Biology subjects

Field, R.

Publications and source records attributed to Field, R..

8 recordsLinked to original sources

bioRxiv2024

Integrative analysis of CAM photosynthesis reveals its impact on primary metabolism in Yucca

Crassulacean Acid Metabolism (CAM) is an adaptation that temporally separates carbon uptake at night from photosynthesis during the day. CAM has evolved repeatedly across vascular plants, as its emergence may depend on simple regulatory changes to deeply conserved metabolic pathways. Modern CAM research relies heavily on interpretation of transcriptomic data, though regulation occurs at multiple levels following transcription. Additionally, while most research to date has focused on a handful of genes and metabolites in the core CAM pathway, the co-option of conserved regulatory and functional genes is bound to have wide ranging effects on other aspects of primary metabolism. In this study, we integrate transcriptomic, proteomic, and metabolomic data to compare primary metabolism between the CAM species Yucca aloifolia and closely related C3 species, Y. filamentosa. We observe minimal correlation between protein abundance and mRNA expression, suggesting significant post-transcriptional regulation in CAM species. We also find evidence of shifts in gene expression and metabolite accumulation outside of the central CAM pathway suggesting that the shift to CAM has cascading effects across primary metabolism, especially nitrogen metabolism. Our findings provide insights into the metabolic shifts associated with CAM evolution and highlight the complexity of its regulation at multiple biological levels.

evolutionary biology↗

bioRxiv2023

Species abundances often conform to 'abundant-centre' patterns depending on dispersal capabilities

A shared goal within macroecology, biogeography and population ecology research is to understand biodiversity patterns and the processes driving them across spatial and taxonomic scales. A common approach to study macroecological patterns and processes involves developing and testing ecogeographical rules or hypotheses. The much-debated abundant-centre hypothesis posits that species abundances are highest in their range centres and decline towards their range edges. We perform the largest global test of the hypothesis to date, on 3,675 species, using 6,055,549 abundance observations. Using meta-analytical approaches, we summarised species-level abundance-distance correlations exploring the effects of dispersal-related species traits on abundance-distance relationships. Overall, animals did not follow abundant-centre patterns, whereas plants tended to. Larger-bodied mammals were more likely to conform to abundant-centre patterns, as were mammals and freshwater fishes from higher latitudes. Perennial life cycles and large range sizes were significant predictors of abundant-centre patterns in plants. Trees and shrubs with larger seeds showed more support for abundant-centre patterns. Accounting for species dispersal improves models of abundant-centre patterns across geographic space. Assuming abundant-centre patterns represent optimal equilibria within nature, our findings suggest that abundant-centre relationships are not a general ecological phenomenon but tend to manifest only in species with higher dispersal capabilities.

ecology↗

bioRxiv2023

Adipocyte lipin 1 is positively associated with metabolic health in humans and regulates systemic metabolism in mice.

Dysfunctional adipose tissue is believed to promote the development of hepatic steatosis and systemic insulin resistance, but many of the mechanisms involved are still unclear. Lipin 1 catalyzes the conversion of phosphatidic acid to diacylglycerol (DAG), the penultimate step of triglyceride synthesis, which is essential for lipid storage. Herein we found that adipose tissue LPIN1 expression is decreased in people with obesity compared to lean subjects and low LPIN1 expression correlated with multi-tissue insulin resistance and increased rates of hepatic de novo lipogenesis. Comprehensive metabolic and multi-omic phenotyping demonstrated that adipocyte-specific Lpin1-/- mice had a metabolically-unhealthy phenotype, including liver and skeletal muscle insulin resistance, hepatic steatosis, increased hepatic de novo lipogenesis, and transcriptomic signatures of nonalcoholic steatohepatitis that was exacerbated by high-fat diets. We conclude that adipocyte lipin 1-mediated lipid storage is vital for preserving adipose tissue and systemic metabolic health and its loss predisposes mice to nonalcoholic steatohepatitis.

physiology↗

bioRxiv2023

Widespread reductions in body size are paired with stable assemblage biomass.

