Currently, our studies of Toll signaling are centered on three research areas:

 

1. Dissecting the Mechanism of Signal Transduction. Toll-mediated inactivation of the inhibitor Cactus requires signal transduction by MyD88, Tube, and Pelle. We have demonstrated that these three proteins function in signaling by forming a trimeric protein complex. We have used molecular genetic, biochemical, and biophysical approaches to define and mutate the precise sites of interaction in the trimer, generating powerful reagents for the dissection of the signaling mechanism. We have also demonstrated a role for protein phosphorylation in regulating the pathway both prior to and during signal transduction.

  

2. An Informatics-Based Approach to Decoding Transcriptional Control at a Global Level.  The Toll pathway operates in parallel with a second signaling system –the Imd pathway–to govern innate immune responses. Both systems rely on NF-kB related transcription factors to regulate gene expression. Using a molecular genetic approach, we have demonstrated that cis-acting control elements act as a specificity code for the response to either or both pathways. Using our understanding of these elements to inform bioinformatic studies, we have mapped out the global system of control for the major innate immune reponses in flies.