National Resource for Cell Analysis and Modeling

National Resource for Cell Analysis and Modeling

Research Emphasis

The National Resource for Cell Analysis and Modeling (NRCAM) is developing methods for modeling cell physiologic processes in the context of the actual three-dimensional structure of individual cells. Approaches in computational cell biology are coupled with high-resolution light microscopy to facilitate the interplay between experimental manipulation and computational simulation of specific cellular processes.

Current Research

NRCAM is developing the Virtual Cell, a general computational framework for modeling cell biological processes. This new technology associates biochemical and electrophysiologic data describing individual reactions with experimental microscopic image data that describes their subcellular locations. Individual processes are integrated within a physical and computational infrastructure that will accommodate any molecular mechanism. Current development of the Virtual Cell is focused on expanding the generalized mathematical descriptions to include additional cell biological mechanisms, enhancing accessibility to biologists studying different biological processes, and integrating the interface with a database of images and reaction mechanisms. Current applications of the Virtual Cell include studies of calcium dynamics in neuroblastoma cells and Purkinje cells and studies of intracellular RNA trafficking in oligodendrocytes. Additional collaborative research projects include modeling diffusional processes in mitochondria, nuclear transport, and aspects of cell motility.

Resource Capabilities

Methods

Methods include computational modeling and simulation of cell biology and quantitative light microscopy.

Instruments

Microscopy instrumentation includes four confocal laser scanning microscopes, including ultraviolet excitation and real-time imaging, nonlinear optical microscopy utilizing a titanium sapphire pulsed laser, confocal-based fluorescence correlation spectroscopy, wide-field imaging workstation with cooled charge-coupled device and rapid excitation filter wheel, and dual-wavelength spectrofluorometry. Access to the facilities and technical staff is open to all researchers.

Computational resources include two dedicated environmentally controlled server rooms housing a variety of hardware resources, currently with >600 gigaflops computer power, >20 terabyte storage, and >500 gigabits per second switching bandwidth, and undergoing continuous expansion.

Access to the Virtual Cell Modeling software is available via the Internet through a JAVA-based interface.

Software

Software includes Virtual Cell, which is used for computational modeling and simulation, and various image processing, analysis, and visualization software packages.

Training Opportunities and Workshops

The Virtual Cell short course is held each June. A live-cell-microscopy workshop is held each fall.

Publications

1. Hernjak, N., Slepchenko, B. M., Fernald, K., Fink, C. C., Fortin, D., Moraru, I. I., Watras, J., and Loew, L. M., Modeling and analysis of calcium signaling events leading to long-term depression in cerebellar Purkinje cells. Biophysical Journal 89:3790–3806, 2005.

2. Mayya, V. and Loew, L. M., STAT module can function as a biphasic amplitude filter. Systems Biology 2:43–52, 2005.

3. Moraru, I. I. and L. M., Intracellular signaling: spatial and temporal control. Physiology 20:169–179, 2005.

4. Slepchenko, B. M. and Terasaki, Bio-switches: What makes them robust? Current Opinion in Genetics and Development 14:428–434, 2004.