Skip to main content
Go to the home page of the European Commission (opens in new window)
English English
CORDIS - EU research results
CORDIS

Determination of physiologically relevant RNA substrate(s) and design of small-molecule inhibitors for Zα domains as potential intervention strategies for viral infections and autoimmunity

Objective

DNA/RNA molecules adopting the Z-conformation have been known to possess immunogenic properties. However, their biological role and importance has been a topic of debate for many years. The discovery of Z-DNA/RNA binding domains (Zα domains) in varied proteins that are involved in the innate immune response, such as the interferon induced form of the RNA editing enzyme ADAR1 (p150), Z-DNA binding protein 1 (ZBP1), the fish kinase PKZ and the pox-virus inhibitor of interferon response E3L, indicates important roles of Z-DNA/RNA in immunity and self/non-self-discrimination. Such Zα domain-containing proteins recognize Z-DNA/RNA in a conformation-specific manner. Recent studies have implicated these domains in viral recognition. Given these important emerging roles for the Zα domains, it is pivotal to understand the physiologically-relevant nucleic acid substrate for them. In this proposal, we propose to deduce the physiologically relevant substrates for Zα domains from ADAR1 p150 and ZBP1 employing next-generation RNA-seq methodologies. Knowledge on the biochemical and structural aspects of substrate specificity and substrate recognition by these domains would yield important insights into the specific roles these proteins play in the physiological context and would propel efforts at designing effective and specific small-molecule inhibitors against these proteins. Utilizing next-generation virtual ligand screening approaches and high-throughput experimental screening, efforts would be undertaken to discover potential binders/inhibitors of these domains. Small-molecule inhibitors of this domain have potential applications in anti-viral treatments especially against viruses such as influenza and human immunodeficiency virus that have huge human and economic impact as well as in the treatment of autoinflammatory disorders.

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.

You need to log in or register to use this function

Keywords

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.

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.

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.

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

See all projects funded under this funding scheme

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2017

See all projects funded under this call

Coordinator

FUNDACAO CALOUSTE GULBENKIAN
Net EU contribution

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.

€ 160 635,60
Total cost

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.

€ 160 635,60
My booklet 0 0