13TSB_TIBio: Genomes and synthetic biology for development of novel pest control technologies

Oxitec is the world leader in application of synthetic biology to control of pest insects. Oxitec's RIDL(R) technology relies on release of mass-reared genetically sterile (transgenic) male insects that mate with their wild pest counterparts, thereby causing a drop in population. RIDL efficacy is proven against Ae. aegypti, reducing wild populations in the Caribbean and Brazil by 80-96%. A costly aspect of current technology is the means of selecting males only for release, important as the females blood-feed and transmit disease. This project aims to develop a novel method of producing male-only cohorts of RIDL mosquitoes ('genetic sexing') that would both markedly reduce costs and cement Oxitec's leadership in the field. Next-generation sequencing datasets will be analysed to help develop new RIDL traits in Ae. aegypti mosquitoes, to increase the efficiency of applying our technology in the field. Development of targeted bioinformatics methodology, and successful engineering of a novel genetic sexing technique, will provide a pipeline for development of new RIDL traits in other pests important for public health and agriculture.

Oxitec is the world leader in application of synthetic biology to control of pest insects. Oxitec's RIDL technology relies on release of mass-reared genetically sterile (transgenic) male insects that mate with their wild pest counterparts, thereby causing a drop in population. RIDL efficacy is proven against the denuge mosquito, Ae. aegypti, reducing wild populations in Brazil by ca. 96%. A costly aspect of current technology is the means of selecting males only for release, important as the females blood-feed and transmit disease. This project aims to develop a novel method of producing male-only cohorts of RIDL mosquitoes ('genetic sexing') that would both markedly reduce costs and cement Oxitec's leadership in the field. Next-generation sequencing datasets will be analysed to help develop new RIDL traits in Ae. aegypti mosquitoes, to increase the efficiency of applying our technology in the field. Development of targeted bioinformatics methodology, and successful engineering of a novel genetic sexing technique, will provide a pipeline for development of new RIDL traits in other pests important for public health and agriculture.

Dengue fever is not always fatal, but it is a painful and debilitating disease with no effective cure. It is spread by the Aedes aegypti mosquito, which is present in many tropical countries. Globally, approximately 2.5 billion people are at risk of contracting dengue fever. 6% of sufferers go on to contract the more serious form of dengue, known as dengue haemorrhagic fever, which can progress into a critical condition called dengue shock syndrome. In 2.5% of cases, these severe conditions can prove fatal.

Since the 1970s the virus has spread dramatically. At that time only nine countries experienced epidemics; the figure today is more than one hundred, with many of these countries having no prior history of the disease. Globally, 75% of the burden of dengue fever is concentrated in South-East Asia, Latin America, the Caribbean and the Western Pacific Region, but it is found in most tropical areas. Aedes aegypti, the mosquito that transmits dengue (known as the disease 'vector') is also found in 28 states of the USA, putting much of the country at risk of dengue epidemics. The disease is primarily concentrated in urban areas as the Aedes aegypti mosquito is a predominantly urban species. Consequently, it can affect countries at every level of the socio-economic spectrum. With the progression of climate change and the globalisation of travel and trade it is predicted that dengue fever may spread further outside the current tropical zones due to the potential extension in the habitat of its vector.

Due to the speed of its spread, its increasingly serious complications, and the overwhelming burden of illness and death it causes, many consider dengue the world's most important insect-transmitted viral disease.

This project will provide new information that will be of value to policy makers, health care professionals and applied entomologist interested in controlling Dengue and Ae. aegypti. Therefore this project has the potential to decease the burden of Dengue in effected countries.