Biology subjects

Locke, J.

Publications and source records attributed to Locke, J..

3 recordsLinked to original sources

bioRxiv2018

Widespread inter-individual gene expression variability in Arabidopsis thaliana

A fundamental question in biology is how gene expression is regulated to give rise to a phenotype. However, transcriptional variability is rarely considered and could influence the relationship between genotype and phenotype. It is known in unicellular organisms that gene expression is often noisy rather than uniform and this has been proposed to be beneficial when environmental conditions are unpredictable. However, little is known about transcriptional variability in plants. Using transcriptomic approaches, we analysed gene expression variability between individual Arabidopsis thaliana plants growing in identical conditions over a 24 hour time-course. We identified hundreds of genes that exhibit high inter-individual variability and found that many are involved in environmental responses. We also identified factors that might facilitate gene expression variability, such as gene length, the number of transcription factors regulating the genes and the chromatin environment. These results shed new light on the impact of transcriptional variability in gene expression regulation in plants.

plant biology↗

bioRxiv2018

Escherichia coli can survive stress by noisy growth modulation

Gene expression can be noisy1,2, as can the growth of single cells3,4. Such cell-to-cell variation has been implicated in survival strategies for bacterial populations5-7. However, it remains unclear how single cells couple gene expression with growth to implement these survival strategies. Here we show how noisy expression of a key stress response regulator, rpoS8, allows E. coli to modulate its growth dynamics to survive future adverse environments. First, we demonstrate that rpoS has a long-tailed distribution of expression in an unstressed population of cells. We next reveal how a dynamic positive feedback loop between rpoS and growth rate produces multi-generation rpoS pulses, which are responsible for the rpoS heterogeneity. We do so experimentally with single-cell, time-lapse microscopy9 and microfluidics10 and theoretically with a stochastic model11,22. Finally, we demonstrate the function of the coupling of heterogeneous rpoS activity and growth. It enables E. coli to survive oxidative attack by causing prolonged periods of slow growth. This dynamic phenotype is captured by the rpoS-growth feedback model. Our synthesis of noisy gene expression, growth, and survival paves the way for further exploration of functional phenotypic variability.

systems biology↗

bioRxiv2017

A common allele in FGF21 associated with preference for sugar consumption lowers body fat in the lower body and increases blood pressure

Fibroblast Growth Factor 21 (FGF21) is a hormone that induces weight loss in model organisms. These findings have led to trials in humans of FGF21 analogues with some showing weight loss and lipid lowering effects. Recent genetic studies have shown that a common allele in the FGF21 gene alters the balance of macronutrients consumed but there was little evidence of an effect on metabolic traits. We studied a common FGF21 allele (A:rs838133) in 451,099 people from the UK Biobank study. We replicated the association between the A allele and higher percentage carbohydrate intake. We then showed that this allele is more strongly associated with body fat distribution, with less fat in the lower body, and higher blood pressure, than it is with BMI, where there is only nominal evidence of an effect. These human phenotypes of naturally occurring variation in the FGF21 gene will inform decisions about FGF21s therapeutic potential.

genetics↗