Targeting of the cell cycle regulated e2fs-pocket protein pathways using peptide aptamers - a new tool for cancer therapy
FP4 — Training and Mobility of Researchers
- Duration
- 1998-03-01 → 2000-02-29
- EU contribution
- —
- Participants
- 2
- Scheme
- RGI
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Project objective
Research objectives and content The E2F family of transcription factors play a crucial role in regulating cell proliferation integrating and co-ordinating cellcycle events and transcriptional activity. There is enough evidence to demonstrate the importance of these transcription factors in the abnormal function of the cell-cycle. First, it has been already established a link between the loss of function of the pRB protein, which is a regulator of the E2Fs factors, and a variety of human tumours. Second it has been observed in a number of human tumours mutations on genes regulating the pocket proteins (RB). And third, overexpression of E2F was shown to cause neoplasic transformation of cells in culture and growth in soft agars. Thus, the objective of this project is to develop innovative tools to target in vivo specifically each E2F subtype for both, better knowledge of the function of each subtype and to find new drugs targeted to E2Fs as antiproliferative agents. In a first stage, peptide Aptamers that interact specifically with each member of the E2Fs and the pocket proteins will be selected and tested in vitro. In a second stage the selected Aptamers will be replaced by unconstrained synthetic peptides and again tested in vitro. Finally, the selected peptides and Aptamers will be studied in vivo by microinjection in human cells in culture and in cell-lines expressing conditional alleles coding for active Aptamers. Those molecules which block cell growth will be further tested as antiproliferative agents on transformed human cell-lines. Training content (objective, benefit and expected impact) The expansion of the project will give me the possibility to develop innovative tools to target specifically a protein (E2F) which function is directly related to the control of the cell-cycle. This new technology will facilitate both, a better understanding of its function and a new approach for the cancer therapy. From a professional point of view this is a crucial step in my career going towards industry. The present project will have a big impact not only in the scientific community where it will resolve the fundamental question about the specific role of each E2F subtype in the cell-cycle regulation, but also in the industrial context where it represents a powerful novel tool to select inhibitors of key elements of the cell proliferation machinery opening the door to new therapies. Links with industry / industrial relevance (22) The project will be done in tight collaboration with the Biotech company SYNT:EM (Montpellier) interested in the development of new antiproliferative drugs. The part of the project concerning the synthesis of peptides and the modelling of molecules will be done by the applicant at the mentioned company.
Original text from CORDIS.
Participants
Links
Data: CORDIS, © European Union