Detailed Investigation of Human Epilepsy: Growing Human Neuron Cell Bodies to Regular Lattice Structures on Controllable Silicon Chips

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Engineering

Abstract

This research aims to increase understanding and to begin to explain the synchronisation effects that neurons undergo in the brain. In particular, the research is interested in the abnormal synchrony that occurs during epilepsy where conventional thinking is that the neurons all fire simultaneously. However, there are approximately 40 different types of epilepsy, each with a distinctive EEG signature . As such, we hypothesise that the neurons undergo very different routes to synchronisation which in turn implies that the synchronisation pathway is seizure-type dependent. This could be due to the way in which the neurons in the network are connected physically to one another, known as the architecture of the network and the relative firings of the neurons. Thus, by identifying the network architectures and temporal behavior of the neurons responsible for such abnormal synchrony, one would gain an insight into the fundamental circuitry involved in seizure and the differences between seizure types. Murray's group at the University of Edinburgh's IMNS have developed a platform technology which forces cells to grow along lines that are defined on a semi-conductor substrate using inorganic materials. The technique has been used to pattern stem cells, rat neurons and glia. They are interested in expanding the technique both to pattern cells in other configurations and also to different cell types.Unsworth's group at the University of Auckland are interested in the synchronisation effects that occur in lattices of coupled neurons with particular emphasis on the abnormal synchrony that occurs in human epilepsy. Their work adapted the well-known Kuromoto coupled oscillator model to allow for the study of neuronal synchronisation. Such work demonstrated, theoretically, that the synchronisation was indeed dependent on the architecture of the network and was awarded the Neurological Foundations Goddard Prize. In addition, in unpublished work, Unsworth has investigated Artificial Neural Network lattice models and Chaotic Neural Network lattice models to describe epilepsy. These models have also confirmed theoretically that synchronisation is architecture dependent. Moreover, they have revealed how the synchrony exists on many temporal and spatial scales (i.e where different groups of neurons switch on and off independently to other groups of neurons) rather than all firing simultaneously as is commonly thought. They are interested to develop new computer models where the inference is derived directly from in vitro experiment with human neurons grown to regular lattice arrangements.Through this proposed partnership, both groups needs will be addressed. This collaboration intends to firstly exploit and expand the platform technology developed by the Edinburgh group to grow neurons, not only along lines, but also to localise the cell bodies of the neurons to regular lattice structures and individually control them by Multi-Electrode Arrays (MEAs). Secondly, it intends to culture a new cell type; the human neuron on chip thus strengthening its existing filed patent. Expanding the platform technology in such a way, will facilitate the Auckland group, to undertake investigations into the in vitro behaviour of human neurons grown to regular lattices and to develop new precise models of human epilepsy.Thus, this fellowship aims to begin to bring to bear techniques developed in Edinburgh on future detailed explorations of epileptic signalling patterns in patterns of cultured, real neurons. The primary aim of the visit is to transfer cell-patterning technology to Unsworth's lab and thus launch an ambitious, long-term collaborative research programme.

Publications

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Hughes MA (2014) Cell patterning on photolithographically defined parylene-C: SiO2 substrates. in Journal of visualized experiments : JoVE

 
Description That human neural and other cells can be patterned on silicon using a material (parylene) that is compatible with silicon chip manufacture.
Exploitation Route The technique will be used as part of a new EPSRC project (EP/K034510/1) to guide cancer cells toward sensors that will diagnose the tumour's status and thus guide radiotherapy.
Sectors Healthcare

 
Description The finding - that human cells follow parylene tracks on silicon chips - will be used as part of a new EPSRC project (EP/K034510/1) to guide cancer cells toward sensors that will diagnose the tumour's status and thus guide radiotherapy.
Sector Healthcare
 
Description University of Auckland 
Organisation University of Auckland
Country New Zealand 
Sector Academic/University 
PI Contribution Dr. Charles Unsworth was funded to travel and work in Edinburgh and this collaboration has generated a long-term sustainable partnership between the Universities of Edinburgh and Aukland.
Collaborator Contribution Dr Unsworth manufactured silicon substrates for patterning in Edinburgh and subsequently collaborated with medical researchers in Auckland to show that human cells can be patterned on these substrates.
Impact Many research papers and an EPSRC proposal (unfunded) to better understand the mechanism behind cell patterning by parylene on silicon.
Start Year 2009