PhD Research Project: CENTA NERC - Brain-on-a-chip: an array to study nanoparticle-brain interactio
Engineered and incidental nanoparticles (NPs) are increasingly discovered in the environment, leading to concerns that they may be harmful to humans and biota. A key issues, regarding human health, is whether EINPs can enter the brain through the olfactory nerve. A recent study identified abundant nanoscale magnetite, resembling that formed by combustion, in human brains from polluted environments. Nanoscale magnetite has been linked to toxicity, via the production of reactive oxygen species (ROS), which has been associated with neurodegenerative diseases such as Alzheimer’s. This link to date is hypothetical, and challenging to demonstrate. The development of a model brain, may therefore allow further investigation of the processes occurring in the brain environment, associated with the presence of NPs and potentially leading to neurodegenerative diseases.
Developing of on-a-chip brain, based on microfluidic devices, may provide a solution to this challenge, by mimicking aspects of the brain, e.g. internal structure, cellular composition and fluid chemistry and enabling testing of interactions with NPs. Such microfluidic devices have the additional advantage of enabling automated, miniaturised, multichannel experimentation, thus enabling multiple spatially and temporally separated measurements, with a minimum consumption of materials and reagents. Increasingly such devises can have complex designs, integrating operations, such as cellular structure and composition, fluid chemistry and the effect of different array designs and materials, in reproducing biological functions.
The proposed project aims to innovate by assessing interactions between a variety of engineered and incidental NPs and a simulated brain environment, thus assessing the potential of in situ ROS generation and its effects on the brain cellular structure and cerebrospinal fluid composition and potential changes in protein properties.
For the development of a brain-on-a-chip, a microfluidic platform design developed around the key components of structure (cellular and chemical), composition and interactions with NPs. This first step will involve the design and fabrication of the chip, followed by optimisation of the fabrication parameters in order to improve performance and ensure reliable operation. This will be followed by experimental characterisation of alternative designs and finalising a prototype.
The optimum design will then be tested with a range of NP types, sizes and compositions. Multiple parameters will be studies, e.g. effects on the physicochemical properties of the NPs, chemical and structural compositions of the simulated brain components. Measurements will be carried out in a variety of set-ups to ensure method reproducibility and samples will be characterised by analytical techniques for the assessment of organic (e.g proteins) and inorganic (.e.g NP component) composition. A sub-set of assays will be studied in depth, including a full characterisation of individual components of spent chips to ensure a thorough system understanding.
In addition to completing an online application form, you will also need to complete and submit the CENTA studentship application form available from www.centa.org.uk.
CENTA studentships are for 3.5 years and are funded by the Natural Environment Research Council (NERC). In addition to the full payment of their tuition fees, successful candidates will receive the following financial support.
Annual stipend, set at £14,296 for 2016/17
Research training support grant (RTSG) of £8,000
CENTA students are required to undertake from 45 days training throughout their PhD including a 10 day placement.
1. Maher, B. A.; Ahmed, I. A. M.; Karloukovski, V.; MacLaren, D. A.; Foulds, P. G.; Allsop, D.; Mann, D. M. A.; Torres-Jardón, R.; Calderon-Garciduenas, L., Magnetite pollution nanoparticles in the human brain. Proceedings of the National Academy of Sciences 2016, 113 (39), 10797-10801.
2. Kilic, O.; Pamies, D.; Lavell, E.; Schiapparelli, P.; Feng, Y.; Hartung, T.; Bal-Price, A.; Hogberg, H. T.; Quinones-Hinojosa, A.; Guerrero-Cazares, H.; Levchenko, A., Brain-on-a-chip model enables analysis of human neuronal differentiation and chemotaxis. Lab on a Chip 2016.
2. Valsami-Jones, E.; Lynch, I., How safe are nanomaterials? Science 2015, 350 (6259), 388-389.
3. Di Terlizzi, R.; Platt, S., The function, composition and analysis of cerebrospinal fluid in companion animals: Part I - Function and composition. Vet. J. 2006, 172 (3), 422-431.
4. Nightingale, A. M.; Krishnadasan, S. H.; Berhanu, D.; Niu, X.; Drury, C.; McIntyre, R.; Valsami-Jones, E.; deMello, J. C., A stable droplet reactor for high temperature nanocrystal synthesis. Lab on a Chip 2011, 11 (7), 1221-1227.
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