short H2A variants are subject to accelerated evolution with some evidence for positive selection in primates. Antoine studies how rapid evolution has shaped their chromatin function and uses mouse models to understand their role during reproduction. 

 

Other Interests

When he is not sequencing genomes, Antoine’s passion is drumming. He likes to improvise in jazz bands or play hard with his friends in cover bands. He also loves epistemology, which he read avidly in French only. When not in the lab, you can usually find him listening to live music in town with his lovely wife Estelle.


Publications

Molaro A, Young JA, Malik HS. Evolutionary origins and diversification of testis-specific short histone H2A variants in mammals. Genome ResearchPublished in Advance March 16, 2018, doi:10.1101/gr.229799.117. PMID: 29549088

Qu J, Hodges E, Molaro A, Gagneux P, Dean MD, Hannon GJ, and Smith AD. (2017). Evolutionary expansion of DNA hypomethylation in the mammalian germline genome." Genome Research. 2018: 28: 145-158. PMID: 29259021

Molaro A, Malik HS. Culture Shock. Elife. 2017: 8;6. pii: e33312. PMID: 29251593

Molaro A, Drinnenberg IA. Studying the evolution of histone variants using phylogeny. Springer Methods “Histone Variants: Methods and Protocols”. 2017 – in press.

Molaro A, Malik HS. Hide and seek: how chromatin-based pathways silence retroelements in the mammalian germline. Current opinion in genetics & development. 2016; 37:51-8. PMID: 26821364

Molaro A, Falciatori I, Hodges E, Aravin AA, Marran K, Rafii S, McCombie WR, Smith AD, Hannon GJ. Two waves of de novo methylation during mouse germ cell development. Genes & development. 2014; 28(14):1544-9. PMID: 25030694

Kaaij LT, van de Wetering M, Fang F, Decato B, Molaro A, van de Werken HJ, van Es JH, Schuijers J, de Wit E, de Laat W, Hannon GJ, Clevers HC, Smith AD, Ketting RF. DNA methylation dynamics during intestinal stem cell differentiation reveals enhancers driving gene expression in the villus. Genome biology. 2013; 14(5):R50. PMID: 23714178

Fang F, Hodges E, Molaro A, Dean M, Hannon GJ, Smith AD. Genomic landscape of human allele-specific DNA methylation. PNAS. 2012; 109(19):7332-7. PMID: 22523239

Muerdter F*, Olovnikov I*, Molaro A*, Rozhkov NV*, Czech B, Gordon A, Hannon GJ, Aravin AA. Production of artificial piRNAs in flies and mice. RNA. 2012; 18(1):42-52. PMID: 22096018

Molaro A*, Hodges E*, Fang F, Song Q, McCombie WR, Hannon GJ, Smith AD. Sperm methylation profiles reveal features of epigenetic inheritance and evolution in primates. Cell. 2011; 146(6):1029-41. PMID: 21925323

Hodges E, Molaro A, Dos Santos CO, Thekkat P, Song Q, Uren PJ, Park J, Butler J, Rafii S, McCombie WR, Smith AD, Hannon GJ. Directional DNA methylation changes and complex intermediate states accompany lineage specificity in the adult hematopoietic compartment. Molecular cell. 2011; 44(1):17-28. PMID: 21924933