Programmable Control in Extracellular Matrix-mimicking Polymer Hydrogels.

The extracellular matrix (ECM) and cells have a reciprocal relationship, one shapes the other and vice versa. One of the main challenges of synthetic material systems for developmental cell culturing, organoid and stem cell work includes the implementation of this reciprocal nature. The largest hurdle to achieve true cell-instructive materials in biomaterials engineering is a lack of spatial and temporal control over material properties and the display of bioactive signals compared to the natural cell environment. ECM-mimicking hydrogels have been developed using a wide range of polymers, assembly and cross-linking strategies. While our synthetic toolbox is larger than nature, often our systems underperform when compared to ECM systems with natural components like Matrigel. Material properties and three-dimensional structure ill-represent the three-dimensional ECM reciprocal nature and ligand presentation is an oversimplified version of the complexity found in nature. We hypothesize that the lack of programmable control in properties and ligand presentation forms the basis of this mismatch in performance and analyze the presence of control in current state of the art ECM-mimicking systems based on covalent, supramolecular and recombinant polymers. We conclude that through combining the dynamics of supramolecular materials, robustness from covalent systems and the programmable spatial control of bio-activation in recombinant ECM materials, the optimal synthetic artificial ECM could be assembled.

Multi-omics analysis identifies essential regulators of mitochondrial stress response in two wild-type C. elegans strains.

The mitochondrial unfolded protein response (UPRmt) is a promising pharmacological target for aging and age-related diseases. However, the integrative analysis of the impact of UPRmt activation on different signaling layers in animals with different genetic backgrounds is lacking. Here, we applied systems approaches to investigate the effect of UPRmt induced by doxycycline (Dox) on transcriptome, proteome, and lipidome in two genetically divergent worm strains, named N2 and CB4856. From the integrated omics datasets, we found that Dox prolongs lifespan of both worm strains through shared and strain-specific mechanisms. Specifically, Dox strongly impacts mitochondria, upregulates defense response, and lipid metabolism, while decreasing triglycerides. We further validated that lipid genes acs-2/20 and fat-7/6 were required for Dox-induced UPRmt and longevity in N2 and CB4856 worms, respectively. Our data have translational value as they indicate that the beneficial effects of Dox-induced UPRmt on lifespan are consistent across different genetic backgrounds through different regulators.

Chalcone synthase gene lineage diversification confirms allopolyploid evolutionary relationships of European rostrate violets.

Phylogenetic relationships among and within the subsections of the genus Viola are still far from resolved. We present the first organismal phylogeny of predominantly western European species of subsection Rostratae based on the plastid trnS-trnG intron and intergenic spacer and the nuclear low-copy gene chalcone synthase (CHS) sequences. CHS is a key enzyme in the synthesis of flavonoids, which are important for flower pigmentation. Genes encoding for CHS are members of a multigene family. In Viola, 3 different CHS copies are present. CHS gene lineages obtained confirmed earlier hypotheses about reticulate relationships between species of Viola subsection Rostratae based on karyotype data. Comparison of the CHS gene lineage tree and the plastid species phylogeny of Viola reconstructed in this study indicates that the different CHS copies present in Viola are the products of both recent and more ancient duplications.