Performing Department
Entomology, Riverside
Non Technical Summary
The possibility of addressing major biological problems related to public and environmental health by releasing transgenic organisms into the wild was first proposed decades ago and continues to be of substantial interest. However, the field of molecular biology has struggled to live up to the great potential promised by these theoretical considerations. For example, although genetic approaches have been proposed to combat diseases transmitted by mosquitos, such diseases remain a global burden and currently infect hundreds of millions of people per year, with often devastating consequences; malaria alone is responsible for nearly half a million deaths annually, mostly among children. Gene drive systems (or gene drives) possess the potential to provide revolutionary solutions to key public health and environmental issues. Most proposed engineered gene drives are based on naturally existing 'selfish' genetic elements that function by increasing in frequency with each generation even without conferring a fitness advantage upon their host, thus forcing non-Mendelian inheritance patterns. They may enable us to potentially overcome the evolutionary disadvantages of certain desirable traits and spread these traits throughout wild populations, or to suppress populations of target species altogether. This, in turn, may enable the development of novel strategies for example, to reduce or eliminate insect-borne diseases, remove invasive foreign species, and even reverse the development of resistance to insecticides and herbicides, in an economically viable and environmentally friendly manner. Gene drives could also be used to spread advantageous traits through populations far more quickly and thoroughly than natural selection, for example, to provide aid for endangered species by spreading pathogen-resistant payload genes through exposed populations. Despite the wide-ranging applicability and vast importance of gene drives, the past decades have seen only modest progress in their development. Gene drives capable of functioning in wild populations have been created in merely a handful of organisms. This is, in part, due to the difficulty of engineering the genomes of even model organisms. However, recent advancements in molecular and synthetic biology have provided broadly applicable tools capable of engineering the genomes of diverse species, which show great potential for creating a variety of engineered gene drives in diverse organisms. Therefore, our lab will focus on the development of new types gene drive systems in both mosquitoes and crop pests including Drosophila suzukii. In addition to developing gene drives, our lab will develop a paratransgenesis method that can be applied to Citrus psyllids and other insects. Furthermore, the results of the above research will be shared with other researchers through scientific publications and presentations, in order to establish collaborations with entomologists working on different types of insect pests. The project thus aims to set a good precedent for other researchers who want to apply insights of fruit fly, citrus psyllid, or mosquito research to their own work on other insects. The results of these collaborations will also be shared in detail by publications and presentations. Lastly, but most importantly, the project also aims to educate both undergraduate and graduate students at UCR about the importance and significance of integrating knowledge on various insect species. The students who will take the Cell and Molecular biology (Biology 5A) taught by the PD in addition to other entomology related courses including insect physiology/morphology. Students will also be introduced to the latest developments from fruit fly and mosquito research, and will be encouraged to read papers on studies using various insect species. In summary, the above project will produce two major types of outputs, research results and human resources, which will together fill the gap between the two research fields: insect molecular genetics and applied entomology.
Animal Health Component
75%
Research Effort Categories
Basic
50%
Applied
50%
Developmental
(N/A)
Goals / Objectives
The ultimate goal of this project is to develop innovative genetic technologies that can be used to better manage major crop pests and disease vectors. Mosquitoes are vectors for a number of devastating human diseases including Malaria, Yellow fever, Dengue, Chikungunya, and Zika, that together infect hundreds of millions humans each year, killing millions. Crop pests, such as Drosophila Suzukii and the Asain Citrus Psyllid (ACP) cause together billions dollars of damage to the agriculture industry. Our goal is to develop new genetic-based methods to control these major worldwide pests using tools inspired from molecular and synthetic biology.The goals and objectives of this project area as follows, divided by three separate categories.1. Develop a gene drive system in Aedes aegypti, the major vector for Dengue and Zika.2. Develop a gene drive system in Drosophila Suzukii that can be used to catalytically suppress wild populations. 3. Develop a paratransgenesis based approach that can be used to spread Huanglongbing (HLB) resistance into ACP populations.
Project Methods
MethodsThe project will be conducted and evaluated as described below to accomplish each objective:Objective 1 and 2: In previous work, we reported on the development of novel, synthetic selfish genetic elements known as Medea and UDMEL, able to force themselves, and any linked cargo genes, into laboratory populations of Drosophila melanogaster. However, given the difficulty of developing complex "toxins" and "antidotes" in mosquitoes, work has also been focused on developing new technologies for driving genes into populations that rely on generating and using the underdominant properties of reciprocal chromosomal translocations. In preliminary work, this concept has been extensively explored in the model organism Drosophila melanogaster, with great success (manuscript in preparation). We will therefore apply this technology to Aedes aegypti in an effort to develop a gene drive system that can spread anti-disease refractory genes throughout wild populations. For objective 2, we will be developing a toxin-antidote based system known as medea. This system can be linked with genes that can suppress a wild population of this insect.Objective 3: We are working with a strain of bacteria known as Asaia Sp. that is maternally transmitted to its offspring. We plan to first engineer this bacterium to express a fluorescent protein (GFP) to see if we can detect maternal transmission in ACP. If so, then we will then engineer the bacterium to secrete anti-HLB effectors and then challenge the ACP with HLB to see if we can confer resistance to HLB by using genetically modified bacterium. If this approach is successful, this may save citrus trees in California from being destroyed by HLB. We can also potentially apply this technique to other insects that vector plant pathogens.Objective 4: As the research develops, results will be presented in seminars, workshops and international meetings. Collaboration will be established with scientists working on different types of pest insects, to try and develop these systems in those insects.Objective 5: The PD is expected to teach an undergraduate level cell a molecular biology course (Bio 5A) starting from Spring 2016. This course can be utilized as perfect opportunity to educate students about the benefit and significance of being familiarized with latest outcomes from gene drive research. The latest results from the research part of this project, as well as those from other researches, will be actively included in the course contents and students will be encouraged to read research papers relating to gene drive and paratransgenesis in various insect pests.Evaluation: The research part of the project (Objectives 1, 2 and 3) will be evaluated based on the number and impact of research papers published. The impact of each paper will be measured based on the number of times the paper is cited by other authors. Outcomes of Objective 4 will be evaluated based on the number of seminars, workshops and meetings where the research results will be presented, as well as by the number of collaborations established with other labs. The outcomes of Objective 5 will be evaluated by exams in the class, as well as by the number of students who will apply knowledge of gene drive and paratransgeneis to their own research projects.