Thousands of agents are neuroprotective in animal stroke models but have not translated to the clinic, at least in part due to species divergence. We have developed a bespoke microfluidics stroke model using rodent neuronal cells which we propose to replace with human neuronal cells. This human-based model is designed to reduce and replace the use of animals in stroke research and has additional health benefits of better recapitulating human pathophysiology, providing greater translational value.

Aims & objectives

This PhD project aims to:

• develop, validate and apply our bespoke microfluidics stroke model using with human induced pluripotent stem cell (iPS)-derived neuronal cells rather than rodent neuronal cells in; and
• make the enhanced, “humanised” microfluidics model the “go-to” model for some areas of stroke research that currently require the use of animals.

We have developed a ‘stroke-on-a-chip’ microfluidic model that currently uses mouse primary neuronal cultures. The objectives of this work are to develop, validate, and apply this model using human iPS-derived neuronal cells instead of rodent neuronal cultures to transform it into a human-based stroke model. You will have access to support for all methodologies and established protocols we are proposing.

Project features

Two main features make our model stand out from other human stroke models:

• Our model replicates the spatial and temporal gradients of oxygen glucose deprivation spreading from ‘core’ to ‘penumbra’ found in vivo which cannot be achieved using existing in vitro systems. This will provide crucially important information on critical thresholds of OGD that induce: loss of neuronal viability, connectivity, electrical function and protein synthesis in core and penumbra, all of which could be salvaged by interventional therapeutics.
• Our multi-chamber microfluidics system allows quantitative, real-time measurements of cell-cell responses in remote and proximal regions to the ischaemic insult. This crucially important knowledge on spatial definition of cellular reactivity and their modulation by therapeutics cannot be acquired in conventional systems.

In summary, this PhD position is a unique opportunity to replace the use of animals to investigate stroke pathomechanisms and prospective therapeutics, and help improve clinical relevance of preclinical stroke research.

Further information

You will be expected to contribute to the establishment and maintenance of iPS derived neuronal cultures and within the Carswell and Zagnoni labs at Strathclyde and Gibson lab in Nottingham. You will be expected to receive training in neurobiology and engineering techniques, and work in a multidisciplinary environment with a focus on stroke research. In addition, you will be expected to receive training in 3Rs research and organ-on-chip technologies and follow and adapt existing protocols in the development of this model. 

Further information on the Development of 'human stroke-on-a-chip' model to replace rodent stroke models project.