Biomedical Application Projects

    Presynaptic calcium dynamics and neurotransmitter release.
    This project includes related experimental work from the laboratory of Steve Meriney in the Department of Neuroscience at the University of Pittsburgh. Using DReAMM and computer-aided-design software we have developed a realistic model of an active zone, the nerve cell architecture that underlies release of neurotransmitter molecules during synaptic transmission.  Using this active zone model, we run MCell simulations of nerve excitation, calcium influx and binding, and neurotransmitter release.  We constrain and validate the model and simulations using previously existing and newly acquired experimental data (e.g., calcium imaging of stimulated nerve-muscle preparations), and use the simulations to make quantitative predictions for spatial and functional relationships between calcium channels, calcium binding sites, synaptic vesicles, and other components of active zone architecture.  Future extensions will include multiple stimuli and other synapses, i.e., paradigms that encompass functional changes (plasticity) in synaptic physiology.  Such coupled, quantitative experimental and computational studies are essential to future interventions for a wide variety of neurological and psychiatric disorders, as well as a deeper understanding of fundamental human behaviors like learning and memory.

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