John M Marshall

John M Marshall
University of California, Berkeley | UCB · Division of Biostatistics

PhD

About

159
Publications
18,810
Reads
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2,733
Citations
Additional affiliations
October 2012 - December 2014
Imperial College London
Position
  • MRC Research Fellow

Publications

Publications (159)
Article
Full-text available
Building on an exercise that identified potential harms from simulated investigational releases of a population suppression gene drive for malaria vector control, a series of online workshops identified nine recommendations to advance future environmental risk assessment of gene drive applications.
Article
Mosquito-borne diseases such as malaria continue to pose a major global health burden, and the impact of currently-available interventions is stagnating. Consequently, there is interest in novel tools to control these diseases, including gene drive-modified mosquitoes. As these tools continue to be refined, decisions on whether to implement them in...
Preprint
Full-text available
Close-kin mark-recapture (CKMR) methods have recently been used to infer demographic parameters such as census population size and survival for fish of interest to fisheries and conservation. These methods have advantages over traditional mark-recapture methods as the mark is genetic, removing the need for physical marking and recapturing that may...
Article
Full-text available
A recurring target-site mutation identified in various pests and disease vectors alters the voltage gated sodium channel (vgsc) gene (often referred to as knockdown resistance or kdr) to confer resistance to commonly used insecticides, pyrethroids and DDT. The ubiquity of kdr mutations poses a major global threat to the continued use of insecticide...
Article
Full-text available
As gene drive mosquito projects advance from contained laboratory testing to semi-field testing and small-scale field trials, there is a need to assess monitoring requirements to: i) assist with the effective introduction of the gene drive system at field sites, and ii) detect unintended spread of gene drive mosquitoes beyond trial sites, or resist...
Article
Full-text available
CRISPR-based genetic engineering tools aimed to bias sex ratios, or drive effector genes into animal populations, often integrate the transgenes into autosomal chromosomes. However, in species with heterogametic sex chromsomes (e.g. XY, ZW), sex linkage of endonucleases could be beneficial to drive the expression in a sex-specific manner to produce...
Preprint
Full-text available
Gene-drive systems offer an important new avenue for spreading beneficial traits into wild populations. Their core components, Cas9 and guide RNA (gRNA), can either be linked within a single cassette (full gene drive, fGD) or provided in two separate elements (split gene drive, sGD) wherein the gRNA-bearing element drives in the presence of an inde...
Poster
Full-text available
Vector-borne diseases such as malaria continue to pose a major global health burden, accounting for over 700,000 deaths annually. Despite the success of long-lasting insecticide-treated nets (LLINs) at reducing the malaria burden, the impact of these and other currently available tools is now stagnating. Consequently, there is interest in novel vec...
Poster
Full-text available
MGDrivE (Mosquito Gene Drive Explorer) is an open-source modeling framework to simulate and evaluate novel genetic control tools in spatial mosquito populations. The software has four modules: A) a genetic inheritance module accommodates the dynamics of gene drive systems, B) a population dynamic module accounts for mosquito life history, D) a land...
Chapter
Full-text available
Deep Learning has achieved great successes in various complex tasks such as image classification, detection and natural language processing. This work describes the process of designing and implementing seven deep learning approaches to perform regressions on mosquito populations from a specific region, given co-variables such as humidity, uv-index...
Preprint
Full-text available
Background: In the Greater Mekong Subregion (GMS), engaging in forest activities is a major risk factor for malaria. As countries focus their malaria control and elimination efforts on forest-going populations, a better understanding of their mobility patterns and risk associated with specific types of forest-going trips is essential. Methods: Betw...
Preprint
Background: In the Greater Mekong Subregion (GMS), forest-going populations are considered high-risk populations for malaria and are increasingly targeted by national control programs’ elimination efforts. A better understanding of forest-going populations’ mobility patterns and risk associated with specific types of forest-going trips is necessary...
Preprint
Background In the Greater Mekong Subregion (GMS), forest-going populations are considered high-risk populations for malaria and are increasingly targeted by national control programs’ elimination efforts. A better understanding of forest-going populations’ mobility patterns and risk associated with specific types of forest-going trips is necessary...
