Progress 11/01/09 to 10/31/14
Outputs
Target Audience: In order to explain why Wolbachia can induce cytoplasmic incompatibility (CI) and how this can be used for dengue control, we invited people working on vector-borne disease control, including those working in CDC and pest control organization, to a workshop and give a presentation to them. We also replied the questions addressed by them. This discussion greatly help to reslove their concern on biosafty related to Wolbachia-based mosquito control. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided? This project led to training of a number of public health people working on vector control in China. The training included how to better work on mosquito surveillance in the field using ovitrap and adult trap and how to work on community education on a novel vector control strategy. In addition, this project also providesd opportunities for graduate students and post-doc to study the molecular interaction between host and microbe through the modern functional and bioinformatics assay. How have the results been disseminated to communities of interest? We had several meetings with the community to explain how Wolbachia-mediated cytoplasmic incompatibility could be used to control the primary dengue vector Aedes albopictus population in China. We also used the newspaper and internet to deliver the information to a broader audience. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
This project generated a number of novel knowledge that aids in understanding of the mechanism underlying cytoplasmic incompatibility, which can facilitate development of a better strategy to use Wolbachia for mosquito borne disease control, in particular dengue and malaria. Below is summary for each aim: 1). Construct an in silico Wolbachia-mosquito protein interactions network. Major activities haven been completed and results will be submitted for publication. Wolbachia-mosquito protein interactions network was constructed succeefully to explore the interaction between Wolbachia and mosquito host. 2). Define the response of mosquito genes in reproductive tissues to Wolbachia infection. Major activities have been completed and data were collected. We identified the genes regulated by Wolbachia in mosquito female ovaries and male testis. 3). Identify host factors that determine CI expression. The data were collected and some potential CI candidates need to be further functionally characterized.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2014
Citation:
Joshi, D., McFadden, M. J., Bevins, D., Zhang, F. & Xi, Z. (2014). Wolbachia strain wAlbB confers both fitness costs and benefit on Anopheles stephensi. Parasites & Vectors. 7:336-444.
Bourtzis, K., Dobson, S. L., Xi, Z. Rasgon, J. L. Calvitti, M., Moreira, L. A., Bossin, H. C., Moretti, R., Baton, L. A., Hughes, G. L., Mavingui, P., & Gilles, J. (2014). Harnessing mosquitoWolbachia symbiosis for vector and disease control. Acta Tropica. 132 Suppl: S150-63. doi: 10.1016
Pan, X., Liu, Q., & Xi, Z. Advance in Developing Wolbachia as a Mean to Control Mosquito and Mosquito-borne Diseases. Chinese Journal of Vector Biology and Control. Vol.25, No.1, 1-7
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Progress 01/01/13 to 09/30/13
Outputs
Target Audience: The target audience includes scientists, government officials, funding agents, community residents and students. Changes/Problems: Due to lack of a known gene determining cytoplasmic incompatibility as a positive control, the functional assay (through RNAi-mediated gene silencing) becomes difficult to be carried out. After failing for many times, we are now switching to the other assays, e.g., microRNAi and chemical treatment. What opportunities for training and professional development has the project provided? We have been invited to introduce our work in two international and two workshops during this period. These conferences includes: (1) Develop Wolbachia as an agent for malaria vector control. August 1st, 2013. Fifth International Symposium of Parasitology/14th Biennial Meeting of the Chinese Society of Parasitology. Guiyang, Guizhou, China. (2) Wolbachia-mediated pathogen interference and cytoplasmic incompatibility in mosquitoes and its use in vector-borne disease control. May 31st, 2013. The Fourth Conference on Computational and Mathematical. The workshop includes: (1) Wolbachia Invades Anopheles stephensi Population and Induces Refractoriness to Plasmodium Infection. July 15-19, 2013. The 6th EMBO Workshop on Molecular and Population Biology of Mosquitoes and Other Disease Vectors: From Basic Vector Biology to Disease Control. Kolymbari, Greece; (2) Wolbachia-based dengue control: targets to the secondary vector Aedes albopictus. International Workshop on Aedes albopictus, the Asian tiger mosquito. March 22rd, 2013. Pavia, Italy. We also gave two seminars in college/university: (1) Interaction of a Symbiotic bacterium with Human Pathogens in Mosquitoes and its Implementation in Disease Control. Andrews University. August 27th, 2013. Berrien Springs, Michigan; (2) Wolbachia-mosquito hosts interactions and it use in vector-borne disease control. May 23rd. Nanjing Agriculture University, Nanjing, China. In addition, this project has brought training opportunity for four postdocs: Drs. Guowu Bian, Deepak Joshi, Xiaoling Pan and Yu Wu, one master student Ryan Shawna, and two undergraduate students, Mike Mcfadden and David Bevins. How have the results been disseminated to communities of interest? We utilized a number of media as mentioned in the above to disseminate the generated novel knowledge into community. For the field trial project in China, we hired two staff in charge of community education. By working together with official in local Central of Disease Control and Prevention, we introduced to the community how Wolbachia-mediated cytoplasmic incompatibility can be used to control mosquito-borne diseases. We also provided information about safety of the technology in relation to the traditional control strategies. In the meanwhile, we are developing a web site to introduce this new concept. What do you plan to do during the next reporting period to accomplish the goals? We will improve our Wolbachia-infected mosquito system for disease control. For example, we will perfect the system by increasing the efficacy of pathogen block and reducing the Wolbachia-associated fitness cost. We will better understand the cytoplasmic incompatibility such that it can better serve for disease control. In addition, we will continue working until regulation approval is accomplished by the China Ministry of Agriculture.
