Characterising novel insecticide transport to maximise efficiency and minimize environmental impact

Lead Research Organisation: Imperial College London
Department Name: Chemistry

Abstract

One of the greatest global priorities is finding strategies that will support the supply of high quality, nutritious food for the worlds fast-growing population. One vital strand that will support this is the development of novel efficient, safe insecticides with low environmental impact.
The development of insecticides has been highly successful at targeting specific active protein sites, however there are a host of physical and molecular barriers between the application site and active site of insecticide molecules. There is currently a lack of understanding of the interactions that take place between the active molecules and these biological barriers and indeed, the efficiency of transport through these barriers is not simply based on the active insecticide its self, but depends strongly on the applied formulation and its physical state.
While there has been progress in both modeling and machine learning approaches to predicting the transport and efficacy of insecticides, these approaches are also severely hampered by lack of input characterization data relating to membrane transport.
In this project we aim to develop a modular, lab based, milli-fluidic measurement platform that will allow rapid characterisation the transport of insecticides across serial model membranes and in-vitro physical barriers. This data will allow direct rapid screening and prediction of efficiency of candidate molecules, and optimisation of formulation, and we will feed into machine learning approaches that will allow us to predict membrane transport based on molecular structure. The approaches employed here will be aligned with those used within BASF and so will feed directly into their supervised and unsupervised predictive models to significantly enhance the efficiency and targeting of insecticide discovery and development. By significantly expanding the developmental parameter space beyond target site identification and interactions, we anticipate that, in the future this will lead to development of insecticide formulations with lower applied concentrations, increased specificity and improved environmental performance.

Planned Impact

Addressing UK skills demand: The most important impact of the CDT will be to train a new generation of Chemical Biology PhD graduates (~80) to be future leaders of enterprise, molecular technology innovation and translation for academia and industry. They will be able to embrace the life science's industrialisation thereby filling a vital skills gap in UK industry. These students will be able to bridge the divide between academia/industry and development/application across the physical/mathematical sciences and life sciences, as well as the human-machine interfaces. The technology programme of the CDT will empower our students as serial inventors, not reliant on commercial solutions.
CDT Network-Communication & Engagement: The CDT will shape the landscape by bringing together >160 research groups with leading players from industry, government, tech accelerators, SMEs and CDT affiliates. The CDT is pioneering new collaboration models, from co-located prototyping warehouses through to hackathons-these will redefine industry-academic collaborations and drive technology transfer.
UK plc: The technologies generated by the CDT will produce IP with potential for direct commercial exploitation and will also provide valuable information for healthcare and industry. They will redefine the state of the art with respect to the ability to make, measure, model and manipulate molecular interactions in biological systems across multiple length scales. Coupled with industry 4.0 approaches this will reduce the massive, spiralling cost of product development pipelines. These advances will help establish the molecular engineering rules underlying challenging scientific problems in the life sciences that are currently intractable. The technology advances and the corresponding insight in biology generated will be exploitable in industrial and medical applications, resulting in enhanced capabilities for end-users in biological research, biomarker discovery, diagnostics and drug discovery.
These advances will make a significant contribution to innovation in UK industry, with a 5-10 year timeframe for commercial realisation. e.g. These tools will facilitate the identification of illness in its early stages, minimising permanent damage (10 yrs) and reducing associated healthcare costs. In the context of drug discovery, the ability to fuse the power of AI with molecular technologies that provide insight into the molecular mechanisms of disease, target and biomarker validation and testing for side effects of candidates will radically transform productivity (5-10 yrs). Developments in automation and rapid prototyping will reduce the barrier to entry for new start-ups and turn biology into an information technology driven by data, computation and high-throughput robotics. Technologies such as integrated single cell analysis and label free molecular tracking will be exploitable for clinical diagnostics and drug discovery on shorter time scales (ca.3-5 yrs).
Entrepreneurship & Exploitation: Embedded within the CDT, the DISRUPT tech-accelerator programme will drive and support the creation of a new wave of student-led spin-out vehicles based on student-owned IP.
Wider Community: The outreach, responsible research and communication skill-set of our graduates will strengthen end-user engagement outside their PhD research fields and with the general public. Many technologies developed in the CDT will address societal challenges, and thus will generate significant public interest. Through new initiatives such as the Makerspace the CDT will spearhead new citizen science approaches where the public engage directly in CDT led research by taking part in e.g hackathons. Students will also engage with a wide spectrum of stakeholders, including policy makers, regulatory bodies and end-users. e.g. the Molecular Quarter will ensure the CDT can promote new regulatory frameworks that will promote quick customer and patient access to CDT led breakthroughs.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S023518/1 01/10/2019 31/03/2028
2596635 Studentship EP/S023518/1 02/10/2021 30/09/2025 NIALL McINTYRE