Biology subjects

Taylor, L. J.

Publications and source records attributed to Taylor, L. J..

6 recordsLinked to original sources

bioRxiv2024

GIGANTEA is required for circadian rhythms in wheat

GIGANTEA (GI) is a plant-specific protein that functions in many physiological processes and signalling networks. In Arabidopsis, GI has a central role in circadian oscillators regulating the abundance of ZEITLUPE and TIMING OF CAB EXPRESSION 1 proteins and is essential for photoperiodic regulation of flowering. We have investigated how ortholgues of this component of Arabidopsis circadian oscillators contributes to circadian rhythms and yield traits, including heading (flowering) in wheat. We find that GI is a core component of wheat circadian oscillators that is necessary to maintain robust oscillations in chlorophyll fluorescence and circadian oscillator transcript abundance. Predicted lack of functional GI results in later flowering in wheat in both long days and short days in controlled environment conditions. Our results support and extend previous work which suggests that the pathways by which photoperiodism regulates flowering are not fully conserved between Arabidopsis and wheat. Understanding the molecular basis for photoperiodism in wheat is important for breeders looking to manipulate flowering time and develop new elite, high yielding cultivars. HighlightGIGANTEA is required for robust circadian oscillations in wheat and regulates heading, most likely through a PHOTOPERIOD-1-dependent pathway.

plant biology↗

bioRxiv2023

Light and temperature regulate m6A-RNA modification to regulate growth in plants

N6-methyladenosine is a highly dynamic, abundant mRNA modification which is an excellent potential mechanism for fine tuning gene expression. Plants adapt to their surrounding light and temperature environment using complex gene regulatory networks. The role of m6A in controlling gene expression in response to variable environmental conditions has so far been unexplored. Here, we map the transcriptome-wide m6A landscape under various light and temperature environments. Identified m6A-modifications show a highly specific spatial distribution along transcripts with enrichment occurring in 5UTR regions and around transcriptional end sites. We show that the position of m6A modifications on transcripts might influence cellular transcript localization and the presence of m6A-modifications is associated with alternative polyadenylation, a process which results in multiple RNA isoforms with varying 3UTR lengths. RNA with m6A-modifications exhibit a higher preference for shorter 3UTRs. These shorter 3UTR regions might directly influence transcript abundance and localization by including or excluding cis-regulatory elements. We propose that environmental stimuli might change the m6A landscape of plants as one possible way of fine tuning gene regulation through alternative polyadenylation and transcript localization.

plant biology↗

bioRxiv2021

Wheat EARLY FLOWERING3 is a dawn-expressed circadian oscillator component that regulates heading date

Using an eight-parent Multiparent Advanced Generation Inter-Cross (MAGIC) population we investigated how variation at circadian clock-associated genes contributes to the regulation of heading date in UK and European winter wheat varieties. We identified homoeologues of EARLY FLOWERING 3 (ELF3) as candidates for the Earliness per se (Eps) D1 and B1 loci in field conditions. We confirmed that a SNP within the coding region of TaELF3-B1 is a candidate polymorphism underlying the Eps-B1 locus. We found that a reported deletion at the Eps-D1 locus encompassing TaELF3-D1, is instead a novel allele that lies within an introgression region containing an inversion relative to the Chinese Spring D genome. Using T. turgidum cv. Kronos carrying loss of function alleles of TtELF3 we show that ELF3 does regulate heading by demonstrating that the loss of a single ELF3 homoeologue was sufficient to alter heading date. These studies demonstrated that ELF3 forms part of the circadian oscillator but loss of all homoeologues was required to affect circadian rhythms. Similarly, loss of functional LUX ARRHYTHMO (LUX) in T. aestivum, an orthologue of a protein partner of Arabidopsis ELF3, severely disrupted circadian rhythms. ELF3 and LUX transcripts are not co-expressed at dusk suggesting the structure of the wheat circadian oscillator might differ to that of Arabidopsis. Our demonstration that alteration to ELF3 homoeologues can affect heading date separate from effects on the circadian oscillator suggests a role for ELF3 in cereal photoperiodic responses that could be selected for, without pleiotropic deleterious alterations to circadian rhythms.

