2nsd year post-graduate research student - MIBTP program, BBSRC funded

Main Supervisor: Dr Mark Wall, School of Life Sciences

Second Supervisor: Professor Magnus Richardson, School of Mathematics

Project Title: Whole cell patch clamp and computational modelling to explore the effects of injection of protein aggregates on intrinsic neuronal properties in vitro.

Confocal Images of a pyramidal neuron (top) and OLM interneuron (bottom) using Alexaflour 488 dye following whole cell patch clamping.

Having graduated from my undergraduate degree in Medical Genetics from the University of Leicester in July 2016, I started on the MIBTP program here at Warwick. I have completed the training year which consisted of:

• Taught modules: Statistics, Programming, RNA seq, Computational Modelling
• Industry Placement: Technology transfer and patents - Alta Innovations, University of Birmingham
• Miniproject 1: McCutcheon lab at the University of Leicester. Effect of energy substrate availability on Dopamine signalling
• Miniproject 2: Wall lab at the University of Warwick. Exploring the effects of the neuromodulator adenosine on intrinsic properties of different cells within the hippocampal microcircuit.

Project Abstract (from postgraduate symposium 2018):

Neurodegeneration: what effect does oligomeric tau protein have on the intrinsic properties of neurons?

Neurodegenerative disorders are typically characterised by protein aggregation and the formation of inclusion bodies, which disrupt cellular function. I will investigate the effect of proteins alpha synuclein (αSyn) and Tau, which are key to the pathology of Parkinson's disease and Alzheimer's disease respectively. The reason that cells are so susceptible to these oligomers is unclear.

Using a combination of electrophysiology and computational modelling, my PhD will explore the effect that αSyn and Tau oligomers have on neuronal properties.Tau oligomers have been generated, and whole cell patch clamp recording used to evaluate the effect of their injection into CA1 pyramidal neurons. A number of exciting observations have been made relating to both the intrinsic properties and action potential dynamics using Matlab and Julia programs. Immunohistochemistry has also been used to investigate the localisation of the injected Tau relative to endogenous tau. Finally, connected layer V cortical pyramidal neuron pairs will be recorded to determine if there is an effect of Tau oligomer presence on synaptic transmission.

For the next stage of my PhD, I will adapt the dynamic IV computer model for dopamine neurons in the SNpc, generate αSyn oligomers and begin to evaluate their effect.

Emily Hill

E.Hill.2@warwick.ac.uk

Lab C117