Objective
Chronic hepatotropic infections including hepatitis B (HBV) and C (HCV) are a major public health
concern. Even though both viruses belong to completely distinct families the pathogenesis they elicit is
strikingly similar, leading to liver fibrosis and cirrhosis. Treatment for HBV and HCV consists of either
direct-acting antivirals or pegylated interferon (IFN)α. In contrast to HCV, these treatment regimen are noncurative
for HBV. Little is known to date about the host/pathogen interactions determining viral persistence.
Both viruses are sensitive to IFN, activating the JAK/STAT signalling pathway to activate interferonstimulated
gene expression (ISG), which are ultimately acting as antiviral immune effectors. Nevertheless,
neither type I or III IFN are very effective in their treatment.
Here, we suggest investigating the mechanistic details of type I and type III IFN action on HCV and
HBV in vitro and vivo with the goal of uncovering not only the differential ISG induction but furthermore
characterise viral immune evasion strategies. Building on our previous success in dissecting the host
response to HCV and creating the first immunocompetent mouse model for HCV we aim at using both,
novel microfluidic culture systems based on 3D hepatocyte cultures susceptible to both HCV and HBV as
well as human liver-chimeric mice in combination with single-cell analysis of the antiviral response against
HBV and HCV elicited by type I and III IFN. Additionally, we will utilize lentiviral high throughput
screening used previously for HCV to identify interferon effector molecules active against HBV. This project
will not only provide new insights into the innate immune response to chronic hepatotropic virus infections
but furthermore holds the potential of uncovering novel drug targets, aiding in the curative therapy for both,
HCV and HBV and offer novel insights into vaccine design.
This project has the aim of identifying novel host factors and drug targets enabling the development
of immunomodulatory antiviral drugs. This ranks the scope of the proposal between LS6 Immunity and
Infection and LS9 Applied Life Sciences and Non-Medical Biotechnology. Evaluating novel bioengineered
human liver culture systems and building on human liver-chimeric mice clearly places this proposal at the
forefront of identifying novel drug targets and assisting in the development of novel biotechnology and
preclinical projects.
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.
- medical and health sciences health sciences infectious diseases DNA viruses hepatitis B
- medical and health sciences health sciences infectious diseases RNA viruses hepatitis C
- medical and health sciences basic medicine immunology
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antivirals
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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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
ERC-STG - Starting Grant
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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) ERC-2014-STG
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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.
SW7 2AZ LONDON
United Kingdom
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.