Biology subjects

Burrows, S.

Publications and source records attributed to Burrows, S..

4 recordsLinked to original sources

bioRxiv2025

Network analysis of flowering time genes suggests regulatory changes among SOC1 orthologues in response to cold in Brassica napus

Flowering plants respond to multiple environmental and endogenous cues to determine the timing of their transition from the vegetative to floral state. Most of our knowledge of the gene regulatory network (GRN) controlling flowering time has been derived from the model plant Arabidopsis thaliana. This knowledge needs to be translated to crop plants to support the development of varieties that can be grown in different and rapidly changing climatic conditions. However, due to increased genome complexity and limited prior knowledge, translation into crops is not always straightforward. Here, we present a study of the GRN controlling flowering time in Brassica napus (oilseed rape), an allotetraploid crop that is a close relative of Arabidopsis. Using a comparative transcriptomics approach, we show that the majority of the orthologous gene pairs have similar expression dynamics over development between Arabidopsis and Brassica napus. Some genes, however, have experienced regulatory changes, with flowering time genes in Brassica napus having higher than average differences in their expression profiles from their Arabidopsis orthologues. Despite these differences, the inferred GRN for flowering in Brassica napus exhibits a similar network topology to the network known in Arabidopsis. This is likely due to preferential retention of these genes in higher paralogue numbers, which allows subtle changes in the regulation of individual paralogues, while still conserving the overall regulatory structure through evolution. We discover and present a detailed analysis of one such example where orthologues of SUPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) have similar expression patterns under normal conditions, but different dynamics under cold temperature conditions, suggesting possible subfunctionalisation among paralogues in response to temperature change.

plant biology↗

bioRxiv2025

PERM1 Gene Delivery via AAV Prevents Heart Failure in a Mouse Model of Pressure Overload

Heart failure with reduced ejection fraction (HFrEF) remains a leading cause of mortality worldwide. A hallmark of HFrEF is impaired cardiomyocyte contractility accompanied by disrupted mitochondrial bioenergetics; however, no current therapy targets both pathologies simultaneously. PERM1, a striated muscle-specific regulator of mitochondrial bioenergetics, is downregulated in HFrEF patients. We recently demonstrated that overexpression of PERM1 via adeno-associated virus 9 (AAV9-PERM1) enhances both cardiac contractility and mitochondrial biogenesis in C57BL/6 mice. In this study, we evaluated the therapeutic potential of AAV9-PERM1 in a pressure overload-induced mouse model of HFrEF. C57BL/6 mice were treated with either AAV9-PERM1 or control AAV9-GFP (1x1012 GC/mouse), followed by transverse aortic constriction (TAC) surgery. At 4 weeks post-TAC, control mice receiving AAV-GFP exhibited reduced left ventricular ejection fraction (LVEF), whereas AAV-PERM1 preserved LVEF at baseline levels. This cardioprotective effect was sustained through 8 weeks. Notably, AAV9-PERM1 completely abrogated TAC-induced cardiac hypertrophy and fibrosis. Mitochondrial analysis revealed that AAV9-PERM1 preserved mitochondrial DNA copy number and TFAM protein levels, both of which were reduced by TAC in control hearts. AAV9-PERM1 also improved mitochondrial respiration using pyruvate and octanoylcarnitine as substrates and prevented TAC-induced impairments in oxidative capacity. While PGC-1 expression remained unchanged in control TAC hearts, it was modestly yet significantly upregulated by AAV9-PERM1 in both sham and TAC groups. In addition, AAV9-PERM1 suppressed TAC-induced increases in O-GlcNAcylation, a stress-related posttranslational modification of proteins. Co-immunoprecipitation further revealed interactions of PERM1 with creatine kinase and troponin C, key proteins in ATP transduction and contractility, suggesting a functional coupling between mitochondrial energetics and contractility. In conclusion, AAV-PERM1 gene therapy effectively preserves cardiac function under pressure overload by maintaining mitochondrial biogenesis, respiration capacity and contractility. This study further suggests AAV-PERM1 as a promising therapeutic strategy for HFrEF.

physiology↗

bioRxiv2024

Rapid reprogramming and stabilisation of homoeolog expression bias in hexaploid wheat biparental populations

O_LIDifferences in the relative level of expression of homoeologs, known as homoeolog expression bias (HEB), are widely observed in allopolyploids. While the evolution of homoeolog expression bias through hybridisation has been characterised, on shorter timescales the extent to which homoeolog expression bias is preserved or altered between generations remains elusive. C_LIO_LIHere we use biparental mapping populations of hexaploid wheat (Triticum aestivum) with a common Paragon parent to explore the inheritance of homoeolog expression bias in the F5 generation. C_LIO_LIWe found that homoeolog expression bias is inherited for 26-27% of triads in both populations. Most triads ([~]70%) conserved a similar homoeolog expression bias pattern as one or both parents. Inherited patterns were largely driven by changes in the expression of one homoeolog, allowing homoeolog expression bias in subsequent generations to match parental expression. Novel patterns of homoeolog expression bias occurred more frequently in the biparental population from a landrace x elite cross, than in the population with two elite parents. C_LIO_LIThese results demonstrate that there is significant reprogramming and stabilisation of homoeolog expression bias within a small number of generations that differs significantly based on the parental lines used in the crossing. C_LI

plant biology↗

bioRxiv2024

Partial redundancy buffers deleterious effects of mutating DNA methyltransferase 1-1 (MET1-1) in polyploid wheat

DNA methylation is conserved across biological kingdoms, playing important roles in gene expression, transposable element silencing and genome stability. Altering DNA methylation could generate additional phenotypic variation for crop breeding, however the lethality of epigenetic mutants in crop species has hindered its investigation. Here, we exploit partial redundancy between homoeologs in polyploid wheat to generate viable mutants in the DNA methyltransferase 1-1 (MET1-1) gene with altered methylation profiles. In both Triticum turgidum (tetraploid wheat) and Triticum aestivum (hexaploid wheat) we identified clear segregation distortions of higher-order mutants (5/6 and 6/6 mutant met1-1 copies in hexaploid and 3/4 and 4/4 copies in tetraploid) when genotyping segregating seeds and seedlings, which we attribute to reduced transmission of null mutant gametes. We found that the reduced transmission occurred from both the maternal and paternal gametes, however, we did not detect any deleterious effects on pollen development. The loss of four or more functional copies of MET1-1 results in decreased CG methylation in hexaploid wheat. Changes to gene expression increase stepwise with the number of mutant alleles suggesting a dosage dependent effect. Finally, we identify heritable changes to flowering and awn phenotypes which segregate independently of MET1-1. Together our results demonstrate that polyploidy can be leveraged to generate quantitative changes to CG methylation without the lethal consequences observed in other crops, opening the potential to exploit novel epialleles in plant breeding.

plant biology↗