Objective
Less than 25% of patients diagnosed with acute myeloid leukemia (AML) survive longer than 5 years. Current treatment regimen are based on non-specifically acting cytotoxic drugs that cause severe side effects. More effective and more specific, targeted therapies are thus needed. Progress, however, has long been hampered by a lack of understanding of the molecular vulnerabilities of the disease.
We here propose to identify and study synthetic lethal interactions with mutations in nucleophosmin 1 (NPM1) in AML. Up to 35% of AML patients bear mutations in NPM1 leading to a localization of this nucleolar protein to the cytoplasm and a characteristic change in gene expression pattern. Moreover, NPM1 mutations appear to be driver events and stable over multiple courses of therapy and relapse. Identifying cellular pathways or proteins that are essential in an NPM1 mutated background but not in NPM1 wild type cells may thus not only contribute to a better understanding of NPM1 biology but also yield entry points for the development of drugs that selectively kill NPM1 mutated AML cells.
We will take an integrated chemical biology approach to first identify small molecules that selectively kill NPM1 mutated over NPM1 wild type cells and then elucidate their mode of action to gain insight into the underlying biology. This project thus uniquely builds on the longstanding experience of the host laboratory and institute in chemical screening, the elucidation of the mode of action of small molecules and in hematological malignancies.
The proposal is designed to complement the experienced researchers current knowledge in chemical synthesis, assay development, solid tumor biology and small animal imaging techniques to become a well-rounded chemical biologist with a disease focus on solid and liquid cancers. The hosting institution will gain from the researcher´s chemical expertise and find opportunities to expand its network of international collaborations.
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 medical biotechnology genetic engineering gene therapy
- medical and health sciences health sciences inflammatory diseases
- medical and health sciences clinical medicine gastroenterology inflammatory bowel disease
- medical and health sciences basic medicine neurology multiple sclerosis
- medical and health sciences clinical medicine oncology leukemia
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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-2015
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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.
1090 Wien
Austria
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.