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Jüttner, J.

Publications and source records attributed to Jüttner, J..

2 recordsLinked to original sources

Pangenomic context reveals the extent of intraspecific plant NLR evolution

Nucleotide-binding leucine-rich repeat (NLR) proteins are a major component of the plant immune system, which directly or indirectly detect molecular signals of pathogen invasion. Despite their critical role, the processes by which NLR genes diversify remain poorly characterised due to the extraordinary sequence, structural, and regulatory variability of NLRs, even among closely related individuals. To understand the evolution of NLR diversity in Arabidopsis thaliana, we leverage graph-based methods to define pangenomic NLR neighbourhoods in 17 genetically diverse genomes. We integrate full-length transcript and transposable element information to exhaustively annotate all intact and degraded NLRs, enabling exploration of the processes that underpin the birth, death and maintenance of NLR diversity within a species. Our main finding is that many uncorrelated mutational processes create NLR diversity, and that there is no single metric that captures on its own the true extent of NLR structural and sequence variation. This immense diversity in plant immune system diversification allows populations to survive the constant onslaught of pathogens, not unlike vertebrate adaptive immunity, where variation is also generated by a variety of complementary mechanisms, albeit at the level of individuals.

plant biology↗

Cell type-focused compound screen in human organoids reveals molecules and pathways controlling cone photoreceptor death

Human organoids that mirror their corresponding organs in cell-type diversity present an opportunity to perform large-scale screens for compounds that protect disease-affected or damage healthy cell types. However, such screens have not yet been performed. Here, we generated 20,000 human retinal organoids with GFP-labeled cone photoreceptors. Since degeneration of cones is a leading cause of blindness, we induced cone death and screened 2,707 compounds with known targets, for those that saved cones or those that further damaged cones. We identified inhibitors of CK1 or MAPK11 that protected cones, HSP90 inhibitors that saved cones in the short term but damaged them in the longer term, and broad HDAC inhibition by many compounds that significantly damaged cones. This work provides a database for cone-damaging compounds and describes compounds that can be starting points to develop neuroprotection for cones in diseases such as macular degeneration.

neuroscience↗