Article
Full-text available
The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and Zika virus, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular ge...
Article
Full-text available
Background: Vector-borne diseases are a major cause of disease burden in Guayaquil, Ecuador, especially arboviruses spread by Aedes aegypti mosquitoes. Understanding which household characteristics and risk factors lead to higher Ae. aegypti densities and consequent disease risk can help inform and optimize vector control programs. Methods: Cros...
Preprint
Full-text available
A rare example of a successful long-term elimination of the mosquito Aedes aegypti is in Brisbane, Queensland, where the legislatively-enforced removal of rainwater tanks drove its disappearance by the mid-1950s. However, a decade-long drought led to the mass installation of rainwater tanks throughout the region, re-introducing critical breeding si...
Article
Full-text available
Forest-going populations are key to malaria transmission in the Greater Mekong Sub-region (GMS) and are therefore targeted for elimination efforts. Estimating the size of this population is essential for programs to assess, track and achieve their elimination goals. Leveraging data from three cross-sectional household surveys and one survey among f...
Article
Full-text available
Mosquito-borne diseases, such as dengue and malaria, pose significant global health burdens. Unfortunately, current control methods based on insecticides and environmental maintenance have fallen short of eliminating the disease burden. Scalable, deployable, genetic-based solutions are sought to reduce the transmission risk of these diseases. Patho...
Article
Full-text available
Cas9/guide RNA (gRNA)-based gene drive systems are expected to play a transformative role in malaria elimination efforts., whether through population modification, in which the drive system contains parasite-refractory genes, or population suppression, in which the drive system induces a severe fitness load resulting in population decline or extinc...
Article
Full-text available
Engineered reproductive species barriers are useful for impeding gene flow and driving desirable genes into wild populations in a reversible threshold-dependent manner. However, methods to generate synthetic barriers have not been developed in advanced eukaryotes. To overcome this challenge, we engineered SPECIES (Synthetic Postzygotic barriers Exp...
Poster
Full-text available
MGDrivE (Mosquito Gene Drive Explorer) is an open-source modeling framework to simulate and evaluate novel genetic control tools in spatial mosquito populations. The software has four modules (right): i) a genetic inheritance module accommodates the dynamics of gene drive systems, ii) a population dynamic module accounts for mosquito life history,...
Article
Full-text available
Interest in gene drive technology has continued to grow as promising new drive systems have been developed in the lab and discussions are moving towards implementing field trials. The prospect of field trials requires models that incorporate a significant degree of ecological detail, including parameters that change over time in response to environ...
Preprint
Full-text available
The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and zika, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular genetic...
Preprint
Full-text available
Forest-going populations are key to malaria transmission in the Greater Mekong Sub-region (GMS) and are therefore targeted for elimination efforts. Estimating the size of this population is essential for programs to assess, track and achieve their 2030 elimination goals. Leveraging data from three cross-sectional household surveys and one survey am...
Article
Full-text available
Background Attractive targeted sugar baits (ATSBs) are a promising new tool for malaria control as they can target outdoor-feeding mosquito populations, in contrast to current vector control tools which predominantly target indoor-feeding mosquitoes. Methods It was sought to estimate the potential impact of these new tools on Plasmodium falciparum...
Article
Full-text available
As countries in the Greater Mekong Sub-region (GMS) increasingly focus their malaria control and elimination efforts on reducing forest-related transmission, greater understanding of the relationship between deforestation and malaria incidence will be essential for programs to assess and meet their 2030 elimination goals. Leveraging village-level h...
Preprint
Full-text available
The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and zika, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular genetic...
Preprint
The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and zika, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular genetic...
Article
Full-text available
CRISPR-based gene-drive systems, which copy themselves via gene conversion mediated by the homology-directed repair (HDR) pathway, have the potential to revolutionize vector control. However, mutant alleles generated by the competing non-homologous end-joining (NHEJ) pathway, resistant to Cas9 cleavage, can interrupt the spread of gene-drive elemen...
