Objective
The aim of the proposal is the establishment of a yeast-three hybrid system for the identification of mycobacterial proteins that bind to selected small molecules. It is envisioned to use the system to (i) find targets of active molecules that have been identified in whole cell screenings; (ii) identify mycobacterial proteins that activate or deactivate drugs; (iii) establish simple assays for proteins previously identified as key targets. Since the identification of protein targets of a small molecule drug is challenging, improved methods are asked that facilitate their discovery. With the recent development of an optimised yeast three-hybrid system in the Johnsson group, the stage is set for its application to identify small molecule-protein interactions. This adapted version of the classical yeast two-hybrid system features an additional third synthetic hybrid ligand. It uses SNAP-tag (a self-labelling protein tag) as an anchor protein and O6-benzylguanine (BG) derivatives as synthetic ligands. Currently it allows the screening of human cDNA libraries for small molecule-protein interactions in yeast. To apply this system for drug discovery against tuberculosis, the construction of genomic libraries of M. smegmatis was initiated and libraries of M. tuberculosis will follow. We would start with conjugating known TB drugs (with known or unknown targets) to BG and screen them against genomic libraries. Suggested drugs to start are rifampicin and BTZ as positive controls and clofazimine and thiocarlide as drugs with unclear mechanism of action. Noteworthy that the three-hybrid screen can also be applied for the identification of proteins that activate a certain drug. Furthermore, once a protein-ligand is identified, the hybrid assay can be used to screen for new drugs against this target in HTS compatible competition 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.
- medical and health sciences basic medicine pharmacology and pharmacy drug discovery
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine pneumology tuberculosis
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.
FP7-PEOPLE-2009-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
1015 LAUSANNE
Switzerland
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.