Project description:Primary objectives: The primary objective is to investigate circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Primary endpoints: circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Project description:Investigation of whole genome gene expression level changes in a Brucella melitensis delta prlr mutant compared to the wild type strain. The mutants analyzed in this study are further described in A. Mirabella, R-M Yanez, R.M. Delrue, S. Uzureau, M.S. Zygmunt, A. Cloeckaert, X. De Bolle, J.J. Letesson (2012). The two component system PrlS/PrlR of Brucella melitensis is required for persistence in mice and appears to respond to ionic strength. Microbiology
Project description:Investigation of whole genome gene expression level changes in a Brucella melitensis delta prlr mutant compared to the wild type strain. The mutants analyzed in this study are further described in A. Mirabella, R-M Yanez, R.M. Delrue, S. Uzureau, M.S. Zygmunt, A. Cloeckaert, X. De Bolle, J.J. Letesson (2012). The two component system PrlS/PrlR of Brucella melitensis is required for persistence in mice and appears to respond to ionic strength. Microbiology A six chip study using total RNA recovered from three separate wild-type cultures of Brucella melitensis 16M and three separate cultures of a prlR mutant strain. Each chip measures the expression level of 3,198 genes from Brucella melitensis 16M with nineteen 60 mer probe pairs (PM/MM) per gene, with three-fold technical redundancy.
Project description:Outer membrane vehicles (OMVs) are secreted from gram-negative bacterium to enable bacterial survival and regulate microbial interactions within bacterial communities. The components of OMVs comprise RNA, but the generation as well as the function of OMVs RNA needs to be elucidated. Here, we report that a small non-coding RNA fragment tRF-Leu-CAG, detected in Brucella OMVs, regulates interleukin 13 receptor subunit alpha 1 (IL13RA1) to activate the phosphorylation of Signal Transducer and activator of Transcription 6 (STAT6) via the JAK-STAT6 pathway to reprogram macrophage M2 polarization. We identified the presence of tRF-Leu-CAG in Brucella OMVs by sRNA sequencing and tRF sequencing from bacterial lysate. tRF-Leu-CAG interacts with argonaute 2 (AGO2) protein to exert its function. Meanwhile, the interleukin 13 receptor subunit alpha 1 (IL13RA1) was proved to be the target genes of tRF-Leu-CAG. Overexpression of phosphorylated STAT6 by western blot further substantiated that tRF-Leu-CAG promotes macrophage M2 polarization via the JAK-STAT6 pathway. Finally, tRF-Leu-CAG and small interfering IL13RA1 facilitates the survival of Brucella in macrophage. Thus, our results highlight the function of tRF-Leu-CAG in Brucella OMVs by reprogramming macrophage M2 polarization to improve the survival of extracellular Brucella. The study unravels a new mechanism of intracellular parasitism and immune escape in Brucella, providing strategy for the mechanisms of other intracellular parasitic bacteria.
2025-01-27 | GSE287747 | GEO
Project description:Brucella whole genome sequencing in Israel
Project description:To explore the role of Brucella BI-1 in Brucella suis S2, we constructed the Brucella BI-1 deletion mutant strain and its complementary strain. We then determined the effect of Brucella BI-1 deletion on the physiological characteristics of Brucella suis S2 and revealed them via integrated transcriptomic and proteomic analyses. Brucella BI-1 deletion altered the membrane properties of Brucella suis S2 and decreased its resistance to acidic pH, H2O2, polymyxin B, and lincomycin. Additionally, deleting Brucella BI-1 led to defective growth, cell division, and viability in Brucella suis S2. In conclusion, our results revealed that Brucella BI-1 is a bacterial cytoprotective protein involved in membrane homeostasis, cell division, and stress resistance in Brucella suis S2.