EVOLINEProject reference: 623324
Funded under :
Mobile elements: shuffling the regulome in development and disease
Total cost:EUR 265 317,3
EU contribution:EUR 265 317,3
Topic(s):FP7-PEOPLE-2013-IOF - Marie Curie Action: "International Outgoing Fellowships for Career Development"
Call for proposal:FP7-PEOPLE-2013-IOFSee other projects for this call
Funding scheme:MC-IOF - International Outgoing Fellowships (IOF)
The present structure of the human genome is largely a result of the activity of Transposable Elements (TEs) or jumping genes. Indeed, they have constantly provided genomic variability over evolution, resulting in the generation of new genes and new regulatory circuits among others, and they are still doing it now, mainly leaded by the activity of few classes of TEs as LINE-1 retrotransposons.
LINE-1s are the only autonomous active TEs currently mobile in the human genome, and its activity has been responsible for the generation of at least half of it. Strictly, LINE-1 elements are molecular parasites as they solely replicate in our genome with evident genomic instability effects. However, the recently described activity in healthy human brain, where non-heritable (and thus non-selfish) insertions would provide some sort of genomic plasticity, stokes the discussion about their parasitic (instability) versus symbiotic character (variability, plasticity). In addition, it has been recently reported LINE-1s mobilisation in all human tumours examined to date. Whether their activity participates in the generation/promotion of cancer remains unknown.
It is established that many fixed TEs evolved as part of the regulome in a myriad of ways, like for instance becoming gene distal enhancers. However, new somatic TE insertions might impact gene expression/regulation in a mosaic manner, editing the information stored in the somatic genome in some way. In EVOLINE, I propose to conduct real time evolution experiments to infer the phenotypic consequences induced by new somatic TE insertions. Specifically, EVOLINE aims to reveal the role of TEs in the edition of the somatic genome and its effect on neuronal development and cancer.
As LINE-1s represent a third of our genome and because of their ongoing activity, deciphering the impact that new somatic TE insertions exert in the human genome will help us to understand their role in genome dynamics and their impact on human diseases.
EU contribution: EUR 265 317,3
Avda. Americo Vespucio
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