Molecular Oncology Early Research Training

Final Activity Report Summary - ONCO-TRAIN (Molecular Oncology Early Research Training)

The ONCO-TRAIN is a Marie Curie Early stage research training (EST)-funded programme, whose fundamental objective was to offer graduate students a structured and comprehensive training in basic and applied cancer research.

Current cancer research is a multidisciplinary research field, including disciplines such as biology, medicine, computer sciences, physics and chemistry, which creates the unprecedented demand for scientists with ample cross-disciplinary training in the numerous involved sectors. In order to address this urgent demand, the ONCO-TRAIN programme sought to offer highly multidisciplinary training in oncology. Apart from their own choice of working on a specific field, fellows had the possibility of accessing first line technologies and different, complementary and interdisciplinary research approaches such as molecular pathology, animal models, molecular oncology, structural biology, experimental therapeutics and bioinformatics. All fellows collaborated successfully and contributed significantly through their projects to the ongoing research of the different groups of the 'Centro Nacional Investigaciones Oncologicas' (CNIO). Eight three-year fellowships were offered to perform PhD studies.

A list with the different research activities carried out by ONCO-TRAIN participants and their principal results is subsequently presented:
1. In terms of structural biology of metastatic cascade protein components, the project covered protein expression and purification, as well as crystallisation techniques. Some of the genes that were successfully purified during the project were calbindin2, transgelin, Raf kinase inhibitor protein (RKIP), Differentiation-related gene one (DRG1) and several proteins of the complex SET. Crystals of a yeast ortholog of DRG1, namely Rbg1, in complex with TMA46 and several complexes involving RKIP were also obtained.
2. Regarding the development of technological platforms for the identification of novel modulators of forkhead box O (FOXO) activity, the project focussed on the PI3K-Akt pathway, one of the most frequently altered pathways in human cancers. The project developed and validated distinct cell-based assays that were suitable for that purpose.
3. As far as the analysis of the molecular mechanisms that regulated the G2/M-phase transition of the cell cycle was concerned, the project uncovered a novel mechanism by which p38 mediated signals could be converted into chromatin structural changes, thereby facilitating transcriptional activation during cell differentiation.
4. In terms of the application of large scale molecular technologies in tumour analysis, this project focussed on the analysis of transversal alterations in tumorigenesis, such as activation or somatic mutation of the transcription factor NF-kB, which could signal therapeutic targets for intervention.
5. Regarding the gene expression analysis using complementary Deoxyribonucleic acid (cDNA) microarrays in hereditary breast tumours, the project focussed on hereditary breast cancer research, such as analysis of large rearrangements of the Breast cancer one (BRCA1) and Breast cancer two (BRCA2) genes. The study revealed the molecular complexity of BRCA1 breast tumours, which were found to display similarities to sporadic tumours, and suggested possible prognostic implications.
6. Moreover, research was carried out in the molecular cytogenetic group and consisted of the elaboration of a differential diagnostic of low grade lymphoma by using the technique of comparative genomic hybridisation (CGH) arrays. As a consequence of this work the fellow published, as first author, two major papers in peer reviewed journals, namely Haematologica and Oncogene.
7. In terms of chemical genetics and inducible knock in models, new approaches to study polo kinases and their evaluation as cancer targets were investigated. The project generated Plk1-deficient mice and the fellow was involved in the characterisation of the essential roles of Plk1 in vivo. This research led to the discovery of new roles of this kinase in the nervous and cardiovascular systems that might have relevant implications in human disease.
8. Finally, regarding the analysis of telomere length of cells in a tissue section, the project contributed greatly to the development of telomapping, a method for the generation of topological maps of telomere length in which confocal telomere Quantitative fluorescent in situ hybridisation (Q-FISH) was performed directly in tissue sections coupled to a single cell high-throughput metamorph image analysis platform.

Final Activity Report Summary - ONCO-TRAIN (Molecular Oncology Early Research Training)

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