Project description:Programmable RNA-targeting tools provide the unique opportunity to study RNA regulation and control gene expression in an endogenous environment. However, the temporal control over these systems is lacking, rendering studies on the temporal control of regulation challenging. Here, we report the development of a small molecule-controllable RNA effector system to overcome this challenge.
Project description:We develop a small molecule-inducible dimerization strategy of RBP of interest and adenosine deaminase domain to profile dynamic RBP-RNA interactions.
Project description:We systematically screened novel culture systems designed for naïve human embryonic stem cells via high-content screening and small molecule combinations. Our findings indicate that the cell lines established through this innovative system closely mimic the in vivo Inner Cell Mass (ICM) concerning both transcriptome profiles and methylation patterns. Additionally, we observed an elevated level of methylation specifically on transposable elements within these cell lines. Furthermore, our investigations suggest that the genomic stability of this novel system may exhibit superior qualities.
Project description:Crimean-Congo hemorrhagic fever (CCHF) caused by CCHF virus (CCHFV) is one of the epidemic-prone diseases prioritized by the World Health Organisation as public health emergency with an urgent need for accelerated research. The trajectory of host response against CCHFV is multifarious and remains unknown. Here, we reported the temporal spectrum of pathogenesis following the CCHFV infection using genome-wide blood transcriptomics analysis followed by advanced systems biology analysis, temporal immune-pathogenic alterations, and context-specific progressive and postinfection genome-scale metabolic models (GSMM) on samples collected during the acute (T0), early convalescent (T1), and convalescent-phase (T2). The interplay between the retinoic acid-inducible gene-I-like/nucleotide-binding oligomerization domain-like receptor and tumor necrosis factor signaling governed the trajectory of antiviral immune responses. The rearrangement of intracellular metabolic fluxes toward the amino acid metabolism and metabolic shift toward oxidative phosphorylation and fatty acid oxidation during acute CCHFV infection determine the pathogenicity. The upregulation of the tricarboxylic acid cycle during CCHFV infection, compared to the noninfected healthy control and between the severity groups, indicated an increased energy demand and cellular stress. The upregulation of glycolysis and pyruvate metabolism potentiated energy generation through alternative pathways associated with the severity of the infection. The downregulation of metabolic processes at the convalescent phase identified by blood cell transcriptomics and single-cell type proteomics of five immune cells (CD4+ and CD8+ T cells, CD14+ monocytes, B cells, and NK cells) potentially leads to metabolic rewiring through the recovery due to hyperactivity during the acute phase leading to post-viral fatigue syndrome.
Project description:We systematically screened novel culture systems designed for naïve human embryonic stem cells via high-content screening and small molecule combinations. Our findings indicate that the cell lines established through this innovative system closely mimic the in vivo Inner Cell Mass (ICM) concerning both transcriptome profiles and methylation patterns. Additionally, we observed an elevated level of methylation specifically on transposable elements within these cell lines. Furthermore, our investigations suggest that the genomic stability of this novel system may exhibit superior qualities.