Biology subjects

Antoshechkin, I.

Publications and source records attributed to Antoshechkin, I..

3 recordsLinked to original sources

bioRxiv2018

Engineered resistance to Zika virus in transgenic Ae. aegypti expressing a polycistronic cluster of synthetic miRNAs

Recent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or vectoring competency, and gene drive based methods. Here, we describe the development of mosquitoes synthetically engineered to impede vector competence to ZIKV. We demonstrate that a polycistronic cluster of engineered microRNAs (miRNAs) targeting ZIKV is expressed and fully processed following a blood meal in Ae. aegypti, ensuring the formation of mature synthetic miRNAs in the midgut where ZIKV resides in the early stages of infection. Critically, we demonstrate that engineered Ae. aegypti mosquitoes harboring the anti-ZIKV transgene have significantly reduced viral infection, dissemination, and transmission rates of ZIKV. Taken together, these compelling results provide a promising path forward for development of effective genetic-based ZIKV control strategies, which could potentially be extended to curtail other arboviruses.\n\nOne Sentence SummaryHere we describe the generation of Ae. aegypti mosquitoes that are engineered to confer reduced vector competence to Zika virus (ZIKV) and we discuss how such engineering approach can be used to combat the major health burden of ZIKV and potentially other arboviruses in the future.

synthetic biology↗

bioRxiv2017

Improved Aedes aegypti mosquito reference genome assembly enables biological discovery and vector control

Female Aedes aegypti mosquitoes infect hundreds of millions of people each year with dangerous viral pathogens including dengue, yellow fever, Zika, and chikungunya. Progress in understanding the biology of this insect, and developing tools to fight it, has been slowed by the lack of a high-quality genome assembly. Here we combine diverse genome technologies to produce AaegL5, a dramatically improved and annotated assembly, and demonstrate how it accelerates mosquito science and control. We anchored the physical and cytogenetic maps, resolved the size and composition of the elusive sex-determining \"M locus\", significantly increased the known members of the glutathione-S-transferase genes important for insecticide resistance, and doubled the number of chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites. Using high-resolution QTL and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. We predict that AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly arboviral vector.

genomics↗

bioRxiv2016

Transcriptomic Description of an Endogenous Female State in C. elegans

Understanding genome and gene function in a whole organism requires us to fully understand the life cycle and the physiology of the organism in question. Although it is traditionally though of as a hermaphrodite, C. elegans XX animals become (endogenous) females after 3 days of egg-laying. The molecular physiology of this state has not been studied as intensely as other parts of the life cycle, in spite of documented changes in behavior and metabolism that occur at this stage. To study the female state of C. elegans, we designed an experiment to measure the transcriptome of 1st day adult females, endogenous, 6th day adult females, as well as mutant feminized worms that never go through a hermaphrodite stage at these time points. Using this experimental design, we were able to measure the effects of biological aging from the transition into the female state. We find that spermless young adult animals partially phenocopy 6 day old wild-type animals that have depleted their sperm after egg-laying, and that spermless animals also exhibit fewer transcriptomic changes associated with aging throughout these 6 days. Our results indicate that sperm loss is responsible for some of the naturally occuring transcriptomic changes that occur during the life cycle of these animals. These changes involve a variety of factors, and they are enriched in transcription factors canonically associated with neuronal development and differentiation. Our data provide a high-quality picture of the changes that happen in global gene expression throughout the period of early aging in the worm.

genetics↗