• Computational Modeling
• Imaging
• Systems Engineering

A core proficiency in biology has been essential to MICA development.

MICA in Action

• Optical sorting of macrophage cells 40X slower
  (1.34MB WMV by Thomas Perroud)
• Cell sorter animation
  (110KB Flash animation by Thomas Perroud)

Image Gallery

Computational Modeling

Sandia’s computational modeling capability has been crucial to MICA’s success. For example, hypotheses generated through computations drove experimental researchers to search for and discover a number of specific events that may otherwise have been undetected.

Overall, MICA’s computational biology efforts are aimed at two main goals:

• Generate hypotheses that can be tested experimentally. To this end,  we develop and use network inference techniques to predict phenomena such as the following:
  • Protein-protein and protein-ligand interactions (Faulon et al. Bioinformatics 2008)
  • Phosphorylation sites (Gray et al. 2008)
  • Activation/inhibition rules between transcription factors and transcripts (Martin et al. 2007).

• Explain observed phenomena. In particular, we aim to elucidate the kinetics and key controlling components of the innate immune response to infectious stimuli, which today is poorly understood. A key area is research is focused on explaining the dynamic behavior of the transcription factor NF-κB that occurs when host cells (such as the HeLa macrophage) are challenged by infectious stimuli (including various liposaccharides or LPS chemotypes).

Using a simulation-based computational model, we have investigated how different LPS chemotypes and dosage levels elicit different responses in immune cells. Our simulations reveal a distribution of dynamic patterns of NF-κB responses.

The damped oscillatory pattern for the wild-type case is expected to be robust against the undesirable perturbation of kinetic-rate variables. For mutants with the A20 gene knocked out, both single-peaked and damped oscillatory patterns are most probable, while for mutants with the double IκB genes knocked out, the sustained oscillation pattern becomes more prominent.