plant biology↗

bioRxiv2021

Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia

Stress-adaptive mechanisms enable tumor cells to overcome metabolic constraints in nutrient and oxygen poor tumors. Aspartate is an endogenous metabolic limitation under hypoxic conditions, but the nature of the adaptive mechanisms that contribute to aspartate availability and hypoxic tumor growth are poorly understood. Here, using a combination of metabolomics and CRISPR-based genetic screens, we identify GOT2-catalyzed mitochondrial aspartate synthesis as an essential metabolic dependency for the proliferation of pancreatic tumor cells under hypoxic culture conditions. In contrast, GOT2-catalyzed aspartate synthesis is dispensable for pancreatic tumor formation in vivo. The dependence of pancreatic tumor cells on aspartate synthesis is bypassed in part by a hypoxia-induced potentiation of extracellular protein scavenging via macropinocytosis. This effect is mutant KRas-dependent, and is mediated by hypoxia inducible factor 1 (HIF1A) and its canonical target carbonic anhydrase-9 (CA9) through the cooption of the bicarbonate-macropinocytosis signaling axis. Our findings reveal high plasticity of aspartate metabolism and define an adaptive regulatory role for macropinocytosis by which mutant KRas tumors can overcome nutrient deprivation under hypoxic conditions.

cancer biology↗

bioRxiv2020

Circulating bile acid levels direct sex-differences in liver cancer development

Hepatocellular carcinoma (HCC), the most common liver cancer, exhibits a higher incidence in males. Here, we report that mice lacking the bile acid regulators, Farnesoid X Receptor (FXR) and Small Heterodimer Partner (SHP), recapitulate the sex difference in liver cancer risk. Since few therapeutic options are available, we focused on understanding the intrinsic protection afforded to female livers. Transcriptomic analysis in control and FXR and SHP double knockout livers identified female-specific changes in metabolism, including amino acids, lipids, and steroids. We examined if the obtained transcriptomic signatures correlate with the survival outcomes for HCC patients to assess the translational potential of this murine HCC model. Gene signatures that are unique to the knockout females correspond with low-grade tumors and better survival. Ovariectomy blunts the metabolic changes in female livers and promotes tumorigenesis that, intriguingly, coincides with increases in serum bile acid (BA) levels. Despite similar genetics, we found higher serum BA concentrations in males, whereas female knockout mice excreted more BAs. Decreasing enterohepatic BA recirculation using cholestyramine, an FDA-approved resin, dramatically reduced the liver cancer burden in male mice. Overall, we reveal that sex-specific BA metabolism leading to lower circulating BA concentration protects female livers from developing cancer. Thus, targeting BA excretion may be a promising therapeutic strategy against HCC. SignificanceWe show that female-specific gene profiles identified in Fxr-/-, Shp-/- double knockout (DKO) mice correlate with better outcomes for HCC patients and uncover sex differences in circulation and excretion of bile acid. Overall, we demonstrate that increasing (ovariectomy or chemical injury) or decreasing (pharmacologically with FDA-approved resin) serum bile acids, not hepatic bile acids, promoted or alleviated liver cancer burden.

cancer biology↗

bioRxiv2018

Sunbeam: a pipeline for next-generation metagenomic sequencing experiments

BackgroundAnalysis of mixed microbial communities using metagenomic sequencing experiments requires multiple preprocessing and analytical steps to interpret the microbial and genetic composition of samples. Analytical steps include quality control, adapter trimming, host decontamination, metagenomic classification, read assembly, and alignment to reference genomes. ResultsWe present a modular and user-extensible pipeline called Sunbeam that performs these steps in a consistent and reproducible fashion. It can be installed in a single step, does not require administrative access to the host computer system, and can work with most cluster computing frameworks. We also introduce Komplexity, a software tool to eliminate potentially problematic, low-complexity nucleotide sequences from metagenomic data. Unique components of the Sunbeam pipeline include direct analysis of data from NCBI SRA and an easy-to-use extension framework that enables users to add custom processing or analysis steps directly to the workflow. The pipeline and its extension framework are well documented, in routine use, and regularly updated. ConclusionsSunbeam provides a foundation to build more in-depth analyses and to enable comparisons in metagenomic sequencing experiments by removing problematic low complexity reads and standardizing post-processing and analytical steps. Sunbeam is written in Python using the Snakemake workflow management software and is freely available at github.com/sunbeam-labs/sunbeam under the GPLv3.

bioinformatics↗