Impacts
What was accomplished under these goals?
With establishment of Wolbachia into malaria mosquito vector and demonstration of its ability to induce cytoplasmic incompatibility, we reported this result to the funding agents of Foundation of NIH in global health and received an invitation to submit a proposal to them. After our work was published in Science, we received inquiry from the 1st Special Forces Group (Airborne)to test Wolbachia-based malaria control in the field. A number of media, including BBC, national public radio, wired magazine, Voice of America and Mosquito Control Magazine, also contacted us and reported our work. In addition, we held three meeting in China during this period with Ministry of Agriculture to get regulation approval to use Wolbachia as a microbial pesticide fordengue control in the field.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2013
Citation:
Bian, G., Joshi, D., Dong, Y., Lu, P., Zhou, G., Xu, Y., Dimopoulos, G. & Xi, Z. (2013). Wolbachia Invades Anopheles stephensi Populations and Induces Refractoriness to Plasmodium Infection. Science. 340, 748-751.
Bian, G., Zhou, G., Lu, P. & Xi, Z. (2013). Replacing a Native Wolbachia with a Novel Strain Results in an Increase in Endosymbiont Load and Resistance to Dengue Virus in a Mosquito Vector. PLOS Neglected Tropical Diseases 7 (6): e2250.
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Progress 01/01/12 to 12/31/12
Outputs
OUTPUTS: I have attended a number of conferences to report how Wolbachia interacts with mosquito host and how Wolbachia-mediated cytoplasmic incompatibility can be used for mosquito-borne disease control. This includes: (1) giving a talk at the 61th annual meeting of America Society of Tropical Medicine and Hygiene (Nov. 11-14, 2012), (2) giving two talks at the 24th International Congress of Entomology in South Korea (August 19-24, 2012), (3) serving as chair as one section and giving one talk at the fourth International Forum for Sustainable Management of Disease Vectors in China (Nov 25-28, 2012). In addition, I was also invited to give a seminar talk about our research in the following universities and institute: University of Texas Medical Branch at Galveston, University of California at Riverside, South China Agricultural University, Guangdong Department of Science and Technology (China), International Atomic Energy Agency, Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture Insect Pest Control Laboratory (Austria). To better introduce Wolbachia-based dengue control strategy, we invited a delegation from Guangdong Department of Science and Technology to visit our field sites in Australia. In order to better deploy this novel approach for dengue control, we recruited three staff in Sun Yat-sen University-Michigan State University Joint Center of Vector Control for Tropical Diseases. We also provided training to our field trial team: Vector Control program at Guangzhou Center for Disease Control and Prevention. PARTICIPANTS: Three postdocs have worked on this project. Dr. Xiang Guo worked on prediction of Wolbachia and host proteins that involve in induction of CI. Dr. Deepak Joshi and Dr. Fengrui Zhang are working on functional characterization of those predicted CI gene candidates using RNA interference and cross experiment. One undergraduate student is working as a research assistant for the above work. TARGET AUDIENCES: We targeted audiences as follows: government official in charge of vector bored disease control, such as personnel in the local department of health and CDC, and students interested in future career on vector-born disease. Formal classroom instruction, laboratory instruction, newspaper, TV media, workshops and seminar are used to target those audiences. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Due to successful introduction of Wolbachia into Anopheles mosquitoes, we now open the possibility to use Wolbachia for malaria control. By collaboration with scientists in malaria transmission area, we are currently developing Wolbachia-induced CI as a novel malaria intervention strategy. Together with our colleagues, we demonstrated Wolbachia can be used to control mosquito-transmitted dengue fever. This has been well-accepted by scientific community. Moreover, a number of government and private funding now starts to invest into efforts to develop Wolbachia to control mosquito-borne diseases in their own countries, including China, Vietnam and Indonesia. With a success in the field trial, it is highly likely Wolbachia-induced CI will be included as novel tools for future control of vector-borne diseases by governments in a number of countries. In addition, we were also requested to develop Wolbachia as bio-pesticides for control agriculture pests in China.
