| title: | Synthetic nucleic acid binding molecules and cis-element analogs as regulators of transcription. |
|---|---|
| reg no: | ETF5137 |
| project type: | Estonian Science Foundation research grant |
| subject: |
1.8. Molecular Biology 3. Medical Sciences |
| status: | completed |
| institution: | Institute of Chemical Physics and Biophysics |
| head of project: | Andres Valkna |
| duration: | 01.01.2002 - 31.12.2005 |
| description: | Gene expression underlies important biological processes including development, immune defences, and tumorigenesis. Many cancers are now known to result from mutations that alter the way genes are switched on and off. A current goal in molecular medicine is the development of new strategies to interfere with gene expression in living cells in the hope that novel therapies for human disease will result from these efforts Cancer is the second most common cause of death in the developed world causing enormous human suffering and significant economic losses. It has been shown that environmental factors like UV radiation induces mutations in Sonic hedgehog factor receptor gene PTCH (human homolog of Drosophila patched receptor) that leads to the loss of function in this signalling pathway. Transcriptional effector for this signalling pathway is proto-oncogene GLI-1. The general objective of this interdisciplinary project is to develop and test the prototypes of a new generation of anti-cancer drugs that interfere with transcription either by blocking DNA or DNA binding molecules (transcription factors). The potential of these molecules to regulate transcription will be tested both in vitro and in vivo. Transcription factor GLI and respective cis-elements will be used as targets for previously mentioned molecules. We plan to use different approaches to regulate GLI related transcription: decoy oligonucleotides, antigene PNAs and polyamides. Cellular delivery by cell-penetrating peptides (transportan and its shorter analogs) will be used to target these drugs. The study will yield new information about the mechanism of protein/nucleic acid interaction and regulation of gene expression thereby helping to better understand this basic biological process. Molecules used in this study will have practical significance as substances to regulate gene expression and could give leads to possible anticancer drugs. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Monika Drews | NICBP | Senior Scientist | |
| 2. | Ants Kask | NICBP | Senior Scientist | |
| 3. | Anne Meikas | NICBPI/TTU | M.Sc. stud | |
| 4. | Piret Tiigimägi | NICBPI/TTU | Ph.D. stud | |
| 5. | Robert Tsanev | NICBPI/TTU | Ph.D. stud | |
| 6. | Andres Valkna | .National Institute of Chemical and Biophysics. | senior researcher | |