Objective
Rheumatoid Arthritis (RA) and Crohn’s disease (CD) are two common chronic autoimmune and complex diseases where individual susceptibility is determined by a combination of environmental and genetic factors. Almost all of the ~100 risk alleles discovered through recent genetic studies fall in non-coding region and have an elusive function. We hypothesize that risk alleles impact gene regulation by altering regulatory elements (e.g. enhancers) controlling the expression levels of genes within the same pathogenic pathway. The cell-specific variation in regulatory element (RE) activity can be identified by assaying histone modifications which correlate with chromatin states and DNA accessibility. Recently, assaying these histone modifications has become possible with ChiP seq methods, which applies high-throughput sequencing to identify genomic segments bound to antibodies to specific histone modifications. However to identify the REs impacted by risk loci, it is first necessary to determine the cells type (CT) affected by these risk loci; these cell types are not obvious in autoimmune diseases. Exploiting data on genome-wide histone marks in a library of immune-CT, we will develop a statistical method to identify the likely key pathogenic cells type by looking for immune-CTs specifically enriched in active REs containing risk loci. Subsequently, we will develop an approach to determine the cell specific REs impacted by risk loci and establish putative regulatory variant within of REs and associated with these complex disorders. I will develop this approach in my Outgoing Host Institute (Harvard Medical School) using RA as model, and will then apply it to CD in my Return Host Institute (University of Liege) where I pursue my research on the effect of regulatory risk alleles on the cell specific gene expression. This proposal will allow the discovery of new drug targets that can ultimately result in novel specific therapies for RA and CD patients.
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.
- medical and health sciences clinical medicine rheumatology
- natural sciences biological sciences genetics DNA
- medical and health sciences basic medicine immunology autoimmune diseases
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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.
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.
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.
FP7-PEOPLE-2011-IOF
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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.
Coordinator
4000 LIEGE
Belgium
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.