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My overall research interest is the processing and transformation of information within the nervous system. The long-term ambition being to understand the processes and principles which underlie the distribution and function of signalling systems within the architecture of the cell, and determine its fate.
The overarching theme of my research over recent years has been the search for ways to extract pragmatically useful knowledge from the wealth of attainable neuroscience information. This is a central theme in many fields where new technologies generate vast data sets but understanding is lagging. Core to this theme is the modeling of function and dysfunction at a number of levels of abstraction.
This is exemplified in the development and use of organotypic cultures of rodent brain for modeling neuropathology. This system retains synaptic connectivity, cell type diversity and electrical activity in a controlled in-vitro system. (McManus et al 2004; Sadgrove et al 2006). This work is part of a long-standing collaboration with colleagues in the Clinical Neurosciences department combining our imaging and tissue-culturing expertises to allow analysis of neuronal function. The success of this work has translated into a spin-out company, Capsant Neurotechnologies, that we co-founded in 2002, and with which we continue to collaborate in the development of new models of neuropathologies.
A fascinating parallel development has arisen out of collaborations with colleagues in Electronics and Computing where we have sought to model the computational function of neurones as cellular automata. The central theme is the notion that the computational function of a neurone is a stable outcome of the cellular regulatory processes. If this posit holds, then it becomes possible to attempt to abstract the computational function and test through modeling the degree to which the system behaviour has been captured (Claverol et al 2002a,b). This cellular automata approach holds out the promise of allowing the computation of the behaviour of very large cell assemblages in order to look for emergent behaviours. An additional spin-off of using a hardware description language to define the automata has been the possibility of translating these automata into physical devices that combine processing and memory and could become an alternative form of computer architecture. This work has a way to go before its utility can be truly evaluated.
To come full circle, the testing of the automata concept with arrays of cultured real neurones on MEAs has now become possible because of technological developments within Capsant that should allow us to characterize the circuit formation inherent in a given cell type in the absence of the normal long-range developmental cues. This is now part of a collaborative CASE project.
Interest in the control of neuronal excitability, information transfer, and the role of Ca++ signalling led to the adoption of optical imaging techniques. Principally, the adoption of Confocal laser Scanning Microscopy. This powerful technique allows for the quantitative determination of the 3-D distribution of fluorescent molecules to a resolution of 300nm. We are exploiting this system to study neuronal structure and function within functional brain slices.
The multitude of possible uses for confocal microscopy in the biological sciences has led to a number of fruitful collaborations extending beyond the neurosciences.
Hopefully (in my dreams), these strands will come together to help us begin to understand the self-organising principles that I believe must underlie the function of the CNS.