Project description
Complete characterisation of undefined long intervening noncoding RNAs
In 2003, the Human Genome Project, an extensive multinational collaboration and one of the most ambitious scientific endeavours ever undertaken, produced a genome sequence accounting for over 90 % of the human genome. Following decades of subsequent research, we now know that the very large part of our DNA made up of non-protein-coding regions, so-called intergenic regions, are not superfluous but play key roles in gene regulation. The European Research Council-funded lincSAFARI project will investigate the role(s) of long intervening noncoding RNAs (lincRNAs) in gene regulation during cell differentiation. The team will employ comparative genomics, quantitative molecular phenotyping and high-throughput screening along with computational biology to exhaustively describe previously uncharacterised lincRNAs.
Objective
It is now clear that many intergenic regions in eukaryotic genomes give rise to a range of processed and regulated transcripts that do not appear to code for functional proteins. A subset of these are long (>200 nt), capped and polyadenylated RNAs transcribed by RNA polymerase II and collectively called long intervening noncoding RNAs or lincRNAs. The recent estimates are that the human genome encodes >10,000 distinct lincRNAs, many of which show tissue-specific expression and are frequently dysregulated in human disease, including neurodegeneration.
Given the growing number of lincRNAs implicated in human disease or required for proper development, fundamental questions that need to be addressed are: Which lincRNAs are functional? How is functional information encoded in the lincRNA sequence? Is this information interpreted in the context of the mature or the nascent RNA? What are the identities and functional roles of specific sequence domains within lincRNA genes?
Our main hypothesis is that many lincRNA loci play key roles in gene regulation during cell differentiation, both via functionally important transcription events and post-transcriptionally, through the combined action of multiple short sequence domains. We will test this hypothesis using three complementary approaches – comparative genomics, detailed perturbations in mammalian cells followed by quantitative molecular phenotyping, and high-throughput screens for sequences able to carry out specific functions.
We propose an interdisciplinary approach combining computational, molecular and stem cell biology. Our methodology will be scalable, allowing us to tackle completely uncharacterized long RNAs and eventually zoom in and study their individual bases. Upon successful accomplishment of the program, we will delineate modes of action of numerous lincRNAs, report sequence patches that are functionally important and understand how specific bases and structures act in concert to drive lincRNA function.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences cell biology
- natural sciences biological sciences genetics RNA
- natural sciences computer and information sciences artificial intelligence computational intelligence
- natural sciences biological sciences genetics genomes eukaryotic genomes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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Call for proposal
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(opens in new window) ERC-2014-STG
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7610001 Rehovot
Israel
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