Objective
Cancer is the activation of dysfunctional pathways leading to abnormal behaviour of cells. A hallmark of cancer is genomic instability, triggered by a range of DNA lesions such as 8-oxo-G, caused by reactive oxygen species (ROS). ROS are generated by the cell’s metabolism and are crucial for its homeostasis. However, excessive ROS levels can induce DNA lesions resulting in increased mutations, fuelling genetic instability favouring carcinogenesis. Free dNTP are more easily damaged by ROS and are cleared from the nucleotide pool by dNTP pyrophosphatases and the nucleoside diphosphate linked moiety X family (Nudix) hydrolases, consisting of 22 members. These highly specialized proteins hydrolyse oxidized lesions such as 8-oxodGTP present in the nucleotide pool, thus preventing the incorporation of oxidized nucleotides into the RNA or the DNA. Cancer cells sustain abnormally high levels of ROS generated by deregulated metabolism and protein translation. Preliminary data from the host laboratory suggest that the Nudix hydrolase MTH1 is overexpressed in cancer and that cancer cells require its catalytic activity for survival. This is interesting, as normal cells do not rely on MTH1 for survival. Small molecule inhibitors from the host laboratory targeting MTH1, effectively kill transforming cells but not the parental immortalized cells. Thus, I hypothesize that the Nudix hydrolases may play important roles in cancer, and that insight into this pathway can be exploited to design novel anti-cancer strategies. The functions of a large portion of the 22 Nudix hydrolases are unknown. The objective of this project is to determine the biological and biochemical roles of all the Nudix hydrolases in cancer, including resistance and relapse, and thereby identify potential novel targets for cancer therapy and biomarkers. This will be achieved by using established technology at the host institute such as synthetic lethality screens, and by developing a novel 3D multiparametric assay
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 genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics nucleotides
- medical and health sciences basic medicine physiology homeostasis
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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-2012-IEF
See other projects for this call
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
171 77 STOCKHOLM
Sweden
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.