Characterisation of concurrent liver injury and oncogenes in a plasmid-based mouse model of liver cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA728101 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14466500.fastq.gz | Fastqsanger.gz | |||
| SRR14466501.fastq.gz | Fastqsanger.gz | |||
| SRR14466502.fastq.gz | Fastqsanger.gz | |||
| SRR14466503.fastq.gz | Fastqsanger.gz | |||
| SRR14466504.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:This experiment aimed to characterise transcriptomes of plasmid-based mouse models of liver cancer, hepatotoxin-induced chronic liver injury and the combination thereof. In detail, C57BL/6JAusb mice received hydrodynamic tail vein injection (HTVI) of plasmids encoding Sleeping Beauty transposase (SB), alone or in combination with transposon plasmids encoding myristylated AKT1 (AKT), c-Met and NRasV12 (NRas), previously characterised by Ho et al. (2012) (Hepatology 55(3):833-45) and Hu et al. (2016) (Sci Rep 6:20484). 8-10 days post-HTVI, mice began biweekly intraperitoneal (i.p.) injections of saline or the hepatotoxin thioacetamide (TAA), 10-11 doses.
2023-05-31 | GSE174074 | GEO
Project description:Low copy number plasmids must encode maintenance mechanisms, such as partitioning systems, to ensure that the plasmid is sustained through host generations. Plasmid partition systems segregate sister plasmid copies and are subdivided into different types based on the NTPase they encode. The characterisation and distribution of partition system types is well understood in Enterobacteriaceae plasmids. However, how these systems maintain plasmids and are distributed across wider bacterial diversity is poorly understood. We used the Streptomyces coelicolor A3(2) plasmid SCP1, which encodes two type Ia partition systems, as a model to investigate this. Sequence analysis of the SCP1 partition systems revealed that both ParB proteins contain less conserved CTP-binding pockets, suggesting one or both proteins may not behave like canonical ParB proteins. However, using a combination of chromatin immunoprecipitation with deep sequencing (ChIP-seq) we demonstrate that both the SCP1 ParB proteins, ParB1 and ParB2, bound to distinct parS sites on SCP1, and accumulate, or spread, on DNA approximately 20 kb away from their initial parS loading site. Together, our findings further our understanding of Streptomyces plasmid maintenance by providing the first functional characterisation of two type Ia partition systems coexisting on a single plasmid and offer new insights into the diversity and distribution of plasmid partition systems.
2025-12-01 | GSE311144 | GEO
Project description:Low copy number plasmids must encode maintenance mechanisms, such as partitioning systems, to ensure that the plasmid is sustained through host generations. Plasmid partition systems segregate sister plasmid copies and are subdivided into different types based on the NTPase they encode. The characterisation and distribution of partition system types is well understood in Enterobacteriaceae plasmids. However, how these systems maintain plasmids and are distributed across wider bacterial diversity is poorly understood. We searched a large and diverse plasmid database to identify the distribution of partition system types and found that plasmids encoding multiple partition systems are more widespread than previously realised, composing ~19% of all plasmids predicted to encode partition systems. Many of these plasmids were predicted to encode multiple partition systems of the same type, which had never been studied previously. We used the Streptomyces coelicolor A3(2) plasmid SCP1, which encodes two type Ia partition systems, as a model to investigate this. Sequence analysis of the SCP1 partition systems revealed that both ParB proteins contain less conserved CTP-binding pockets, suggesting one or both proteins may not behave like canonical ParB proteins. However, using a combination of chromatin immunoprecipitation with deep sequencing (ChIP-seq), biochemistry and mutagenesis we show that both ParB proteins behave like bone fide ParB proteins: they bound to distinct parS sites on SCP1, both proteins bound and hydrolysed CTP and both proteins required CTP and their cognate parS site to accumulate, or spread, on DNA. Intriguingly, however, only ParB1 was critical for SCP1 stability. Together, our findings further our understanding of Streptomyces plasmid maintenance by providing the first functional characterisation of two type Ia partition systems coexisting on a single plasmid and offer new insights into the diversity and distribution of plasmid partition systems.
