Dual functionality of the TasA amyloid protein in Bacillus physiology and fitness on the phylloplane
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PROVIDER: PRJNA511580 | ENA |
REPOSITORIES: ENA
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Project description:We report the application of a high-throughput technique, RNA-seq, to study the transcriptomic response of a Bacillus subtilis mutant for the tasA gene growing in biofilm-inducing solid medium (MSgg).
2020-03-22 | GSE124307 | GEO
Project description:Bacteria can form biofilms that consist of multicellular communities embedded in an extracellular matrix (ECM). In Bacillus subtilis, the main protein component of the ECM is the functional amyloid TasA. Here, we study further the roles played by TasA in B. subtilis physiology and biofilm formation on plant leaves and in vitro. We show that ΔtasA cells exhibit a range of cytological symptoms indicative of excessive cellular stress leading to increased cell death. TasA associates to the detergent-resistant fraction of the cell membrane, and the distribution of the flotillin-like protein FloT is altered in ΔtasA cells. We propose that, in addition to a structural function during ECM assembly and interactions with plants, TasA contributes to the stabilization of membrane dynamics as cells enter stationary phase.
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Project description:Tissue-resident memory CD8+ T cells (Trm) share characteristics and core residency gene programs with tumor-infiltrating lymphocytes (TILs). However, the transcriptional, metabolic and epigenetic regulation of Trm cell and TIL differentiation, maintenance and function are largely undefined. Furthermore, it is unknown whether metabolic and epigenetic manipulations can be employed to promote Trm/TIL functional programs for cancer immunotherapy. Here we report a critical mechanism programming the mitochondrial and epigenetic regulation of Trm/TIL functionality in situ. We found that mouse and human Trm/TIL expressed the transcription factor BHLHE40 and the BHLHE40-associated gene signature. Bhlhe40 was specifically required for Trm and TIL development and polyfunctionality. Local PD-1 signaling inhibited TIL Bhlhe40 expression, and Bhlhe40 was critical for TILs reinvigoration following anti-PD therapy. Mechanistically, Bhlhe40 sustained Trm/TIL mitochondrial fitness for the promotion of a functional epigenetic state. Building on these findings, we also identified an epigenetic and metabolic regimen that promoted Trm/TIL gene signatures associated with tissue residency and poly-functionality through in vitro T cell screening. Strikingly, this regimen empowered the anti-tumor activity of CD8+ T cells and possessed therapeutic potential even at an advanced tumor stage in mouse models. Our results provide mechanistic insights on the local regulation of Trm and TIL function, and offer a viable strategy for developing novel immunotherapeutic means for cancer.
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Project description:The transcription factor Bhlhe40 programs mitochondrial regulation of resident CD8+ T cell fitness and functionality
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Project description:T lymphocytes are essential contributors to the adaptive immune system and consist of multiple lineages that serve various effector and regulatory roles. As such, precise control of gene expression is essential to the proper development and function of these cells. Previously, we identified Snai2 and Snai3 as being essential regulators of immune tolerance partly due to the impaired function of CD4+ regulatory T cells in Snai2/3 conditional double knockout mice. Here we extend those previous findings using a bone marrow transplantation model to provide an environmentally unbiased view of the molecular changes imparted onto various T lymphocyte populations once Snai2 and Snai3 are deleted. The data presented here demonstrate that Snai2 and Snai3 transcriptionally regulate the cellular fitness and functionality of not only CD4+ regulatory T cells but effector CD8α+ and CD4+ conventional T cells as well. This is achieved through the modulation of gene sets unique to each cell type and includes transcriptional targets relevant to the survival and function of each T cell lineage. As such, Snai2 and Snai3 are essential regulators of T cell immunobiology.
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Project description:Complement protein C1q is induced after injury in the brain and during Alzheimer's disease and has been shown to protect against amyloid-beta induced neuronal death. In this study, we used microarray approach to identify the pathways modulated by C1q that are associated with neuroprotection. Immature rat cortical primary neurons are treated with fibrillar amyloid-beta peptides and/or C1q for 3h before RNA extraction and hybridization on rat Affymetrix microarrays. Supplementary file: Processed/normalized, probe-level signal intensities from neurons treated with amyloid-beta or C1q. Median signal intensity used as global normalization method, done with JMP genomics (v5.0) software.
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