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Study of nanoparticle toxicities with C. elegans using a microfluidic system

Faculty of Engineering and Physical Sciences

Applications accepted all year round Competition Funded PhD Project (Students Worldwide)

About the Project

With the extensive use of nanomaterials in consumer and medical products, there are growing concerns about the nanoparticle biosafety. Conventional cell-based toxicity assays do not provide complex organism-level information, and the use of mammalian animals is costly, time-consuming, and requires a high level of skills and considerations for animal welfare. There are needs to develop convenient and cost-effective means for toxicity tests using whole non-mammalian organisms. C. elegans, with its transparent body, completely sequenced genome, and a high degree of homology with humans, is a highly attractive system for nanotoxicology studies. Their short generation time, low cost, and ease of maintenance have conferred significant advantages. However, the current methods for handling C. elegans are time-consuming and labour-intensive. Microfluidics is fast emerging as a leading tool for C. elegans analysis as the microfluidic channel size is on the same scale as those of worms, enabling precise fluid and worm manipulations, which also allows high-throughput monitoring. The overarching goal of this project is to develop a high-throughput microfluidic platform (named Whole Organism Reproduction Microfluidic Device (WORM Device)) to incubate C. elegans, separate each generation of the animal and to study the responses of worms to nanoparticle exposures, and its genotoxic effects carried over their progenies on-chip. This will involve:
1. Develop a microfluidic device consisting of multiple storage areas, separated by an array of posts and openings, which allows separation of offspring-worms from parent-worms.
2. Evaluate the effects of short- and long term nanoparticle exposure to worms and their progenies. We will study the survival rate, lifespan, growth, motility, biodistribution and reproduction of the animal on-chip, which depend on nanoparticle size, shape, and surface-functionalisation.
3. Investigate the impact of nanoparticles on C. elegans ageing of (i) the different types of particles, (ii) epigenetic effects, such as missense variants of the ryanodine receptor and consequences of chromatin modifications, through successive generations.

Funding Notes

Please refer to the University of Leeds website for funding information.

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