Completing the genetic toolkit for the control of global Tephritid pests

We aim to develop an innovative genetic control strategy to address the increasing challenges posed by insect agricultural pests, particularly Tephritid fruit flies. The proposed work is set against the backdrop of climate change, which will exacerbate the range and impact of pests as well as the increasingly unsustainable use of chemical pest control. Our target is Ceratitis capitata, the Mediterranean fruit fly, which significantly impacts agriculture globally and is predicted to arrive in the UK within 2 decades. In malaria vectors we have pioneered gene drive technology that promises to provide a powerful alternative for the area-wide control of harmful insect populations. Gene drive technology, by biassing inheritance, allows desired genetic traits to be spread through populations which can also lead to their elimination. It is an equitable-access technology that is environmentally friendly due to its species-specific mode of action. No gene drive has ever been tested in the environment, however, for medically-relevant mosquito species the technology has reached a stage where gene drives can rapidly propagate through and eliminate vector populations in the laboratory. Today, agricultural insect pests are considered the next frontier to which gene drive technology could impactfully be applied. We already made significant strides towards this goal during previous BBSRC-funded research programmes and have: Established the CRISPR genome-editing toolkit in the medfly Built and tested the first generation of homing gene drives in the medfly Demonstrated gene drives that convert medfly females into harmless XX males Identified and validated female fertility genes that could host such gene drives combining sex conversion with the sterilisation of females These advances present a unique opportunity. To date no agricultural insect pest species has been successfully eliminated under lab containment by gene drive which we are in now a position to accomplish. In the medfly the completion of gene drive technology is currently prevented by insufficient germline activity of the CRISPR genome editors. This is due to the availability of few well characterised and effective regulatory elements for transgene expression which in turn requires a better understanding of gene expression programs in the ovaries and testis of the medfly. Our aims in this project are to: Demonstrate that caged medfly populations can be eradicated in the laboratory by gene drive Gain a deeper understanding germline biology and to improve the efficiency of genome editing in the medfly Study the biology and competitiveness of sex converted males, a unique window into sexually dimorphic traits offered only by the medfly system Combine these insights to build improved suppressive gene drives for sex conversion The project is relevant to the BBSRC's long-term research and innovation priorities as it seeks to develop a sustainable alternative to chemical pesticides. By focusing on the genetic control of agricultural pests, the project aligns with the BBSRC's goals of advancing agricultural productivity and environmental sustainability. If successful, the resulting intervention could lead to significant reductions in medfly populations, decreasing crop damage and economic losses for farmers. The project's approach could offer a more cost-effective alternative to currently applied interventions and has the potential to be adapted to other Tephritid species, thereby having a broad impact on global agriculture. As an engineering biology project it also provides training opportunities in sought-after-skills for staff as well as students that form part of our team every year.