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Biology subjects

Gunter, J.

Publications and source records attributed to Gunter, J..

2 recordsLinked to original sources

A genomic and functional framework for the rapid domestication of the wild plant Chenopodium album

Global reliance on a small number of genetically uniform crops makes our food system increasingly vulnerable to pests, diseases, and climate change, highlighting the need to develop resilient local species as crops. Chenopodium album, a stress-tolerant, protein-rich wild plant whose seeds were part of prehistoric Northern European diets and whose leaves are still foraged worldwide, remains undomesticated despite its agrifood potential. We established a Danish collection of 143 accessions and combined seed metabolomics, ploidy assessment and genomics to uncover the molecular basis of key nutritional and anti-nutritional traits. Seed profiling revealed substantial variation in protein content (14-22%), comparable to or higher than major crops, and 16 distinct triterpenoid saponins, which are widespread bitter and anti-nutritional compounds. Seed production of field-grown lines reached up to 1.5 t/ha in trials conducted in Denmark, demonstrating promising yield potential. A high-quality tetraploid genome of a low-saponin line was assembled and contrasted with resequencing of a diploid high-saponin line in order to uncover the genetic basis of saponin variation in C. album. Comparative genomic, phylogenetic, and transcriptomic analyses identified structural variants and candidate genes associated with saponin biosynthesis, and functional validation confirmed the coordinated activity of a {beta}-amyrin synthase, three CYP716 cytochromes P450, and a glucuronosyltransferase that reconstitute the core C. album saponin pathway. Together, these results define the genomic and biochemical foundation of C. album, establishing a platform for its rapid domestication as a locally adapted, high-protein seed crop and a model for translating wild plant diversity into future food security.

plant biology↗

Glycogen phosphorylase inhibition alongside taxol chemotherapy synergistically elicits ferroptotic cell death in clear cell ovarian and kidney cancers

BackgroundClear cell carcinomas (CCCs) are a distinct histopathological subtype defined by a clear cytoplasm comprised of glycogen and lipids and characterised by poor prognosis and widespread chemoresistance. In the present work we investigate glycogen metabolism as a targetable modality for these cancers. Methods and ResultsAdopting the indole carboxamide site pan-glycogen phosphorylase inhibitor CP91149 against clear cell ovarian and renal cancer cell line models, we note antiproliferative and antimigratory effects, as well as energetic stress reflected by reduced ATP pools and increased superoxide-derived reactive oxygen species. Following this, using the agent alongside standard of care chemotherapies for clear cell ovarian (ccOC) and renal cell carcinoma (ccRCC), we note specific synergy with microtubule disrupting chemotherapy paclitaxel, a phenomenon retained in ccOC lines made stably resistant to paclitaxel. Rescue experiments, as well as phenotypic assays suggest that combination-treated cells undergo ferroptotic cell death. We postulate this synergistic efficacy to arise from subjecting the already hypersensitive clear cell cancers to the mitochondrial stress elicited by taxol chemotherapy alongside the oxidative stress augured by glycogen phosphorylase inhibition. ConclusionsGiven that CCCs are widely chemoresistant, the present work potentially presents a novel therapeutic avenue for this shared histotype.

cancer biology↗