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Khamis, D.

Publications and source records attributed to Khamis, D..

2 recordsLinked to original sources

The effect of dispersal and preferential mating on the genetic control of mosquitoes

Mosquito-borne diseases cause significant social and economic damage across much of the globe. New biotechnologies that utilise manipulations of the mosquito genome have been developed to combat disease. The successful implementation of genetic mosquito control technologies may depend upon ecological, evolutionary and environmental factors, as well as the specifications of the chosen technology. Understanding the influence of these external factors will help inform how best to deploy a chosen technology to control vectors of infectious diseases. We use a continuous-time stochastic spatial network model of a mosquito life-cycle coupled to population genetics models to investigate the impact of releasing seven types of genetic control technology: a self-limiting lethal gene, two underdominance threshold gene drives, two homing gene drives and two Wolbachia systems. We apply the mathematical framework to understand control interventions of two archetypes of mosquito species: a short-range dispersing Aedes aegypti and comparatively longer-range dispersing Anopheles gambiae. We show that mosquito dispersal behaviour is an extremely important factor in determining the outcome of a release programme. Assortative mating - where the mating success of genetically modified males is lower than their wild counterparts - can facilitate the spatial containment of gene drives. The rapid evolution of strong mating preference can damage the efficacy of control efforts for all control technologies. We suggest that there cannot be a one-size-fits-all approach to regulation and implementation of vector control; there must be application-specific control plans that take account of understudied ecological, evolutionary and environmental factors.

ecology

Heterogeneity in clone dynamics within and adjacent to intestinal tumours identified by Dre-mediated lineage tracing

Somatic models of tissue pathology commonly utilise induction of gene specific mutations in mice mediated by spatiotemporal regulation of Cre recombinase. Subsequent investigation of the onset and development of disease can be limited by the inability to track changing cellular behaviours over time. Here a lineage tracing approach based on ligand dependent activation of Dre recombinase that can be employed independently of Cre is described. The clonal biology of intestinal epithelium following Cre-mediated stabilisation of {beta}-catenin reveals that within tumours many new clones rapidly become extinct. Surviving clones show accelerated population of tumour glands compared to normal intestinal crypts but in a non-uniform manner indicating that intra-tumour glands follow heterogeneous dynamics. In tumour adjacent epithelium clone sizes are smaller than in the background epithelium as a whole. This suggests a zone of around 5 crypt diameters within which clone expansion is inhibited by tumours and that may facilitate their growth.

cancer biology