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Our research grouping has inter-disciplinary expertise in determining the mechanisms by which signal transduction modulates cell and organ behaviour under normal and disease conditions. The functional roles of living biological systems are controlled by the integration of many different molecular pathways. These can be incredibly complicated to understand whether one is considering events at the single cell, interactions between cells in complex multicellular systems or even between organs. T hese processes are finitely regulated in both time and space. Our objectives are to utilise state-of-the-art bioimaging equipment to advance our understanding of spatiotemporal signalling dynamics at different system levels in vitro and in vivo. In particular: (i) the use of fast spinning disk laser scanning fluorescent microscopy with photoactivation (flash photolysis, FRAP and FRET) and electrophysiology to study the molecular cell physiology with the goal of increasing our understanding ho w individual cells process biological information. (ii) whole body 3-D bioluminescent and biofluorescent imaging to track cellular movement and activation between different organs with the aim of developing new understandings of disease progression. In combination the equipment will enable the investigation of signalling events from cells to tissue to whole body, from in vitro to in vivo.

fMRI at 4.7T on four awake-fixating macaque will demonstrate analysis mechanisms for the temporal structure of sound. High-quality sound delivery and field coils optimised for both subcortical and cortical structures will be used. Sparse acquisition (allowing optimum BOLD signal-to-noise ratio) and continuous acquisition (allowing detailed time series for effective connectivity analyses) will be used. Volume-of-interest analyses will include the inferior colliculus, medial geniculate body and co rtical core, belt and parabelt areas. These areas have been successfully imaged in pilot work, and will be precisely mapped in each subject (using tonotopy and bandwidth for cortical areas). The work will examine intrinsic differences in the auditory BOLD response in the different areas, and the effect of varying temporal structure on the BOLD response of areas and effective connectivity between them. Three levels of temporal structure will be assessed: i) fine structure (millisecond level); ii) envelope responses defined systematically by the amplitude modulation transfer function (tens to hundreds-of-millisecond level) and iii) sound-sequence level (level of seconds). Parallel behavioural work at the first two levels (outside the scanner) will enable the comparison of behaviour as a systematic function of temporal structure with BOLD responses defined in the same way.