CGDM · Cancer Gene Discovery Using Somatic Gene Transfer in Mice
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2012-04-01 → 2016-03-31
- Финансиране от ЕС
- 100 000 €
- Участници
- 1
- Схема
- MC-CIG
Линиите свързват координатора с партньорите.
Накратко на български
Генетичните мутации, които задействат рака, се изследват чрез създаване на трансгенни чернодробни модели при мишки. Това помага да се разбере как конкретни вредни промени в клетките влияят на развитието на заболяването в живия организъм.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Cancer Gene Discovery Using Somatic Gene Transfer in Mice
After a long research period spent abroad, the PI started to build his independent research group in 2011; the Laboratory of Cancer Genome Research (http://www.szbk.u-szeged.hu/gen_cancer_genome_research.php) at the Institute of Genetics, Biological Research Centre (BRC), Szeged, Hungary. In the BRC he launched independent research on the examination of the genetic drivers of cancer development. The main research objective of the new laboratory, that was planned to be accomplished by the support of the MC-CIG grant, the creation of a somatic gene transfer system in the mouse liver, has substantially been achieved. The laboratory successfully created a highly efficient transgenic cell replacement system in mice, allowing to build transgenic liver models composed of >95% transgenic hepatocytes. To reach this goal the research group harnessed the mouse model of human tyrosinemia type I, a fatal disease with progressive liver dysfunction, and the transposon-based chromosomal delivery of the therapeutic gene for either ex vivo or in vivo genetic correction of the diseased primary hepatocytes. The successful correction of the diseased cells induced an intensive liver regeneration, finally resulting in a complete replacement of diseased cells with corrected ones. Importantly, this cell replacement system also allows the efficient co-introduction of any arbitrary transgene of interest together with the therapeutic gene, into the genome of the liver repopulating hepatocytes. Coupling of the therapeutic gene with transgenes modeling cancer driver mutations enables the PIs laboratory to test the in vivo effect of harmful somatic mutations potentially initiating cancer, a disease dependent on the accumulation of somatic genetic events. Due to the fact that the established somatic gene transfer system is utilizing transposon-based ex vivo or in vivo gene therapeutic protocols, the laboratory is also investigating and developing further such gene therapeutic protocols. By the help of the MC-CIG grant the PI could successfully establish his independent research group and demonstrate a good scientific progress to be awarded with a permanent position in the Institute of Genetics, BRC, Szeged, Hungary.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Cancer is the leading cause of death in the developed world. Significant emphasis has recently been placed on the characterization of the human cancer genome. However, the genetic complexity of cancer has complicated the identification of driver mutations among the more abundant passenger mutations found in tumours. Forward genetic screens are powerful methods to identify genes involved in specific biological processes like cancer formation. However the difficulties and costs currently associated to such screens in vivo in mammalian systems are equally enormous.Here I propose the creation of a novel site-directed gene transfer system, allowing efficient and controlled somatic gene transfer in vivo in mice. This approach offers the possibility for the rapid creation of large number of somatic clones, over-expressing target proteins, or carrying transgenes to trigger RNAi response against the targeted gene products.I plan to screen cancer related miR-based gene knockdown libraries in this system, for the identification of novel genes involved in suppressing tumour formation. Recent findings are emphasizing the role of genomic instability caused by errors of DNA repair in the development of cancer. Using candidate gene approach I would like to investigate such mechanisms by the help of the proposed in vivo test system.
Оригинален текст от CORDIS (на английски).
Участници
- HUN-REN SZEGEDI BIOLOGIAI KUTATOKOZPONT · SzegedКоординаторУнгария
Връзки
Данни: CORDIS, © Европейски съюз