PhD Studentship: Investigating Pesticide-Induced Neurotoxicity Using Lab-on-a chip Microfluidic Culture Models

Summary:

In collaboration with Syngenta Group, a leading technology company for sustainable agricultural innovation with 59,000 employees in more than 100 countries, this project will investigate the neurotoxicity and peripheral neuropathy triggered by exposure to chemical pesticides. Using cutting-edge microfluidic lab-on-a-chip culture models, we aim to explore the mechanisms underlying the neurotoxicity of pesticides. The project findings will ultimately lead to the development of safer and more efficacious pesticides. 

Introduction:

Chemical pesticides, commonly used in agriculture, can cause neurotoxicity in the peripheral nerves. The underlying mechanisms of pesticide-induced neuropathy remain unclear but may involve factors like acetylcholinesterase inhibition and oxidative stress. Current in vitro models for studying neuropathy have limitations, leading researchers to explore microfluidic lab-on-a-chip devices as a promising alternative. The Raouf lab at King’s College London has pioneered the use of microfluidic cultures as models of peripheral neuropathy and optimized protocols for assessing neuronal function. This project aims to investigate the effects of pesticide exposure on sensory and cortical neurons using these microfluidic cultures. 

PhD Project Goals:

The primary aim of this research is to delve into the impact of pesticide exposure on the structure and function of peripheral and central neurons using microfluidic cultures of rodent or human iPSC-derived neurons, either in single or co-culture setups. Specific objectives include:

Collaboration with Syngenta:

Syngenta will support this project by leveraging its expertise in toxicology, cell cultures, molecular  biology techniques offering guidance and materials during monthly meeting.  Their in-depth knowledge of in vivo neurotoxicity effects will help predict toxicity outcomes early in chemical development for safe design. 

Impact and Benefits:

The project seeks to identify and understand specific mechanisms and key events that contribute to chemical toxicity. The tools and pipelines developed during this PhD can be applied to early-stage development of new active ingredients, reducing project risks. As insecticide resistance is a growing concern, the research may contribute to the development of insecticides targeting ion channels.

Syngenta Product Safety facilities will be accessible to the student during their placement, offering opportunities to work on their inventions and address Syngenta's relevant problems. Jealott's Hill, Syngenta's international research centre, fosters collaborations with external partners, universities, and research centres. The centre funds numerous PhD studentships, emphasizing high-impact factor publications and providing a supportive and international environment. Students receive guidance and training from Syngenta staff, including expertise in -omics data analysis, toxicology, and systemic exposure. This phase is crucial for translating the PhD research into practical applications.

The student will interact with Syngenta scientists, participate in internal studentship events, and gain insights into industry practices, potentially leading to career opportunities post-PhD.

Furthermore, the student will present their work at the annual collaborators' conference, allowing a wider audience to view the results and fostering academic and industry connections.

This project combines cutting-edge microfluidic technology with Syngenta's expertise to investigate the neurotoxic effects of pesticides on neurons. It has the potential to improve our understanding of pesticide-induced neuropathy, contribute to safer chemical design, and provide valuable career development opportunities.

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