The Center for Multiscale Modeling of Biological Systems focuses on developing computational methods and tools for investigating a wide range of spatiotemporal scales in biological systems with an emphasis on new techniques for bridging between these scales. In particular, our Technology Research and Development (TR&D) projects focus on:

  • Molecular modeling and simulations, with an emphasis on developing tools to identify functional substrates and interaction mechanisms for proteins and their complexes/assemblies involved in synaptic signaling (TR&D1)
  • Cell modeling, with an emphasis on developing tools to handle spatial and molecular complexity inherent to neuronal signal transmission (TR&D2)
  • Network Modeling, yielded many novel insights, in particular, the identification of common network motifs such as feedback and feed forward loops that give rise to specific classes of signal processing characteristics – like switching, oscillation, and adaptation. (TR&D3)
  • Image processing and analysis, with an emphasis on analysis of cell and tissue organization in support of computational modeling (TR&D4)

Our technology development is directly driven by several experimental Driving Biomedical Projects (DBP) with top research groups across the country:

  • Glutamate transport: The molecular mechanism of neurotransmitter binding, uptake and signaling by excitatory amino acid transporters and other secondary transporters. Investigating the structural-dynamic-functional aspects of glutamate transporters, S. Amara (NIH), DBP1
  • Synaptic signaling: The activation of calmodulin-dependent protein kinase and other molecular mechanisms triggered within the first minute inside spines leading to long-term memories. Modeling activation of CaMKII in spines, M. Kennedy (CalTech), DBP2
  • Dopamine transporter (DAT) function: Spatiotemporal models of dopamine transporter function regulation in neurons, including the interaction with acetominophen, endocytosis and intracellular trafficking. Spatiotemporal model of DAT function regulation in neurons, A. Sorkin (Univ. of Pittsburgh), DBP3
  • T-cell signaling: Image-derived spatiotemporal modeling of IL-2 inducible T-cell kinase regulation of T-cell signaling, C. Wuefing (Univ. of Bristol), DBP4
  • Neural circuits (Completed): Assembly of large scale serial section transmission electron microscopy image stacks for neuronal circuit reconstruction. Functional connectomics: Terascale reconstructions of cortical circuits, C. Reid (Harvard), DBP5
  • Transcription and chromatin structureThe DBP will drive (i) the extension of protein structure and dynamics analysis software such as ProDy to chromo-some- scale modeling using imaging-derived contact maps and (ii) the development of probabilistic spatial models from movies of one or more image fluorescent spots, from which to derive contact maps and other spatial measurements.
  • Structure and function of synapses will be used to construct spatiotemporally realistic models for neuronal dendrites, axons and synapses, and subcellular components such as ER, mitochondria and endosomes and simulate synaptic function and LTP.
  • Scalable modeling This DBP will drive the development of integrated tools for model development visualization, calibration, and analysis that are much needed for any modeling project, and the improvement of generative modeling tools that capture biophysical relationships independent of the details of image acquisition and can be used in conjunction with model calibration to study mechanism.

Beyond our Driving Biomedical Projects, we engage in a large number of other collaborations with experimental and computational research groups.

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