© copyright Auyeung/Vincent /2013

Alena ShkumatavaUnité de génétique et biologie du développement (UGBD) - Institut Curie / CNRS / INSERM / Sorbonne Universités

ATIP-Avenir
Regulatory noncoding RNAs in normal physiology and disease

Mes recherches

Originally from Belarus, I studied at the University of Vienna (Austria) where I obtained my Master degree in biology. I did my PhD at EMBL Heidelberg (Germany) and a postdoctoral training at the Whitehead Institute for Biomedical Research/MIT (Cambridge, USA). During my postdoc, I became interested in the roles of regulatory noncoding RNAs in vertebrate development. In 2012, I received the ATIP-Avenir award to investigate the functions and molecular mechanisms of action of regulatory long noncoding RNAs (lncRNAs) in normal physiology and disease. Supported initially by the ATIP-Avenir award, I am leading a research group at Institut Curie since 2013. These first critical years supported first by the ATIP-Avenir award and then by several other grants including a starting ERC award lead to key discoveries my team has made in the RNA field. Moreover, we have developed a novel breakthrough technology for the identification of RNA-protein interactions that may be used as a drug discovery platform.

Mon projet ATIP-Avenir

Function, Mechanism and Evolution of Vertebrate Long Intervening Noncoding RNAs (lincRNAs).

One of the most puzzling observations derived from the whole genome sequencing is that the majority of the genome is transcribed, generating large numbers of noncoding RNAs. Noncoding RNAs comprise a diverse group of transcripts including small noncoding RNAs and long noncoding RNAs. While small noncoding RNAs are known to have important regulatory roles during normal development and disease, the role of long ncRNAs remains enigmatic.

Thousands of long intervening noncoding RNAs (lincRNAs) have recently been identified in mammals. To better understand function and evolution of this enigmatic class of ncRNAs, we identified over 550 lincRNAs in zebrafish. Although zebrafish lincRNAs shared common features with mammalian lincRNAs, only a few of them showed detectable sequence similarity with putative mammalian orthologs. We demonstrated that two lincRNAs are required for proper embryonic development, in particular for brain morphogenesis and neurogenesis. Remarkably, lincRNA functionality was retained in mammalian orthologs despite limited sequence conservation. My research proposal focuses on the identification and characterization of novel mechanisms of gene regulation by lincRNAs using primarily zebrafish as a model system. The majority of tested lincRNAs are expressed in different parts of the developing CNS in zebrafish embryos. Thus, I am particularly interested in investigating the role of vertebrate lincRNAs during the establishment of cellular complexity in the nervous system. My specific objectives can be divided into three major goals:

(1) define biological functions of lincRNAs during development,

(2) determine molecular and biochemical mechanisms, by which lincRNAs function,

(3) investigate the origin and evolution of vertebrate lincRNA genes.

My project will find new molecules and mechanisms that could shed light on organismal complexity and uncover new layers of gene regulation in vertebrates

Alena Shkumatava est également lauréate ERC Starting Grants 2013