Biology subjects

Ferguson, M.

Publications and source records attributed to Ferguson, M..

4 recordsLinked to original sources

bioRxiv2018

The Immune Deficiency Pathway Attenuates Insulin Signaling to Protect Against Infection.

Immune and metabolic pathways collectively influence host responses to microbial invaders, and mutations in one pathway frequently disrupt activity in the other. We used the Drosophila model to characterize metabolic homeostasis in flies with modified Immune Deficiency (IMD) pathway activity. The IMD pathway is very similar to the mammalian Tumor Necrosis Factor-alpha pathway, a key regulator of vertebrate immunity and metabolism. We found that persistent activation of IMD resulted in hyperglycemia, depleted fat reserves, and developmental delays, implicating IMD in metabolic regulation. Consistent with this hypothesis, we found that imd mutants weigh more, are hyperlipidemic, and have impaired glucose tolerance. To test the importance of metabolic regulation for host responses to bacterial infection, we challenged insulin pathway mutants with lethal doses of several Drosophila pathogens. We found that loss-of-function mutations in the insulin pathway impacted host responses to infection in a manner that depends on the route of infection, and the identity of the infectious microbe. Combined, our results support a role for coordinated regulation of immune and metabolic pathways in host containment of microbial invaders.

immunology↗

bioRxiv2017

Leveraging Transcriptomics Data for Genomic Prediction Models in Cassava

BackgroundGenomic prediction models were, in principle, developed to include all the available marker information; with this approach, these models have shown in various crops moderate to high predictive accuracies. Previous studies in cassava have demonstrated that, even with relatively small training populations and low-density GBS markers, prediction models are feasible for genomic selection. In the present study, we prioritized SNPs in close proximity to genome regions with biological importance for a given trait. We used a number of strategies to select variants that were then included in single and multiple kernel GBLUP models. Specifically, our sources of information were transcriptomics, GWAS, and immunity-related genes, with the ultimate goal to increase predictive accuracies for Cassava Brown Streak Disease (CBSD) severity.\n\nResultsWe used single and multi-kernel GBLUP models with markers imputed to whole genome sequence level to accommodate various sources of biological information; fitting more than one kinship matrix allowed for differential weighting of the individual marker relationships. We applied these GBLUP approaches to CBSD phenotypes (i.e., root infection and leaf severity three and six months after planting) in a Ugandan Breeding Population (n = 955). Three means of exploiting an established RNAseq experiment of CBSD-infected cassava plants were used. Compared to the biology-agnostic GBLUP model, the accuracy of the informed multi-kernel models increased the prediction accuracy only marginally (1.78% to 2.52%).\n\nConclusionsOur results show that markers imputed to whole genome sequence level do not provide enhanced prediction accuracies compared to using standard GBS marker data in cassava. The use of transcriptomics data and other sources of biological information resulted in prediction accuracies that were nominally superior to those obtained from traditional prediction models.

genomics↗

bioRxiv2017

Genome-wide association mapping and genomic prediction unravels CBSD resistance in a Manihot esculenta breeding population

Cassava (Manihot esculenta Crantz), a key carbohydrate dietary source for millions of people in Africa, faces severe yield loses due to two viral diseases: cassava brown streak disease (CBSD) and cassava mosaic disease (CMD). The completion of the cassava genome sequence and the whole genome marker profiling of clones from African breeding programs (www.nextgencassava.org) provides cassava breeders the opportunity to deploy additional breeding strategies and develop superior varieties with both farmer and industry preferred traits. Here the identification of genomic segments associated with resistance to CBSD foliar symptoms and root necrosis as measured in two breeding panels at different growth stages and locations is reported. Using genome-wide association mapping and genomic prediction models we describe the genetic architecture for CBSD severity and identify loci strongly associated on chromosomes 4 and 11. Moreover, the significantly associated region on chromosome 4 colocalises with a Manihot glaziovii introgression segment and the significant SNP markers on chromosome 11 are situated within a cluster of nucleotide-binding site leucine-rich repeat (NBS-LRR) genes previously described in cassava. Overall, predictive accuracy values found in this study varied between CBSD severity traits and across GS models with Random Forest and RKHS showing the highest predictive accuracies for foliar and root CBSD severity scores.

genetics↗

bioRxiv2017

Integrated growth factor signaling promotes lung epithelial progenitor cell expansion and maintenance in mice and humans

The bud tip epithelium of the branching mouse and human lung contains multipotent progenitors that are able to self-renew and give rise to all mature lung epithelial cell types. The current study aimed to understand the developmental signaling cues that regulate bud tip progenitor cells in the human fetal lung, which are present during branching morphogenesis, and to use this information to induce a bud tip progenitor-like population from human pluripotent stem cells (hPSCs) in vitro. We identified that FGF7, CHIR-99021 and RA maintained isolated human fetal lung epithelial bud tip progenitor cells in an undifferentiated state in vitro, and led to the induction of a 3-dimensional lung-like epithelium from hPSCs. 3-dimensional hPSC-derived lung tissue was initially patterned, with airway-like interior domains and bud tip-like progenitor domains at the periphery. Epithelial bud tip-like domains could be isolated, expanded and maintained as a nearly homogeneous population by serial passaging. Comparisons between human fetal lung epithelial bud tip cells and hPSC-derived bud tip-like cells were carried out using immunostaining, in situ hybridization and transcriptome-wide analysis, and revealed that in vitro derived tissue was highly similar to native lung. hPSC-derived epithelial bud tip-like structures survived in vitro for over 16 weeks, could be easily frozen and thawed and maintained multi-lineage potential. Furthermore, hPSC-derived epithelial bud tip progenitors successfully engrafted in the proximal airways of injured immunocompromised NSG mouse lungs, where they persisted for up to 6 weeks and gave rise to several lung epithelial lineages.

developmental biology↗