Biotic responses to global change include directional shifts in organismal traits. Body size, an integrative trait that determines demographic rates and ecosystem functions, is often thought to be shrinking in the Anthropocene. Here, we assess the prevalence of body size change in six taxon groups across 5,032 assemblage time-series spanning 1960-2020. Using the Price equation to partition this change into within-species body size versus compositional changes, we detect prevailing decreases in body size through time. Change in assemblage composition contributes more to body size changes than within-species trends, but both components show substantial variation in magnitude and direction. The biomass of assemblages remains remarkably stable as decreases in body size trade-off with increases in abundance. One-Sentence SummaryVariable within-species and compositional trends combine into shrinking body size, abundance increases and stable biomass.

ecology↗

bioRxiv2021

Harnessing secretory pathway differences between HEK293 and CHO to rescue production of difficult to express proteins

Biologics represent the fastest growing group of therapeutics, but many advanced recombinant protein moieties remain difficult to produce. Here, we identify bottlenecks limiting expression of recombinant human proteins through a systems biology analysis of the transcriptomes of CHO and HEK293 during recombinant overexpression. Surprisingly, one third of the challenging human proteins displayed improved secretion upon host cell swapping from CHO to HEK293. While most components of the secretory machinery showed comparable expression levels in both expression hosts, genes with significant expression variation were identified. Among these, ATF4, SRP9, JUN, PDIA3 and HSPA8 were validated as productivity boosters in CHO. Further, more heavily glycosylated products benefitted more from the elevated activities of the N- and O-glycosyltransferases found in HEK293. Collectively, our results demonstrate the utilization of HEK293 for expression rescue of human proteins and suggest a methodology for identification of secretory pathway components improving recombinant protein yield in HEK293 and CHO.

systems biology↗

bioRxiv2020

Evolution from adherent to suspension - systems biology of HEK293 cell line development

The need for new safe and efficacious therapies has led to an increased focus on biologics produced in mammalian cells. The human cell line HEK293 has bio-synthetic potential for human-like production and is today used for manufacturing of several therapeutic proteins and viral vectors. Despite this increasing popularity there is still limited knowledge of the detailed genetic and composition of derivatives of this strain. Here we present a genomic, transcriptomic and metabolic gene analysis of six of the most widely used HEK293 cell lines. Changes in gene copy and expression between industrial progeny cell lines and the original HEK293 were associated with cellular component organization, cell motility and cell adhesion. Changes in gene expression between adherent and suspension derivatives highlighted switching in cholesterol biosynthesis and expression of five key genes (RARG, ID1, ZIC1, LOX and DHRS3), a pattern validated in 63 human adherent or suspension cell lines of other origin.

systems biology↗

bioRxiv2019

Diversification in evolutionary arenas -- assessment and synthesis

Understanding how and why rates of evolutionary diversification vary is a key issue in evolutionary biology, ecology, and biogeography, and the metaphorical concepts of adaptive radiation and evolutionary stasis describe two opposing aspects causing variation in diversification rates. Here we review the central concepts in the evolutionary diversification literature and synthesize these into a simple, general framework for studying rates of diversification and quantifying their underlying dynamics, which can be applied across clades and regions and across spatial and temporal scales. Our framework describes the diversification rate (d) as a function of the abiotic environment (a), the biotic environment (b) and clade-specific phenotypes or traits (c); thus d[~]a,b,c. We refer to the four components (a-d) and their interactions collectively as the Evolutionary Arena. We outline analytical approaches to this framework and present a case study on conifers, for which we parameterise the general model. We also discuss three conceptual examples: the Lupinus radiation in the Andes in the context of emerging ecological opportunity and fluctuating connectivity due to climatic oscillations; oceanic island radiations in the context of island formation and erosion; and biotically driven radiations of the Mediterranean orchid genus Ophrys. The results of the conifer case study are consistent with the long-standing scenario that low competition and high rates of niche evolution promote diversification. The conceptual examples illustrate how using the synthetic Evolutionary Arena framework helps to identify and structure future directions for research on evolutionary radiations. In this way, the Evolutionary Arena framework promotes a more general understanding of variation in evolutionary rates by making quantitative results comparable between case studies, thereby allowing new syntheses of evolutionary and ecological processes to emerge.

evolutionary biology↗

bioRxiv2018

Heterosynaptic Plasticity Normalizes Cortical Excitatory-Inhibitory Balance

Excitation in neural circuits must be carefully controlled by inhibition to regulate information processing and network excitability. During development, cortical inhibitory and excitatory inputs are initially mismatched but become co-tuned or balanced with experience. However, little is known about how excitatory-inhibitory balance is defined at most synapses, or the mechanisms for establishing or maintaining this balance at specific set-points. Here we show how coordinated long-term plasticity calibrates populations of excitatory/inhibitory inputs onto mouse auditory cortical pyramidal neurons. Pairing pre- and postsynaptic activity induced plasticity at paired inputs and different forms of heterosynaptic plasticity at the strongest unpaired synapses, which required minutes of activity and dendritic Ca2+ signaling to be computed. Theoretical analyses demonstrated how the relative rate of heterosynaptic plasticity could normalize and stabilize synaptic strengths to achieve any possible excitatory-inhibitory correlation. Thus excitatory-inhibitory balance is dynamic and cell-specific, determined by distinct plasticity rules across multiple excitatory and inhibitory synapses.

neuroscience↗