Biology subjects

Schiller, M.

Publications and source records attributed to Schiller, M..

4 recordsLinked to original sources

bioRxiv2020

Remembering immunity: Neuronal ensembles in the insular cortex encode and retrieve specific immune responses

Increasing evidence indicates that the brain regulates peripheral immunity. Yet, it remains unclear whether and how the brain represents the state of the immune system. Here, we show that immune-related information is stored in the brains insular cortex (InsCtx). Using activity-dependent cell labeling in mice (FosTRAP), we captured neuronal ensembles in the InsCtx that were active under two different inflammatory conditions (DSS-induced colitis and Zymosan-induced peritonitis). Chemogenetic reactivation of these neuronal ensembles was sufficient to broadly retrieve the inflammatory state under which these neurons were captured. Thus, we show that the brain can encode and initiate specific immune responses, extending the classical concept of immunological memory to neuronal representations of immunity.

neuroscience↗

bioRxiv2019

Mapping and DNA sequence characterisation of the Rysto locus conferring extreme virus resistance to potato cultivar ‘White Lady’

Virus resistance genes carried by wild plant species are valuable resources for plant breeding. The Rysto gene, conferring a broad spectrum of durable resistance, originated from Solanum stoloniferum and was introgressed into several commercial potato cultivars, including White Lady, by classical breeding. Rysto was mapped to chromosome XII in potato, and markers used for marker-assisted selection in breeding programmes were identified. Nevertheless, there was no information on the identity of the Rysto gene. To begin to reveal the identification of Rysto, fine-scale genetic mapping was performed which, in combination with chromosome walking, narrowed down the locus of the gene to approximately 1 Mb. DNA sequence analysis of the locus identified six full-length NBS-LRR-type (short NLR-type) putative resistance genes. Two of them, designated TMV2 and TMV3, were similar to a TMV resistance gene isolated from tobacco and to Y-1, which co-segregates with Ryadg, the extreme virus resistance gene originated from Solanum andigena and localised to chromosome XI. Furthermore, TMV2 of White Lady was found to be 95% identical at the genomic sequence level with the recently isolated Rysto gene of the potato cultivar Alicja. In addition to the markers identified earlier, this work generated five tightly linked new markers which can serve potato breeding efforts for extreme virus resistance.

plant biology↗

bioRxiv2019

ChIPSummitDB: A ChIP-seq-based database of human transcription factor binding sites and the topological arrangements of the proteins bound to them

ChIP-Seq reveals genomic regions where proteins, e.g. transcription factors (TFs) interact with DNA. A substantial fraction of these regions, however, do not contain the cognate binding site for the TF of interest. This phenomenon might be explained by protein-protein interactions and co-precipitation of interacting gene regulatory elements. We uniformly processed 3,727 human ChIP-Seq data sets and determined the cistrome of 292 TFs, as well as the distances between the TF binding motif centers and the ChIP-Seq peak summits. ChIPSummitDB enables the analysis of ChIP-Seq data using multiple approaches. The 292 cistromes and corresponding ChIP-Seq peak sets can be browsed in GenomeView. Overlapping SNPs can be inspected in dbSNPView. Most importantly, the MotifView and PairShiftView pages show the average distance between motif centers and overlapping ChIP-Seq peak summits and distance distributions thereof, respectively. In addition to providing a comprehensive human TF binding site collection, the ChIPSummitDB database and web interface allows for the examination of the topological arrangement of TF complexes genome-wide. ChIPSummitDB is freely accessible at http://summit.med.unideb.hu/summitdb/. The database will be regularly updated and extended with the newly available human and mouse ChIP-Seq data sets.

bioinformatics↗

bioRxiv2019

Viral infection overcomes ineffectiveness of anti-tumoral CD8+ T cell mediated cytotoxicity

With the integration of PD-1 and CTLA-4 targeting immune checkpoint blockade into cancer treatment regimes, the anti-tumoral cytotoxicity of tumor-specific CD8+ T cells is well established. However, while the unresponsiveness of CD8+ T cells against big tumors is mainly explained by T cell exhaustion, other factors contributing to CD8+ T cell failure remain not well studied. Here we used a mouse melanoma model to study the interaction of growing tumor cells, innate immunity and CD8+ T cell responses induced by viral replication. Mouse model of melanoma (B16F10-OVA) and infections with arenaviruses. Growing B16F10-OVA cells did not induce systemic ablation of tumor specific CD8+ T cells. However, despite the presence of tumor-infiltrating CD8+ T cells, the anti-tumoral immune response was very limited. T cell anergy against the tumor was accompanied with a strong down-regulation of MHC-I on advanced tumors. LCMV infection restored the MHC class I expression, enhanced T cell function and lead to tumor regression. This study shows that tumor progression does not necessary lead to systemic exhaustion of the anti-tumoral CD8+ T cell response. Lack of innate signals is an additional reason for limited CD8+ T cell mediated cytotoxicity against the tumor.

immunology↗