Objective
The macrodomain is a ubiquitous protein module known to bind to ADP-ribose derivatives, which diverged through evolution to support protein functions involved in DNA repair and the maintenance of genomic stability, transcriptional regulation, cell signaling, telomere dynamics, necrosis and apoptosis. Derivatives of ADP-ribose are synthesized by NAD+-dependent protein modification enzymes poly(ADP-ribose) polymerases (PARPs) and NAD+-dependent protein deacetylases (sirtuins). PARPs attracted enormous attention over the past several years, when it was demonstrated that permeable PARP inhibitors are highly effective against hereditary breast and ovarian cancers, as well as against acute cardiovascular conditions such as myocardial infarction and stroke. Given the apparent impact and prevalence of these diseases, there has been a rapidly growing interest in the search for alternative targets operating in PARP-dependent pathways that can be explored in therapy. However, these efforts have been hampered by our lack of knowledge about the mechanistic basis of cellular processes regulated by PARPs. In the first two sections of this proposal we will focus on the characterization of the two human macrodomain proteins poly(ADP-ribose) glycohydrolase (PARG) and the chromatin remodeler ALC1 (Amplified in Liver Cancer) that act as mediators of PARP-dependent signalling and have been implicated in human disease. Furthermore, in the third section we will study the sirtuin-linked macrodomain proteins found exclusively in fungal and bacterial pathogens and analyze their importance virulence. Collectively, the aims of this proposal are to define the molecular mechanisms governing the ADP-ribosylation-dependent signalling pathways mediated by several macrodomain proteins that are implicated in human disease. We feel that these studies can make a significant contribution to human health by providing the ground-work for the development of novel drugs that will ultimately provide cures.
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 oncology liver cancer
- natural sciences biological sciences cell biology cell signaling
- natural sciences biological sciences genetics DNA
- medical and health sciences basic medicine neurology stroke
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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.
ERC-2011-StG_20101109
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.
Host institution
OX1 2JD Oxford
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.