Project description:Amplification of a ~2.5 megabase region on chromosome 9p24 is frequent in both primary mediastinal B-cell lymphoma (PMBL) and Hodgkin's lymphoma (HL). To identify the oncogenic genes in this interval, we created a RNA interference library targeting amplicon genes. A genetic screen using this library identified three genes that are essential for the proliferation and survival of PMBL and HL lines with this amplicon, which encode the kinase JAK2, the histone demethylase JMJD2C and a gene of unknown function, RANBP6. Inhibition of JAK2 and JMJD2C cooperated in killing these lymphomas and in remodeling their chromatin by globally increasing trimethylation of lysine 9 on histone H3 (H3K9me3) and heterochromatin formation. JAK2 and JMJD2C inhibition silenced MYC and its target genes, which coincided with an increase in H3K9me3 and the heterochromatin protein HP1alpha at the MYC locus. We conclude that amplification of JAK2 and JMJD2C cooperatively reprograms the PMBL and HL epigenome, sustaining their survival and proliferation.
Project description:Proteomic strategy to define therapeutically relevant targets in cell lines that contain the 11q13 amplicon compared to those that do not and to ascertain which genes are amplified at the protein level and, concomitantly, are key drivers for tumor growth and/or maintenance. Furthermore, so called passenger genes that are amplified with driver genes and a manifest on the cell surface can be attractive targets for an antibody – drug conjugate approach (ADC).
Project description:Microplastics (MPs) as widespread contamination pose high risk for aquatic organisms.Intestinal microbiotahas have high interaction with immune system of host body. In this study, intestinal microbiota of zebrafish after Polystyrene (PS-MPs) exposure were characterized by 16S rDNA amplicon sequencing. We found that 100nm and 200μm PS-MPs exposure significantly increased diversity of intestinal microbiota and all the three sizes of PS-MPs increased abundance of pathogenic bacteria.
Project description:Amplification of a ~2.5 megabase region on chromosome 9p24 is frequent in both primary mediastinal B-cell lymphoma (PMBL) and Hodgkin's lymphoma (HL). To identify the oncogenic genes in this interval, we created a RNA interference library targeting amplicon genes. A genetic screen using this library identified three genes that are essential for the proliferation and survival of PMBL and HL lines with this amplicon, which encode the kinase JAK2, the histone demethylase JMJD2C and a gene of unknown function, RANBP6. Inhibition of JAK2 and JMJD2C cooperated in killing these lymphomas and in remodeling their chromatin by globally increasing trimethylation of lysine 9 on histone H3 (H3K9me3) and heterochromatin formation. JAK2 and JMJD2C inhibition silenced MYC and its target genes, which coincided with an increase in H3K9me3 and the heterochromatin protein HP1alpha at the MYC locus. We conclude that amplification of JAK2 and JMJD2C cooperatively reprograms the PMBL and HL epigenome, sustaining their survival and proliferation. Signal from untreated shRNA cells or DMSO control cells (Cy3) was compared to 4 dox-treated JAK2 shRNA cells, 4 dox-treated JMJD2C shRNA cells, or 8 JAK2 inhibitor-treated cells (Cy5).
Project description:Contaminated aquifer (Dusseldorf-Flinger, Germany) templates extracted from 5 sediment depths ranging between 6.4 and 8.4 m below ground and over 3 years of sampling were amplified for amplicon pyrosequencing using the primers Ba27f (5’-aga gtt tga tcm tgg ctc ag-3’) and Ba519r (5’- tat tac cgc ggc kgc tg-3’), extended as amplicon fusion primers with respective primer A or B adapters, key sequence and multiplex identifiers (MID) as recommended by 454/Roche. Amplicons were purified and pooled as specified by the manufacturer. Emulsion PCR (emPCR), purification of DNA-enriched beads and sequencing run were performed following protocols and using a 2nd generation pyrosequencer (454 GS FLX Titanium, Roche) as recommended by the developer. Quality filtering of the pyrosequencing reads was performed using the automatic amplicon pipeline of the GS Run Processor (Roche), with a slight modification concerning the valley filter (vfScanAllFlows false instead of TiOnly) to extract the sequences. Demultiplexed raw reads were furhter trimmed for quality and lenght (>250 bp).