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Downey, F.

Publications and source records attributed to Downey, F..

2 recordsLinked to original sources

Transcriptional signatures associated with waterlogging stress responses and aerenchyma formation in barley root tissue

The negative impact of soil waterlogging on crop production is expected to increase due higher frequencies of extreme rainfall events arising from climate change. Consequently, understanding the molecular mechanisms that enable plants to mitigate waterlogging stress is critical for breeding programmes, particularly in the case of waterlogging-susceptible crop species, such as barley (Hordeum vulgare). Aerenchyma formation is a key morphological adaptation allowing plants to cope with waterlogging stress and hypoxic conditions, however, the genetic regulation of its development in barley remains largely unresolved. In this study, two barley cultivars with contrasting waterlogging tolerance (Franklin and Yerong) were subjected to waterlogging stress, followed by analysis of phenotypic traits including root aerenchyma formation, and transcriptomic profiling of root tissue samples. Differential expression analyses identified genes transcriptionally responsive to 24 and 72 h of waterlogging in both cultivars, and highlighted metabolic adaptations, regulation of ROS signalling and management of stress responses as key elements of the waterlogging response. The results revealed large intra-individual variations in root aerenchyma formation, and these variations were exploited to isolate 81 candidate aerenchyma-associated genes from the generated RNA-seq datasets. Network analyses suggest the involvement of the DNA damage response gene, DRT100 and cell wall modifying genes, XHT16 and XHT15 as regulatory hub genes in aerenchyma formation. Collectively, the generated data provide insights into transcriptional signatures associated with the barley root responses to waterlogging and aerenchyma formation, informing our understanding of strategies that plants employ to cope with the negative impacts of heavy rainfall.

plant biology↗

Selective capture of circulating metastatic cancer cell clusters from lung cancer patients reveals a unique genomic profile that identifies anti-metastatic molecular therapeutic targets.

Metastasis remains the leading cause of cancer deaths worldwide and lung cancer, known for its highly metastatic progression, remains among the most lethal of malignancies. The heterogeneous genomic profile of lung cancer metastases is often unknown. Since different metastatic events can selectively spread to multiple organs, strongly suggests more studies are needed to understand and target these different pathways. Unfortunately, access to the primary driver of metastases, the metastatic cancer cell clusters (MCCCs), remains difficult and limited. These metastatic clusters have been shown to be 100-fold more tumorigenic than individual cancer cells. Capturing and characterizing MCCCs is a key limiting factor in efforts to help treat and ultimately prevent cancer metastasis. Elucidating differentially regulated biological pathways in MCCCs will help uncover new therapeutic drug targets to help combat cancer metastases. We demonstrate a novel, proof of principle technology, to capture MCCCs directly from patients whole blood. Our platform can be readily tuned for different solid tumor types by combining a biomimicry-based margination effect coupled with immunoaffinity to isolate MCCCs. Adopting a selective capture approach based on overexpressed CD44 in MCCCs provides a methodology that preferentially isolates them from whole blood. Furthermore, we demonstrate a high capture efficiency of more than 90% when spiking MCCC-like model cell clusters into whole blood. Characterization of the captured MCCCs from lung cancer patients by immunofluorescence staining and genomic analyses, suggests highly differential morphologies and genomic profiles., This study lays the foundation to identify potential drug targets thus unlocking a new area of anti-metastatic therapeutics.

cancer biology↗