Project description:The aim of this experiment was to determine if the development of resistance to antibiotics can be driven by the concentration and speciation of Cu. Experimental setup was designed to investigate two hypotheses for which two strains of Gram- bacteria have been selected: - Do TE enhance AR in resistant bacteria? Resistant strain: Bioluminescent Pseudomonas aeruginosa PAO1 (Xen41, Tetracycline resistant) - Do TE induce AR in sensitive bacteria? Sensitive strain: Pseudomonas aeruginosa PAO1 (Wild Type)
Project description:Medulloblastoma (MB), the most common malignant pediatric brain tumor, comprises of four molecularly and clinically distinct subgroups (termed WNT, SHH, Group3, and Group4). Prognosis varies based on genetic and pathological features associated with each molecular subgroup. WNT-MB, considered low-risk, are rarely metastatic and contain activating mutations in CTNNB1; Group3-MB, commonly classified as high-risk, are frequently metastatic and can contain genomic alterations resulting in elevated MYC expression. Here we compare model systems of low-risk WNT-MB to high-risk Group3-MB to identify tumor and microenvironment interactions that could contribute to features associated with poor outcome. Compared to Group3-MB, we find that WNT-MB display enrichment in gene sets related to extracellular matrix (ECM) regulation and cellular adhesion. Exogenous expression of MycT58A in murine WNT-MB models significantly accelerates growth and results in metastatic disease. In addition to down-regulation of ECM regulation and cell adhesion pathways, we also identified immune system interactions among the top down-regulated signaling pathways following MycT58A expression. Taken together, our data provides evidence that increased Myc signaling can promote the growth and metastasis of WNT-MB.
Project description:Group3 Medulloblastoma is a highly malignant pediatric brain tumor and despite patients harboring different genetic alterations they are treated with similar therapies. Here, we perform an in-vivo Patient-Specific screen and we identify Otx2 and c-Myc as strong inducers of Group3 Medulloblastoma. We demonstrate that the chromatin modifier Smarca4, also mutated in human patients, is able to reduce Otx2/c-Myc tumorigenic activity in-vivo. Furthermore, Otx2/c-Myc co-overexpression in human cerebellar organoids generates Medulloblastoma-like organoids that induce brain cancer in mice with a DNA methylation signature similar to human Group3 MB. Finally, inhibition of histone methyltransferases reduces Otx2/c-Myc tumorigenesis in ex-vivo culture and in human cerebellar organoids. Therefore, understanding the role of different altered genes in Medulloblastoma patients will be of great importance to develop new personalized therapies.