Jared Bennett

University of California, Berkeley | UCB · Biophysics Graduate Group

Objective The MGDrivE (MGDrivE 1 and MGDrivE 2) modeling framework provides a flexible and expansive environment for testing the efficacy of novel gene-drive constructs for the control of mosquito-borne diseases. However, the existing model framework did not previously support several features necessary to simulate some types of intervention strate...

In response to the COVID-19 pandemic and the potential threat of future epidemics caused by novel viruses, we developed a flexible framework for modeling disease intervention effects. This tool is intended to aid decision makers at multiple levels as they compare possible responses to emerging epidemiological threats for optimal control and reducti...

Agent-based models (ABMs) simulate the formation and evolution of social processes at a fundamental level by decoupling agent behavior from global observations. In the case where ABM networks evolve over time as a result of (or in conjunction with) agent states, there is a need for understanding the relationship between the dynamic processes and ne...

Genetic control of insect populations, such as reducing the impact of mosquito-vectored diseases, became reality with the advent of CRISPR/Cas9 gene editing techniques. Since then, the field has exploded in complexity, as researchers and regulators demand ever-more realistic simulations to predict the ecological and epidemiological impact of novel...

The core components of CRISPR-based gene drives, Cas9 and guide RNA (gRNA), either can be linked within a self-contained single cassette (full gene-drive, fGD) or be provided in two separate elements (split gene-drive, sGD), the latter offering greater control options. We previously engineered split systems that could be converted genetically into...

Humans learn from the occurrence of events at different places and times to predict similar trajectories of events. We define loosely decoupled time (LDT) phenomena as two or more events that could occur in different places and across different timelines but share similarities in the nature of the event and the properties of the location. In this w...

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...

Humans learn from the occurrence of events in a different place and time to predict similar trajectories of events. We define Loosely Decoupled Timeseries (LDT) phenomena as two or more events that could happen in different places and across different timelines but share similarities in the nature of the event and the properties of the location. In...

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...

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...

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...

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...

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...

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...

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...

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,...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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)...

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...

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...

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...

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-...

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 reig...

CRISPR-based gene drives spread through populations bypassing the dictates of Mendelian genetics, offering a population-engineering tool for tackling vector-borne diseases, managing crop pests, and helping island conservation efforts; unfortunately, current technologies raise safety concerns for unintended gene propagation. Herein, we address this...

Aedes aegypti , the principal mosquito vector for many arboviruses that causes yellow fever, dengue, Zika, and chikungunya, increasingly infects 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 import...

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...

In this work, we present our framework with applications to various novel gene-drive systems such as: reciprocal chromosomal translocations, toxin-antidote-based underdominant systems. In doing so, we show how our model can be used to answer relevant questions in the field of mosquito-borne diseases elimination, such as: how to make fair comparison...

Malaria, dengue, Zika, and other mosquito-borne diseases continue to pose a major global health burden through much of the world. 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...

In this work, we present MGDrivE with example applications to threshold-dependent drives (reciprocal chromosomal translocations and toxin-antidote-based underdominant systems). We show how the timing of the releases can be optimized for the drives to fixate in the population with a minimum cost, and how this information can be applied to simulate r...

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 rei...

Mosquito-borne diseases, such as dengue, Zika, chikungunya, and yellow fever, pose significant health problems in tropical regions of the world. Control of the main vector for these diseases, the Aedes aegypti mosquito, remains elusive despite extensive efforts using traditional vector control interventions. Recent development in gene-drive technol...

Our goal for each of these species is to use mathematical models to determine optimal CRISPR-Cas9-based gene drive architectures that could be successful in controlling their agricultural impact while ensuring biosafety through the ability to remediate them from the environment in the event of negative consequences or a change in public opinion.

Traditional methods of mosquito control, while effective, are not sufficient to eliminate malaria from highly-endemic regions. Additionally, the lack of general vaccine for dengue increases the need for alternative control measures. CRISPR/Cas based gene drives provide an efficient means of genome modi ca on and potential mosquito control mechanism...

Recent developments of CRISPR-Cas9 based homing endonuclease gene drive systems for the suppression or replacement of mosquito populations have generated much interest in their use for control of mosquito-borne diseases (such as dengue, malaria, chikungunya and Zika). This is because genetic control of pathogen transmission may complement or even s...

Mismatched nucleotides arise from polymerase misincorporation errors, recombination between heteroallelic parents and chemical or physical DNA damage. Highly conserved MutS (MSH) and MutL (MLH/PMS) homologues initiate mismatch repair and, in higher eukaryotes, act as DNA damage sensors that can trigger apoptosis. Defects in human mismatch repair ge...

Fluorophore labeling of proteins while preserving native functions is essential for bulk Förster resonance energy transfer (FRET) interaction and single molecule imaging analysis. Here we describe a versatile, efficient, specific, irreversible, gentle and low-cost method for labeling proteins with fluorophores that appears substantially more robust...