Biology subjects

Foster, G.

Publications and source records attributed to Foster, G..

3 recordsLinked to original sources

bioRxiv2020

Rapid ageing and species identification of natural mosquitoes for malaria surveillance

The malaria parasite, which is transmitted by several Anopheles mosquito species, requires more time to reach its human-transmissible stage than the average lifespan of a mosquito. Monitoring the species-specific age structure of mosquito populations is critical to evaluating the impact of vector control interventions on malaria risk. We developed a rapid, cost-effective surveillance method based on deep learning of mid-infrared spectra of mosquitoes cuticle that simultaneously identifies the species and the age of three main malaria vectors, in natural populations. Using over 40,000 ecologically and genetically diverse females, we could speciate and age grade An. gambiae, An. arabiensis, and An. coluzzii with up to 95% accuracy. Further, our model learned the age of new populations with minimal sampling effort and detected the impact of control interventions on simulated mosquito populations, measured as a shift in their age structures. We anticipate our method to be applied to other arthropod vector-borne diseases.

zoology↗

bioRxiv2020

Cyclical Regression Covariates remove the major confounding effect of cyclical developmental gene expression with strain-specific drug response in the malaria parasite Plasmodium falciparum

BackgroundThe cyclical nature of parasite gene expression in the intraerythrocytic development cycle (IDC) in human blood confounds the accurate detection of specific transcriptional differences due to drug resistance in Plasmodium falciparum. Here, we propose the use of cyclical regression covariates to eliminate the major confounding of developmentally driven transcriptional changes with changes due to drug response. We show that elimination of this confounding can reduce both Type I and Type II errors, and demonstrate the effect of approach on real data. ResultsWe apply this method to two publicly available datasets, and demonstrate its ability to reduce the potential confounding of differences in expression due the species-specific intraerythrocytic development cycle from strain-specific differences in drug response. We show that the application of cyclical regression covariates has minimal impact on the pool of transcripts identified as significantly different in a dataset generated from single timepoint clinical blood samples with low variance for developmental stage and a profound impact on another clinical data set with more variance among the samples for developmental stage. ConclusionsCyclical regression covariates have immediate application to studies where in-vitro synchronization of all samples to the same developmental timepoint is not feasible, primarily parasite transcriptome sequencing direct from clinical blood samples, a widely used approach to frontline detection of emerging drug resistance.

genomics↗

bioRxiv2019

Stat2 loss disrupts damage signalling and is protective in acute pancreatitis

Severity of sterile inflammation, as seen in acute pancreatitis, is determined by damage-sensing receptors, signalling cascades and cytokine production. Stat2 is a type I interferon signalling mediator that also has interferon-independent roles in murine lipopolysaccharide-induced NF-{kappa}B-mediated sepsis. However its role in sterile inflammation is unknown. We hypothesised that Stat2 determines severity of non-infective inflammation in the pancreas.\n\nWild type (WT) and Stat2-/- mice were injected intraperitoneally with cerulein or L-arginine. Specific cytokine-blocking antibodies were used in some experiments. Pancreata and blood were harvested 1h and 24h after the final dose of cerulein and up to 96h post L-arginine. Whole-tissue phosphoproteomic changes were assessed using label-free mass spectrometry. Tissue-specific Stat2 effects were studied in WT/Stat2-/- bone-marrow chimera and using Cre-lox recombination to delete Stat2 in pancreatic and duodenal homeobox 1(Pdx1)-expressing cells.\n\nStat2-/- mice were protected from cerulein- and L-arginine-induced pancreatitis. Protection was independent of type I interferon signalling. Stat2-/- mice had lower cytokine levels including TNF and IL-10 and reduced NF-kB nuclear localisation in pancreatic tissue compared to WT. Inhibition of TNF improved (inhibition of IL-10 worsened) cerulein-induced pancreatitis in WT but not Stat2-/- mice. Phosphoproteomics showed down-regulation of mitogen-activated protein kinase (MAPK) mediators but accumulation of Ser412-phosphorylated Tak1. Stat2 deletion in Pdx1-expressing acinar cells (Stat2flox/Pdx1-cre) reduced pancreatic TNF expression, but not histological injury or serum amylase. WT/Stat2-/- bone-marrow chimera were protected from pancreatitis irrespective of host or recipient genotype.\n\nStat2 loss results in disrupted signalling in pancreatitis, upstream of NF-{kappa}B in non-acinar and/or bone marrow derived cells.

immunology↗