2025-12-01 | GSE311147 | GEO
Project description:Single domain antibodies or antibody mimetics, such as monobodies, can be engineered to degrade undruggable targets via fusion to ubiquitin E3 ligases. In this study we developed multi-targeting biodegrader intrabodies by harnessing an inhibitor of apoptosis (IAP) E3 ligase RING domain, or the IAP-binding motif from SMAC/DIABLO. When fused with monobodies targeting the necroptotic death effector MLKL, IAP-binding intrabodies simultaneously targeted MLKL and IAPs for proteasomal degradation, thereby blocking necroptosis while sensitising cells to apoptosis. The potent degradative capacity of the IAP RING was demonstrated via its fusion to distinct antibody mimetics, with those targeting RAS enabling IAP and RAS proto-oncogenes to be concurrently eliminated. Quantitative proteomics identified that the anti-cancer potential of select IAP-binding intrabodies was due to their removal of the chromatin remodelling BAF complex. Consequently, we show that cancer cells exhibited IAP and BAF co-dependencies, with IAP RING intrabodies prolonging animal survival in an orthotopic breast cancer model. This work positions IAP-binding intrabodies as a novel class of biodegraders, with their multi-targeting capacity enabling the toggling of cell death modalities and eradication of cancer-drivers.
2026-03-03 | PXD061128 | Pride
Project description:Plasmid characterization in bacterial isolates in a tertiary healthcare facility in Kilimanjaro, Tanzania
| PRJEB53343 | ENA
Project description:Prospective study of accuracy of colonic polyp characterisation in vivo using high resolution white light endoscopy, narrow band imaging and chromoendoscopy.
| 2071358 | ecrin-mdr-crc
Project description:Different fusion oncogenes in acute myeloid leukemia (AML) have distinct clinical and laboratory features suggesting different modes of malignant transformation. Here we compare the in vitro effects of representatives of major groups of AML fusion oncogenes on primary human CD34+ cells. For the 3 d and 8 d time points, the oncogenes were retrovirally expressed in primary human CD34+ cells, with cells transduced with empty retroviral vector as controls. As retroviral transduction requires days, for the 6 h time point the oncogenes were expressed from a pTracer-CMV/Bsd plasmid using nucleofection. Cells nucleofected with empty pTracer-CMV/Bsd vector were used as a control.
2014-05-01 | E-GEOD-57194 | biostudies-arrayexpress
Project description:<p>Gut environments harbour dense microbial ecosystems in which plasmids are widely distributed. Plasmids facilitate the exchange of genetic material among microorganisms while enabling the transfer of a diverse array of accessory functions. However, their precise impact on microbial community composition and function remains largely unexplored. Here we identify a prevalent bacterial toxin and a plasmid-encoded resistance mechanism that mediates the interaction between Lactobacilli and Enterococci. This plasmid is widespread across ecosystems, including the rumen and human gut microbiota. Biochemical characterization of the plasmid revealed a defence mechanism against reuterin, a toxin produced by various gut microbes, such as Limosilactobacillus reuteri. Using a targeted metabolomic approach, we find reuterin to be prevalent across rumen ecosystems with impacts on microbial community structure. Enterococcus strains carrying the protective plasmid were isolated and their interactions with L. reuteri, the toxin producer, were studied in vitro. Interestingly, we found that by conferring resistance against reuterin, the plasmid mediates metabolic exchange between the defending and the attacking microbial species, resulting in a beneficial relationship or mutualism. Hence, we reveal here an ecological role for a plasmid-coded defence system in mediating a beneficial interaction. </p>
2023-08-10 | MTBLS7248 | MetaboLights
Project description:Characterisation of human CD4+ cells to gain more insights into regulatory processes.
2023-03-30 | GSE220530 | GEO