bioRxiv ScienceSearch

Biology subjects

Marshall, J. M.

Publications and source records attributed to Marshall, J. M..

4 recordsLinked to original sources

Transforming Insect Population Control with Precision Guided Sterile Males

The sterile insect technique (SIT) is an environmentally safe and proven technology to suppress wild populations. To further advance its utility, a novel CRISPR-based technology termed \"precision guided SIT\" (pgSIT) is described. PgSIT mechanistically relies on a dominant genetic technology that enables simultaneous sexing and sterilization, facilitating the release of eggs into the environment ensuring only sterile adult males emerge. Importantly, for field applications, the release of eggs will eliminate burdens of manually sexing and sterilizing males, thereby reducing overall effort and increasing scalability. To demonstrate efficacy, we systematically engineer multiple pgSIT systems in Drosophila which consistently give rise to 100% sterile males. Importantly, we demonstrate that pgSIT-generated males are fit and competitive. Using mathematical models, we predict pgSIT will induce substantially greater population suppression than can be achieved by currently-available self-limiting suppression technologies. Taken together, pgSIT offers to transform our ability to control insect agricultural pests and disease vectors.

synthetic biology

MGDrivE: A modular simulation framework for the spread of gene drives through spatially-explicit mosquito populations

Malaria, dengue, Zika, and other mosquito-borne diseases continue to pose a major global health burden through much of the world, despite the widespread distribution of insecticide-based tools and antimalarial drugs. The advent of CRISPR/Cas9-based gene editing and its demonstrated ability to streamline the development of gene drive systems has reignited interest in the application of this technology to the control of mosquitoes and the diseases they transmit. The versatility of this technology has also enabled a wide range of gene drive architectures to be realized, creating a need for their population-level and spatial dynamics to be explored. To this end, we present MGDrivE (Mosquito Gene Drive Explorer): a simulation framework designed to investigate the population dynamics of a variety of gene drive architectures and their spread through spatially-explicit mosquito populations. A key strength of the MGDrivE framework is its modularity: a) a genetic inheritance module accommodates the dynamics of gene drive systems displaying user-defined inheritance patterns, b) a population dynamic module accommodates the life history of a variety of mosquito disease vectors and insect agricultural pest species, and c) a landscape module accommodates the distribution of insect metapopulations connected by migration in space. Example MGDrivE simulations are presented to demonstrate the application of the framework to CRISPR/Cas9-based homing gene drive for: a) driving a disease-refractory gene into a population (i.e. population replacement), and b) disrupting a gene required for female fertility (i.e. population suppression), incorporating homing-resistant alleles in both cases. We compare MGDrivE with other genetic simulation packages, and conclude with a discussion of future directions in gene drive modeling.

genetics

Effects of Spatial Heterogeneity on Transmission Potential in Vectorial-Contact Networks: A Comparison of Three Aedes aegypti Control Strategies

Dengue, chikungunya and zika are all transmitted by the Aedes aegypti mosquito. Despite the strong influence of host spatial distribution and movement patterns on the ability of mosquito vectors to transmit pathogens, there is little understanding how these complex interactions modify the spread of disease in spatially heterogeneous populations. In light of present fears of a worldwide zika epidemic, and failures to eradicate dengue and chikungunya; there is a pressing need to get a better picture of how high-resolution details such as human movement in a small landscape, modify the patterns of transmission of these diseases and how different mosquito-control interventions could be affected by these movements.\n\nIn this work we use a computational agent-based model (ABM) to simulate mosquito-human interactions in two different levels of spatial heterogeneity, with human movement, and in the presence of three mosquito-control interventions (spatial spraying, the release of Wolbachia-infected mosquitoes and release of insects with dominant lethal gene). To analyse the results from each of these experiments we examined mosquito population dynamics and host to host contact networks that emerged from the distribution of consecutive bites across humans. We then compared results across experiments to understand the differential effectiveness of different interventions in both the presence and absence of spatial heterogeneities, and analysed network measures of epidemiological relevance (degree probability distributions, mean path length, network density and small-worldness).\n\nFrom our experiments we conclude that spatial heterogeneity greatly influences how a pathogen may spread in a host population when mediated by a mosquito vector, and that these important heterogeneities also strongly affect effectiveness of interventions. Finally, we demonstrate that these host to host vectorial-contact networks can provide operationally important information to inform selection of optimal vector-control strategies.\n\nAuthor SummaryMosquito-borne diseases transmission patterns arise from the complex interactions between hosts and vector. Because these interactions are influenced by host and vector behaviour, spatial constraints, and other factors they are amongst the most difficult to understand. In this work, we use our computational agent-based model: SoNA3BS; to simulate two spatially different settings in the presence and absence of three different mosquito-control interventions: fogging, the release of Wolbachia-infected mosquitoes and the release of insects with dominant lethal gene. Throughout these simulations, we record mosquito population dynamics and mosquito bites on persons. We then compare mosquito population dynamics to the vectorial-contact networks (that emerge from subsequent mosquito bites between humans) and, after performing these comparisons, we proceeded to show that even when mosquito population sizes are almost equal in both spatial settings, the resulting vectorial-contact networks are radically different. This has profound implications in our understanding of how mosquito-borne diseases spread in human populations and is relevant to the effective use of resources allocated to stop these pathogens from causing more harm in human populations.

bioinformatics

Engineered reciprocal chromosome translocations drive high threshold, reversible population replacement in Drosophila

Replacement of wild insect populations with transgene-bearing individuals unable to transmit disease or survive under specific environmental conditions provides self-perpetuating methods of disease prevention and population suppression, respectively. Gene drive mechanisms that require the gene drive element and linked cargo exceed a high threshold frequency to spread are attractive because they offer several points of control: they bring about local, but not global population replacement; and transgenes can be eliminated by reintroducing wildtypes into the population so as to drive the frequency of transgenes below the threshold required for drive. It has long been recognized that reciprocal chromosome translocations could, in principal, be used to bring about high threshold gene drive through a form of underdominance. However, translocations able to drive population replacement have not been reported, leaving it unclear if translocation-bearing strains fit enough to mediate gene drive can easily be generated. Here we use modeling to identify a range of conditions under which translocations should spread, and the equilibrium frequencies achieved, given specific introduction frequencies, fitness costs and migration rates. We also report the creation of engineered translocation-bearing strains of Drosophila melanogaster, generated through targeted chromosomal breakage and homologous recombination. By several measures translocation-bearing strains are fit, and drive high threshold, reversible population replacement in laboratory populations. These observations, together with the generality of the tools used to generate translocations, suggest that engineered translocations may be useful for controlled population replacement in many species.

evolutionary biology