Biology subjects

Matthews, B. J.

Publications and source records attributed to Matthews, B. J..

4 recordsLinked to original sources

bioRxiv2018

The ion channel ppk301 controls freshwater egg-laying in the mosquito Aedes aegypti

Aedes aegypti mosquitoes are deadly vectors of arboviral pathogens including Zika, dengue, and yellow fever, and breed in containers of freshwater associated with human habitation1,2. Female Ae. aegypti lay eggs near freshwater because larval and pupal stages are aquatic3. They use volatile cues to locate water at a distance4, while at close-range they contact water to evaluate its suitability for egg-laying4-7. High salinity is lethal to mosquito offspring and therefore correctly laying eggs in freshwater is a crucial parenting decision made by female mosquitoes. Here we show that the DEG/ENaC channel8-10 ppk301 is required for mosquitoes to exploit freshwater egg-laying substrates. When ppk301 mutant females contact water, they do not lay eggs as readily as wild-type animals and are more likely to make aberrant decisions between freshwater and saltwater at concentrations that impair offspring survival. We used a CRISPR-Cas9-based genetic knock-in strategy combined with the Q-binary transactivator system11 to build genetic tools for labelling and imaging neurons in the mosquito. We found that ppk301 is expressed in sensory neurons in legs and proboscis, appendages that directly contact water, and that ppk301-expressing neurons project to central taste centres. Using in vivo calcium imaging with the genetically-encoded calcium sensor GCaMP6s12, we found that ppk301-expressing cells respond to water but, unexpectedly, also to salt. This suggests that ppk301 is instructive for egg-laying at low salt concentrations but that a ppk301-independent pathway is responsible for inhibiting egg-laying at high salt concentrations. Water is a key resource for insect survival and understanding how mosquitoes interact with water to control different behaviours is an opportunity to study the evolution of chemosensory systems. The new genetic tools described here will enable direct study of not only egg-laying, but also other behaviours in mosquitoes that influence disease transmission and enable comparative studies of insect biology more broadly.

neuroscience↗

bioRxiv2018

Insulation of gene expression by CTCF and cohesin-based subTADs (ubiquitous intra-TAD loop structures) in mouse liver

CTCF and cohesin are key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. Here, we present a computational method to identify cohesin-and-CTCF binding sites that form intra-TAD DNA loops (subTADs). We show that predicted subTAD anchors are structurally indistinguishable from those of TADs regarding their binding partners, sequence conservation, and resistance to cohesin knockdown; further, the subTAD loops retain key functional features of TADs, including insulation of chromatin contacts, blockage of repressive histone mark spread, and ubiquity across tissues. We propose that subTADs form by the same loop extrusion mechanism as larger loops, and that their shorter length enables finer regulatory control over gene expression. 4C-seq analysis using an Alb promoter viewpoint illustrates the role of subTADs in restricting enhancer-promoter interactions. These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization, and demonstrate that distal enhancer insulation by subTADs is widespread.

genomics↗

bioRxiv2017

Improved Aedes aegypti mosquito reference genome assembly enables biological discovery and vector control

Female Aedes aegypti mosquitoes infect hundreds of millions of people each year with dangerous viral pathogens including dengue, yellow fever, Zika, and chikungunya. Progress in understanding the biology of this insect, and developing tools to fight it, has been slowed by the lack of a high-quality genome assembly. Here we combine diverse genome technologies to produce AaegL5, a dramatically improved and annotated assembly, and demonstrate how it accelerates mosquito science and control. We anchored the physical and cytogenetic maps, resolved the size and composition of the elusive sex-determining \"M locus\", significantly increased the known members of the glutathione-S-transferase genes important for insecticide resistance, and doubled the number of chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites. Using high-resolution QTL and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. We predict that AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly arboviral vector.

genomics↗

bioRxiv2017

orco mutagenesis causes loss of antennal lobe glomeruli and impaired social behavior in ants

Life inside ant colonies is orchestrated with a diverse set of pheromones, but it is not clear how ants perceive these social cues. It has been proposed that pheromone perception in ants evolved via expansions in the numbers of odorant receptors (ORs) and antennal lobe glomeruli. Here we generate the first mutant lines in ants by disrupting orco, a gene required for the function of all ORs. We find that orco mutants exhibit severe deficiencies in social behavior and fitness, suggesting that they are unable to perceive pheromones. Surprisingly, unlike in Drosophila melanogaster, orco mutant ants also lack most of the approximately 500 antennal lobe glomeruli found in wild-types. These results illustrate that ORs are essential for ant social organization, and raise the possibility that, similar to mammals, receptor function is required for the development and/or maintenance of the highly complex olfactory processing areas in the ant brain.

evolutionary biology↗