Article
Full-text available
Homing based gene drives, engineered using CRISPR/Cas9, have been proposed to spread desirable genes throughout populations. However, invasion of such drives can be hindered by the accumulation of resistant alleles. To limit this obstacle, we engineer a confinable population modification Home-and-Rescue (HomeR) drive in Drosophila targeting an esse...
Article
Full-text available
Background Dengue fever is a mosquito-borne infectious disease that has caused major health problems. Variations in dengue virus (DENV) genes are important features of epidemic outbreaks. However, the associations of DENV genes with epidemic potential have not been extensively examined. Here, we assessed new genotype invasion of DENV-1 isolated fro...
Chapter
Full-text available
The discovery of CRISPR-based gene editing and its application to homing-based gene drive has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. At the same time, CRISPR-based gene editing has enabled a range of self-limiti...
Article
The transition of new technologies for public health from laboratory to field is accompanied by a broadening scope of engagement challenges. Recent developments of vector control strategies involving genetically engineered mosquitoes with gene drives to assist in the eradication of malaria have drawn significant attention. Notably, questions have a...
Preprint
Full-text available
After more than a century of sustained work by mathematicians, biologists, epidemiologists, probabilists, and other experts, dynamic models have become a vital tool for understanding and describing epidemics and disease transmission systems. Such models fulfill a variety of crucial roles including data integration, estimation of disease burden, for...
Article
Full-text available
Gene drive organisms (GDOs), whose genomes have been genetically engineered to spread a desired allele through a population, have the potential to transform the way societies address a wide range of daunting public health and environmental challenges. The development, testing, and release of GDOs, however, are complex and often controversial. A key...
Preprint
Full-text available
Background Vector-borne diseases are a major cause of disease burden in Guayaquil, Ecuador, especially arboviruses spread by Aedes aegypti mosquitoes. Understanding which household characteristics and risk factors lead to higher Ae. aegypti densities and consequent disease risk can help inform and optimize vector control programs. Methods Cross-se...
Poster
Full-text available
Models that simulate the effects of interventions on malaria vectors and transmission make assumptions about how mosquitoes move in the environment, such as isotropic behavior and no sex-related differences. These are applied to dispersal between households and villages and processes such as host-seeking and oviposition. Most models use mathematica...
Poster
Full-text available
CRISPR/Cas9-based technologies have revitalized interest in gene-editing technologies as means to control mosquito-borne diseases. Amongst candidate disease-control mechanisms, gene- replacement strategies are considered some of the most promising due to their resilience to generation of resistant alleles (caused by errors in homology-directed repa...
Article
Full-text available
Cas9/gRNA-mediated gene-drive systems have advanced development of genetic technologies for controlling vector-borne pathogen transmission. These technologies include population suppression approaches, genetic analogs of insecticidal techniques that reduce the number of insect vectors, and population modification (replacement/alteration) approaches...
Preprint
Full-text available
Interest in gene drive technology has continued to grow as promising new drive systems have been developed in the lab and discussions are moving towards implementing field trials. The prospect of field trials requires models that incorporate a significant degree of ecological detail, including parameters that change over time in response to environ...
Article
CRISPR-Cas9-based gene drive systems possess the inherent capacity to spread progressively throughout target populations. Here we describe two self-copying (or active) guide RNA-only genetic elements, called e-CHACRs and ERACRs. These elements use Cas9 produced in trans by a gene drive either to inactivate the cas9 transgene (e-CHACRs) or to delete...
Preprint
Full-text available
CRISPR-based gene drive systems, which copy themselves based on gene conversion mediated by the homology directed repair (HDR) pathway, have potential to revolutionize vector control. However, mutant alleles generated by the competing non-homologous end-joining (NHEJ) pathway that are rendered resistant to Cas9 cleavage can interrupt the spread of...
