ABSTRACT: EMG produced TPA metagenomics assembly of PRJNA703330 data set (Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis).
Project description:Mutations that introduce premature termination codons (PTCs) within protein-coding genes are associated with incurable and severe genetic diseases. Many PTC-associated disorders are life-threatening and have no approved medical treatment options. Suppressor transfer RNAs (sup-tRNAs) with the capacity to promote translational readthrough of PTCs represent a promising therapeutic strategy to treat these conditions; however, developing novel sup-tRNAs with high efficiency and specificity often requires extensive engineering and screening. Moreover, these efforts are not always successful at producing more efficient sup-tRNAs. Here we show that the pyrrolysine tRNA (tRNAPyl), which naturally translates the UAG stop codon, offers an attractive scaffold for developing potent sup-tRNAs that restore protein synthesis from PTC-containing genes. We created a series of rationally designed Pyrrolysine tRNA Scaffold Suppressor-tRNAs (PASS-tRNAs) that are substrates of bacterial and human alanyl-tRNA synthetase. Using a PTC-containing reporter gene, PASS-tRNAs restore protein synthesis to wild-type levels in bacterial cells. In human cells, PASS-tRNAs display robust and consistent translation activity in two distinct PTC reporter genes with high codon specificity and no observed cytotoxic effects. Collectively, these results unveil a new class of highly efficient sup-tRNAs with great potential for tRNA-based therapeutics.
2025-02-20 | PXD044322 | Pride
Project description:EMG produced TPA metagenomics assembly of the Hot Lake Unicyanobacterial Consortia (microbial mat metagenome) data set.
| PRJEB24113 | ENA
Project description:EMG produced TPA metagenomics assembly of PRJNA285502 data set (Fecal microbiota transplantation (FMT) for ulcerative colitis).
Project description:There is no noninvasive solution for tPA-resistant thrombi while endovascular thrombectomy is the last option. Here, we proposed neutrophil extracellular traps (NETs), ε-(γ-glutamyl)lysine isopeptide bonds and fibrin scaffold as keychain in tPA-resistant thrombus, which was confirmed in the thrombi retrieved from stroke patients. A theranostic platform was designed for the combination of sonodynamic and mechanical thrombolysis under the guidance of ultrasonic imaging. Three rounds of 10 min noninvasive treatment led to the breakdown of the keychain, achieving great recanalization rate of 90% in rat occlusion model while tPA only made 10% improvement. RNA sequencing results and endothelium functional tests jointly indicated that the vascular homeostasis can be effectively reconstructed. The noninvasive theranostic capability presented in pig’s lengthy thrombi (>8mm) and thrombosis-susceptible tissue engineered vascular grafts (TEVGs) indicated its clinical transformation prospects. Taken together, this non-invasive theranostic platform provides a new strategy for tPA-resistant thrombi.
Project description:Genetic variations were successfully associated among patients with coronary artery disease using Illumina Cardiometabochip containing 1,96,725 SNPs Illumina Cardio-metabochip is a custom designed SNP microarray containing 1,96,725 SNPs designed by several GWAS and consortia