The evaluation of the profile of the kinomic and miRNomic for the exploration of new targets for molecular therapies are combinatorial in glioblastoma, omic approaches
The project proposed by the purpose the objectives set out within the Objective 1 of the proposal for a Program, the Kernel,the The identification and/or validation of the targets of the molecular pathology of the tumor, and degenerative disease and it will be carried out in the framework of the Laboratory of Biochemistry-Proteomics of PATHOLOGY, Victor Babes university.
The project is purpose the evaluation of the profile of the kinomic and miRNomic, in order to exploit new targets for molecular therapies for combinatorial – inhibitors of kinases: from the synthesis of natural bioactive. This study will be achieved through the assessment of the impact of the modulation of the nodes of the signal on the target protein, and the reglatorilor epigenetici -miRNA in glioblastoma (GBM).
Some of the most important waterfalls of the signaling dysregulated in GBM are the PI3K/Akt/mTOR and MAPK; their activation leads to the development of drug resistance. Because the function of the control posttranscripțională miRNAs play a central role in the process of signaling.
The project aims to a system approach that includes the evaluation of the networks of the signal on the new concept of the relationship between the molecules and the key of the signal, and myrrh. The study of disorder near you in relation to signaling in glioblastoma might be able to give you a new perspective on the innovative therapies combinatorial, conventional, and on the basis of natural bioactive compounds.
The elements of novelty and originality they are readily available for the generation of a panel of signaling molecules that have been selected by the modulation of the nodes in the key of a network of signaling through the blockers out of the synthesis or natural bioactive compounds. The data will generate a map of the signal comparison between the activity of the basal lamina, and the modified experimentally induced. This systematic approach is a novelty in the field of the science of my life: the correlation between the signaling proteins, and miRNA selected, the profile of the kinomic and miRNomic, providing the framework for a future confirmation/validation of potential targets in the therapy combinatorial targeted or customized.
First objective
The development of conceptual models for the approach to proteomics, transcriptomice, and epigenetic. The design and development of methods and models, to the experimental. The selection and development of cell cultures of primary derived from the tumor tissue and cell lines should be standardized.
Second objective
The evaluation of the profile of the kinomic the result of the modulation of intracellular signaling:
analysis of a panel of receptors of the area are involved in the pathogenesis of glioblastomului by the approach in proteomic multiplex.
– the analysis of the nodes of the signaling proteins, total and phosphorylated;
– the modulation of signaling through the inhibition of the PI3K and MAPK.
Third objective
The evaluation of the profile of the miRNomic the result of the modulation of intracellular signaling:
– the identification of the miRNA of the regulatory mechanisms and epigenetic (screening, high-throughput screen for mirnas);
– the assessment of changes in the epigenetic level, genomic DNA;
analysis of the degree of methylation, the global/proteins that are involved.
Fourth objective
Of natural bioactive modulators epigenetici, and signage.
Fifth objective
The purposes of validation, the establishment of linkages and the development of the potential of the algorithm for the therapy, combination, in glioblastomas.
Secondary objectives
- Implementation of the profile of kinomic/profile miRNomic as a systemic approach in the evaluation of the signature of the molecular glioblastomului;
- The configuration of the combination treatment inhibitors of kinases of the synthesis of the plus natural bioactive compounds;
- The dissemination of results through publications and presentations;
- The training of phd students and postdoctoral researchers involved in the project.
- The establishment of co-operation with other research institutions and clinical profile of the interested in the development and application of such innovative concepts;
- The development/establishment of international cooperation in the field of the project for the development of joint research projects
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