Presentation
Full-text available
Comparing mosquito replacement gene-drive technology against population suppression in São Tomé and Príncipe in the presence of genetic standing variation and resistant allele formation rates. https://chipdelmal.github.io/MGDrivE_Presentations/MMC2020/
Preprint
Full-text available
Homing based gene drives, engineered using CRISPR/Cas9, have been proposed to spread desirable genes into target populations. However, spread of such drives can be hindered by the accumulation of resistance alleles. To overcome this significant obstacle, we engineer a population modification Home-and-Rescue (HomeR) drive in Drosophila melanogaster...
Preprint
Full-text available
Engineered reproductive species barriers are useful for impeding gene flow and driving desirable genes into wild populations in a reversible threshold-dependent manner. However, methods to generate synthetic barriers are lacking in advanced eukaryotes. To overcome this challenge, we engineered SPECIES ( S ynthetic P ostzygotic barriers E xploiting...
Preprint
Full-text available
The development of Cas9/gRNA-mediated gene-drive systems has bolstered the advancement of genetic technologies for controlling vector-borne pathogen transmission. These include population suppression approaches, genetic analogs of insecticidal techniques that reduce the number of vector insects, and population modification (replacement/alteration)...
Article
Information about genetic engineering (GE) for vector control in the United States is disseminated primarily in English, though non-English speakers are equally, and in some geographic regions even more affected by such technologies. Non-English-speaking publics should have equal access to such information, which is especially critical when the tec...
Article
Full-text available
The discovery of CRISPR-based gene editing and its application to homing-based gene drive systems has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. Gene drive systems that display threshold-dependent behavior could pot...
Preprint
Full-text available
As countries in the Greater Mekong Sub-region (GMS) increasingly focus their malaria control and elimination efforts on forest-going populations, greater understanding of the relationship between deforestation and malaria incidence will be essential for programs to assess and meet their 2030 elimination goals. Leveraging village-level health facili...
Article
Full-text available
Mosquitoes are important vectors for pathogens that infect humans and other vertebrate animals. Some aspects of adult mosquito behavior and mosquito ecology play an important role in determining the capacity of vector populations to transmit pathogens. Here, we re-examine factors affecting the transmission of pathogens by mosquitoes using a new app...
Article
Full-text available
Mosquitoes containing gene drive systems are being developed as complementary tools to prevent transmission of malaria and other mosquito-borne diseases. As with any new tool, decision makers and other stakeholders will need to balance risks (safety) and benefits (efficacy) when considering the rationale for testing and deploying gene drive-modifie...
Article
Vector-borne diseases, such as dengue, Zika and malaria, are a major cause of morbidity and mortality worldwide. These diseases have proven difficult to control and currently available management tools are insufficient to eliminate them in many regions. Gene drives have the potential to revolutionize vector-borne disease control. This suite of tech...
Article
Full-text available
CRISPR-based gene drives can spread through wild populations by biasing their own transmission above the 50% value predicted by Mendelian inheritance. These technologies offer population-engineering solutions for combating vector-borne diseases, managing crop pests, and supporting ecosystem conservation efforts. Current technologies raise safety co...
Article
Full-text available
Aedes aegypti, the principal mosquito vector for many arboviruses that increasingly infect millions of people every year. With an escalating burden of infections and the relative failure of traditional control methods, the development of innovative control measures has become of paramount importance. The use of gene drives has sparked significant e...
Article
Full-text available
Small laboratory cage trials of non-drive and gene-drive strains of the Asian malaria vector mosquito, Anopheles stephensi, were used to investigate release ratios and other strain properties for their impact on transgene spread during simulated population modification. We evaluated the effects of transgenes on survival, male contributions to next-...
Article
Full-text available
Background: Dengue is the most prevalent mosquito-borne disease in the world, with China affected seriously in recent years. 65.8% of dengue cases identified in mainland China since 2005 were reported from the city of Guangzhou. Methods: In this study, we described the incidence rate and distribution of dengue cases using data collected form Nat...
Article
Full-text available
1.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 r...
Preprint
Full-text available
Mosquitoes are important vectors for pathogens of humans and other vertebrate animals. Some aspects of adult mosquito behavior and mosquito ecology play an important role in determining the capacity of vector populations to transmit pathogens. Here, we re-examine factors affecting the transmission of pathogens by mosquitoes using a new approach. Un...