Biology subjects

Gibson, M.

Publications and source records attributed to Gibson, M..

4 recordsLinked to original sources

bioRxiv2018

Adaptive strategies of the candidate probiotic E. coli Nissle in the mammalian gut

Probiotics are living microorganisms that are increasingly used as gastrointestinal therapeutics by virtue of their innate or engineered genetic function. Unlike abiotic therapeutics, probiotics can replicate in their intended site, subjecting their genomes and therapeutic properties to natural selection. By exposing the candidate probiotic E. coli Nissle (EcN) to the mouse gastrointestinal tract over several weeks, we uncovered the consequences of gut transit, inter-species competition, antibiotic pressure, and engineered genetic function on the processes under selective pressure during both within-genome and horizontal evolutionary modes. We then show the utility of EcN as a chassis for engineered function by achieving the highest reported reduction in serum phenylalanine levels in a mouse model of phenylketonuria using an engineered probiotic. Collectively, we demonstrate a generalizable pipeline which can be applied to other probiotic strains to better understand their safety and engineering potential.

evolutionary biology↗

bioRxiv2018

Evidence for genetic correlations and bidirectional, causal effects between smoking and sleep behaviours

IntroductionCigarette smokers are at increased risk of poor sleep behaviours. However, it is largely unknown whether these associations are due to shared (genetic) risk factors and/or causal effects (which may be bi-directional).\n\nMethodsWe obtained summary-level data of genome-wide association studies of smoking (smoking initiation (n=74,035), cigarettes per day (n=38,181) and smoking cessation (n=41,278)) and sleep behaviours (sleep duration and chronotype, or morningness) (n=128,266) and insomnia (n=113,006)). Using LD score regression, we calculated genetic correlations between smoking and sleep behaviours. To investigate causal effects, we employed Mendelian randomization (MR), both with summary-level data and individual level data (n=333,581 UK Biobank participants). For MR with summary-level data, individual genetic variants were combined with inverse-variance weighted meta-analysis, weighted median regression and MR Egger regression methods.\n\nResultsWe found positive genetic correlations between insomnia and smoking initiation (rg=0.27, 95% CI 0.06 to 0.49) and insomnia and cigarettes per day (rg=0.15, 0.01 to 0.28), and negative genetic correlations between sleep duration and smoking initiation (rg=-0.14, -0.26 to -0.01) and chronotype and smoking cessation (rg=-0.18, -0.31 to -0.06). MR analyses provided strong evidence that smoking more cigarettes per day causally decreases the odds of being a morning person, and weak evidence that insomnia causally increases smoking heaviness and decreases smoking cessation odds.\n\nConclusionsSmoking and sleep behaviours show moderate genetic correlation. Heavier smoking seems to causally affect circadian rhythm and there is some indication that insomnia increases smoking heaviness and hampers cessation. Our findings point to sleep as a potentially interesting smoking treatment target.

genetics↗

bioRxiv2017

An adaptable chromosome preparation methodology for use in invertebrate research organisms

BackgroundThe ability to efficiently visualize and manipulate chromosomes is fundamental to understand the genetic architecture of organisms. This can be challenging for many invertebrates because conventional chromosome preparation protocols deal primarily hypotonic conditions tailored for use with vertebrates and rely extensively on cultured cells which are rarely available for invertebrates. Hence, a simple and inexpensive chromosome preparation protocol, adaptable to multiple invertebrate model species is needed.\n\nResultsWe optimized a chromosome preparation protocol and applied it to several planarian species (Phylum: Platyhelminthes), the freshwater apple snail Pomacea canaliculata (Phylum: Mollusca), and the starlet sea anemone Nematostella vectensis (Phylum: Cnidaria). We showed that both mitotically active adult tissues and embryos can be used as sources of metaphase chromosomes, expanding the potential use of this technique to invertebrates lacking cell lines and/or with limited access to the complete life cycle. Simple hypotonic treatment with DI water was sufficient for karyotyping. The karyotypes we obtained allowed the identification of differences in ploidy and chromosome architecture among otherwise morphologically indistinguishable organisms, as in the case of a mixed population of planarians collected in the wild. Furthermore, we showed that in all tested organisms representing three different phyla, this protocol can be effectively coupled with downstream applications, such as chromosome fluorescent in situ hybridization.\n\nConclusionThe simple and inexpensive chromosome preparation protocol reported here can be readily adapted to new invertebrate research organisms in order to expand and accelerate the discovery of new biology in understudied branches of the tree of life.

developmental biology↗

bioRxiv2017

Investigating genetic correlations and causal effects between caffeine consumption and sleep behaviours

Study Objectives: Higher caffeine consumption has been linked to poorer sleep and insomnia complaints. We investigated whether these observational associations are the result of genetic risk factors influencing both caffeine consumption and poorer sleep, and/or whether they reflect (possibly bidirectional) causal effects. Methods: Summary-level data were available from genome-wide association studies (GWAS) on caffeine consumption (n=91,462), sleep duration, and chronotype (i.e., being a morning versus an evening person) (both n=128,266), and insomnia complaints (n=113,006). Linkage disequilibrium (LD) score regression was used to calculate genetic correlations, reflecting the extent to which genetic variants influencing caffeine consumption and sleep behaviours overlap. Causal effects were tested with bidirectional, two-sample Mendelian randomization (MR), an instrumental variable approach that utilizes genetic variants robustly associated with an exposure variable as an instrument to test causal effects. Estimates from individual genetic variants were combined using inverse-variance weighted meta-analysis, weighted median regression and MR Egger regression methods. Results: There was no clear evidence for genetic correlation between caffeine consumption and sleep duration (rg=0.000, p=0.998), chronotype (rg=0.086, p=0.192) or insomnia (rg=-0.034, p=0.700). Two-sample Mendelian randomization analyses did not support causal effects from caffeine consumption to sleep behaviours, or the other way around. Conclusions: We found no evidence in support of genetic correlation or causal effects between caffeine consumption and sleep. While caffeine may have acute effects on sleep when taken shortly before habitual bedtime, our findings suggest that a more sustained pattern of high caffeine consumption is likely associated with poorer sleep through shared environmental factors.

genetics↗