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Biology subjects

Boden, S.

Publications and source records attributed to Boden, S..

7 recordsLinked to original sources

Relyophilized collagen scaffold to improve handling and small molecule loading

Tissue engineering scaffolds such as collagen-based biomaterials have long been used to mimic native extracellular matrix in a wide range of regenerative applications. Their high porosity, tunable degradation and mechanics, and cell adhesion sites provide a structure upon which cells can grow and differentiate, while they also have the potential to act as carriers for loading and release of biomolecules to aid in healing. Here we describe the inclusion of a second lyophilization step in the fabrication process to enable improved loading efficiency of bone morphogenic protein 2 as well as increased ease of end-user handling. We report mineralized collagen scaffolds demonstrate maintained microarchitecture and mechanical properties post-relyophilization with reduced variability in biomolecule loading. Relyophilization allows consistent loading and release profiles and suggests the potential to improve the translational potential of collagen scaffold biomaterials for regenerative medicine applications.

bioengineering↗

Multi-omics integration at cell type resolution uncovers gene-metabolite mechanisms underlying osteoarthritis heterogeneity

Metabolic dysregulation is an important factor for osteoarthritis pathogenesis, but comprehensive studies of underlying mechanisms and pathways are rare. We analyzed newly generated metabolomics data on bone marrow from 119 osteoarthritis patients, along with single-cell transcriptomics data to reconstruct networks of gene-metabolite associations at cell type resolution. Hubs of these networks - cell type-specific as well as pan-cell type hubs - revealed key molecular factors of osteoarthritis heterogeneity. Systems-level analysis of hubs revealed major roles for glycerophospholipid, glycerolipid and sphingolipid metabolism pathways, along with lipid signaling. We used Machine Learning models of gene-metabolite relationships to discover cell types most relevant to each metabolite. Integrative analysis of disease severity scores along with multi-omics data revealed a shift in specific immune cell subtypes in low versus high grade disease. We conclude that leveraging gene-metabolite covariation in a patient cohort can uncover underlying molecular mechanisms, overcoming the challenges posed by high dimensionality of multi-omics data.

bioinformatics↗

Spatial transcriptomics identifies distinct domains regulating yield-related traits of the wheat ear

Cereal inflorescences are complex, highly ordered structures composed of grain-producing florets that form within specialised branches called spikelets. The spikelets of wheat are arranged in two alternating rows along a central rachis, in a pattern determined during early reproductive development. While several genes that control spikelet development have been identified, the molecular processes that regulate their morphology and the formation of supporting structures, such as meristems and the rachis, remain poorly understood. Here, we used spatial transcriptomics to investigate the dynamic transcriptional landscape of a wheat inflorescence during spikelet development. We identified two spatially distinct regions that regulate spikelet architecture, including a primordium region characterised by RAMOSA2 activity, and a boundary region that expresses ALOG1 and known regulators of bract suppression. Developmental assays indicate that spikelets differentiate from meristematic regions, which is accompanied by formation of central vascular regions of the rachis and inflorescence base that express genes controlling spikelet number. The combined spatial transcriptome and genetic data reveal key regulators of spikelet development, including target genes for improving spikelet number and yield.

plant biology↗

Fungal pathogens exposed - genomic and phenotypic insights into Candida auris and its relatives of the Candida haemulonii species complex

Candida auris showed the world the ability of fungi to rapidly emerge as an urgent threat to public health. Close relatives of the Candida haemulonii complex exhibit also a similar multi-drug resistant nature and are increasingly reported as nosocomial pathogens. Here, we analyze both complete genomes assemblies and extensive phenotypic data for the five C. auris clades and pathogenic and non-pathogenic species related to the C. haemulonii species complex. First, we resolved the phylogeny of the species complex. Next, comparing C. auris to its pathogenic and non-pathogenic relatives we identified a pathogenic potential for the whole C. haemulonii species complex by shared gene content and phenotypic traits linked to drug resistance and virulence. In vivo virulence assays using the Galleria mellonella fungal infection model show that C. auris strains are significantly more virulent than any of the sibling species in the C. haemulonii complex. Phenotypic analysis links the increased virulence of C. auris to a more stress resistant phenotype compared to its siblings.

microbiology↗

Genotypic and resistance profile analysis of two oat crown rust differential sets urge coordination and standardisation

Puccinia coronata f. sp. avenae (Pca) is the causal agent of the disease known as crown rust which represents a bottleneck in oat production worldwide. Characterisation of pathogen populations often involves race (pathotype) assignments using differential sets, which are not uniform across countries. This study compared virulence profiles of 25 Pca isolates from Australia using two host differential sets, one from Australia and one from the USA. These differential sets were also genotyped using DArT sequencing technology. Phenotypic and genotypic discrepancies were detected on eight out of 29 common lines between the two sets, indicating that pathogen race assignments based on those lines are not comparable. To further investigate molecular markers that could assist in the stacking of rust resistance genes important for Australia, four published Pc91-linked markers were validated across the differential sets and then screened across a collection of 150 oat cultivars. Drover, Aladdin, and Volta were identified as putative carriers of the Pc91 locus. This is the first report to confirm that the cultivar Volta carries Pc91 and demonstrates the value of implementing molecular markers to characterise materials in breeding pools of oat. Overall, our findings highlight the necessity of examining seed stocks using pedigree and molecular markers to ensure seed uniformity and bring robustness to surveillance methodologies.

plant biology↗

A scalable phenotyping approach for female floral organ development and senescence in the absence of pollination in wheat

In the absence of pollination, female reproductive organs senesce leading to an irrevocable loss in the reproductive potential of the flower and directly affecting seed set. In self-pollinating crops like wheat (Triticum aestivum), the post-anthesis viability of the unpollinated carpel has been overlooked, despite its importance for hybrid seed production systems. To advance our knowledge of carpel development in the absence of pollination, we created a relatively high-throughput phenotyping approach to quantify stigma and ovary morphology. We demonstrate the suitability of the approach, which is based on light microscopy imaging and machine learning, for the detailed study of floral organ traits in field grown plants using both fresh and fixed samples. We show that the unpollinated carpel undergoes a well-defined initial growth phase, followed by a peak phase (in which stigma area reaches its maximum and the radial expansion of the ovary slows), and a final deterioration phase. These developmental dynamics were largely consistent across years and could be used to classify male sterile cultivars, however the absolute duration of each phase varied across years. This phenotyping approach provides a new tool for examining carpel morphology and development which we hope will help advance research into this field and increase our mechanistic understanding of female fertility in wheat.

plant biology↗

Evolution of the bread wheat D-subgenome and enriching it with diversity from Aegilops tauschii

Aegilops tauschii, the diploid wild progenitor of the D-subgenome of bread wheat, constitutes a reservoir of genetic diversity for improving bread wheat performance and environmental resilience. To better define and understand this diversity, we sequenced 242 Ae. tauschii accessions and compared them to the wheat D-subgenome. We characterized a rare, geographically-restricted lineage of Ae. tauschii and discovered that it contributed to the wheat D-subgenome, thereby elucidating the origin of bread wheat from at least two independent hybridizations. We then used k-mer-based association mapping to identify discrete genomic regions with candidate genes for disease and pest resistance and demonstrated their functional transfer into wheat by transgenesis and wide crossing, including the generation of a library of synthetic hexaploids incorporating diverse Ae. tauschii genomes. This pipeline permits rapid trait discovery in the diploid ancestor through to functional genetic validation in a hexaploid background amenable to breeding.

plant biology↗