Objective
HIV infections cause 1.2Mi deaths/year worldwide at steadily-increasing rates, partly because of antiretroviral resistance and the impossibility of eradicating latent viruses. To expand our understanding of HIV pathogenesis, we need to unravel all molecular mechanisms involved in HIV progression. Large viral and human RNAs are emerging as key players in HIV infection. To characterize such RNAs, I will employ an integrated structural biology approach complemented by biochemical and functional assays in vitro and in vivo and I will address two fundamental questions:
1. How does the structure of HIV genomic RNA regulate HIV infectivity?
HIV genomic RNA regulates nuclear export, packaging, splicing, and translation of viral proteins. 3D structures are known for short motifs (<200 nt), e.g. TAR and RRE. Such motifs are part of 11 larger domains (>400 nt), whose structures are unknown but conserved across HIV strains suggesting functional importance. We will study domain 2 (450 nt), which encompasses the gag-pol frameshifting motif and is crucial for correct protein synthesis. Our work will offer unprecedented insights into the structural complexity of the genome of an RNA virus.
2. How does the structure of human long non-coding RNAs (lncRNAs) affect the host-cell response to HIV infection?
HIV infections alter expression of human lncRNAs, e.g. HOTAIR, which regulate Polycomb chromatin remodeling enzymes, e.g. PRC1/PRC2, favoring epigenetic silencing and latency of HIV genes. Interactions between HOTAIR and PRC1/PRC2 are not well characterized at the molecular level. We will study HOTAIR domain 1 (530 nt), which interacts with PRC1/PRC2 and regulates their cellular action. Such work will reveal novel mechanisms of epigenetic gene-silencing that induce HIV latency.
By revealing molecular details of HIV and human RNAs, our study will enrich our understanding of HIV infectivity, potentially opening new ways for future therapies against RNA viruses.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology virology
- medical and health sciences health sciences infectious diseases RNA viruses HIV
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences molecular biology structural biology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
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.
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.
Funding Scheme
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2016
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
69117 Heidelberg
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.