Publications
- Lu, P., Bian, G., Pan, X. & Xi. Z. (2012). Wolbachia Induces Density-dependent Inhibition to Dengue Virus in Mosquito Cells. PLoS Neglected Tropical Diseases. 6(7):e1754.
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Progress 01/01/11 to 12/31/11
Outputs
OUTPUTS: We have been invited to introduce our work in two international and one national conferences in 2011. These conferences includes: (1) the 5th workshop on Molecular and population biology of diseases vectors in Kolymbari, Greece (July 14-30, 2011); (2) the 4th international symposium of parasitology in Nanning, China (Nov 5-9, 2011); (3) the 60th annual meeting of America Society of Tropical Medicine and Hygiene (Dec 4-8, 2011). In addition, we also gave seminar talk in Guangzhou University in China in July, 2011 to introduce how Wolbachia induce cytoplasmic incompatibility (CI) in mosquito. In March and May, we gave talk about our research in the annual meeting of two Gates-foundations funded projects. One was in Louisville, Kentucky while the other was in Brisbane, Australia. The goal of both meeting are to promote the understanding of CI and use of CI for vector-borne diseases control. We also presented our research to the community that may take advantage of this novel knowledge for mosquito control. By inviting our collaborators in Australia to visit our joint laboratory in China, we successfully introduced Wolbachia-based CI to publics in Guangzhou through a number of local medium reports. Finally, we also presented Wolbachia-induced CI to government in China in order to get the future support for our research. Guangdong Department of Science and Technology has become well-supportive to our research after they learnt the significance of our work. Guangzhou Center of Disease Control starts to work together on a research project to use Wolbachia-based CI for dengue control. PARTICIPANTS: Two postdocs are currently working on this project. Dr. Xiang Guo is working on prediction of Wolbachia and host proteins that involve in induction of CI. Dr. Deepak Joshi is working on functional characterization of those predicted CI gene candidates. One undergraduate student is working as a research assistant for the above work.In additon, we currently collaborate with Dr. Suzanne Thiem in MSU for discovery of CI genes. TARGET AUDIENCES: Target Audiences include agencies in charge of vector bored disease control, such as personnel in the local department of health and CDC, and students interested in future career on vector-born disease. Formal classroom instruction, laboratory instruction and workshops are used to target those audiences. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
Due to successful introduction of Wolbachia into Anopheles mosquitoes, we now open the possibility to use Wolbachia for malaria control. By collaboration with scientists in malaria transmission area, we are currently developing Wolbachia-induced CI as a novel malaria intervention strategy. Together with our colleagues, we demonstrated Wolbachia can be used to control mosquito-transmitted dengue fever. This has been well-accepted by scientific community. Moreover, a number of government and private funding now starts to invest into efforts to develop Wolbachia to control mosquito-borne diseases in their own countries, including China, Vietnam and Indonesia. With a success in the field trial, it is highly likely Wolbachia-induced CI will be included as novel tools for future control of vector-borne diseases by governments in a number of countries. In addition, we were also requested to develop Wolbachia as bio-pesticides for control agriculture pests in China.
Publications
- Pan, X., Zhou, G., Wu, J., Bian, G., Lu, P., Raikhel, A. S., Xi, Z. (2011). Wolbachia induces ROS-dependent activation of the Toll pathway to control dengue virus in the mosquito Aedes aegypti. Proceedings of the National Academy of Sciences. doi/10.1073.1116932108. Zou, Z., Souza-Neto, J. A., Xi, Z., Kokoza, V., Shin, S. W., Dimopoulos, G., Raikhel, A. S.(2011). Transcriptome analysis of Aedes aegypti transgenic mosquitoes with altered immunity. Plos Pathogens. 7(11):e1002394.
