Model-based reasoning has been applied as an autonomous control strategy on the Low Energy Neutral Atom (LENA) instrument currently flying on board the Imager for Magnetosphere-to-Aurora Global Exploration (IMAGE) spacecraft. Explicit models of instrument subsystem responses have been constructed and are used to dynamically adapt the instrument to the spacecraft’s environment. These functions are cast as part of a virtual Principal Investigator (VPI) that autonomously monitors and controls the instrument. In the VPI’s current implementation, LENA’s command uplink volume has been decreased significantly from its previous volume; typically, no uplinks are required for operations. This work demonstrates that a model-based approach can be used to enhance science instrument effectiveness. The components of LENA are common in space science instrumentation, and lessons learned by modeling this system may be applied to other instruments. Future work involves the extension of these methods to cover more aspects of LENA operation and the generalization to other space science instrumentation.