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Progress 01/01/10 to 12/31/10
Outputs
OUTPUTS: Below are major outcomes during the current budget year: 1). Wolbachia-mosquito protein-interaction network has been successfully constructed. First, we incorporated additional data from the five other species, including human and Campylobacter jejuni, and applied a domain-based approach to expand the mosquito interaction network we developed recently. Second, we used 1,386 coding sequences from Wolbachia (wPip) that naturally infect Culex mosquito to create Wolbachia-mosquito protein-interaction network through interolog- and domain-based prediction. This results in identification of 1,863 interactions between 1,225 Ae. aegypti and 320 Wolbachia proteins. Further analysis identified 49 putative mosquito pathways that interact with Wolbachia, including pathways involved in mosquito metabolism, immunity and reproduction. By integration of the protein network and microarray (see below) data, we observed important interactions between Wolbachia protein and mosquito cell cycle regulator and heat shock proteins. Evidence has supported that Wolbachia induce cytoplasmic incompatibility (CI) thorough manipulating host cell cycle. 2). We have generated Wolbachia-induced transcriptional profile in mosquito testes or ovaries with the goal to define the response of mosquito genes in reproductive tissues to Wolbachia infection. Specifically, we used microarray to compare the gene expression in testes and ovaries, related to sperm "modification" and "rescue", respectively, in Wolbachia-infected and uninfected mosquitoes. Total RNA were extracted from one-day-old virgin male testes and female ovaries, and microarray assay were conducted to analysis Wolbachia-regulated transcriptomic profile in these two tissues. As a result, 294 and 237 genes were up-regulated and 130 and 344 genes were down-regulated by Wolbachia in mosquito ovaries and testes, respectively. Functional classification of the differential expressed genes highlighted that immunity and redox are the major function groups that are targeted by Wolbachia. By clustering the above differentially expressed genes with the genes regulated by Wolbachia in midgut and carcass (from our previous studies), we further indentified common gene regulation patterns by Wolbachia across different tissues and the tissue specific regulation patterns. As expected, we observed regulation of four angiotensin converting enzyme (Ance) genes in the sex-specific manner: up-regulated in female and down-regulated or no change in the male. 3). We has started a number of CI crosses to functionally characterize host factors that can determine CI expression. The first gene we were working on is the Ance gene which shows conserved regulation pattern by Wolbachia across different insect species. We made its double strand RNA to knockdown its expression in the Waco (Wolbachia-uninfected) male to mimic the sperm modification and in the WB1 (Wolbachia-infected) female to compromise its rescue mechanism. PARTICIPANTS: This project has brought training opportunity for three postdocs: Drs. Xiang Guo, Deepak Joshi and Xiaoling Pan, and one master student: Andrew Pike. Specifically, Dr. Pan and Andrew Pike worked on microarray analysis of Wolbachia-regulated reproductive genes. Dr. Guo worked on Wolbachia-mosquito protein interaction network. Dr. Joshi worked on functionally characterize the CI genes candidates. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
The progress we made in the above initiates the study of the CI mechanisms at the systems biological and functional genomic level. The finds in both specific aim 1 and 2 are providing us a number of new insights into CI mechanism. For example, how the redox genes play roles in CI induction and how cell cycle regulators are targeted by Wolbachia. Further understanding these biological processes will provide us a number of new directions to utilize Wolbachia for control of mosquito borne disease. For example, our evidence implies that there are some common mechanisms underlying Wolbachia-mediated CI and resistance to pathogens. This will improve the Wolbachia-based transgene driver system to spread genes capable of blocking the transmission of mosquito-borne pathogens. In addition, our microarray results indicate that there is commonality on interactions of Wolbachia and rickettsia (pathogenic bacteria closely related to Wolbachia) with their hosts. For example, both of them can activate the NF-kB pathway and induce the oxidative stress in host. Thus, our studies may lead to discovery of common mechanisms that are used by these intracellular bacteria to maintain their persistent infection within host cells.
Publications
- Guo, X., Xu, Y., Bian, G., Pike, A., Xie, Y. & Xi, Z. (2010). Response of mosquito protein interaction network to the dengue infection. BMC Genomics. 11(1):380
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