Identifying structural and biophysical parameters controlling cytokine signaling
The geometrical requirements needed to modulate signal activation by a cytokine-cytokine receptor complex still remain very poorly defined. A clear delineation of these geometrical parameters would provide us with critical insight into the complex biology of cytokines and would allow us to design more specific and less toxic cytokine-based therapies.
We are working to systematically define how alteration on the binding topology of the cytokine-cytokine receptor complex impact signal activation and potency. To accomplish this, we are combining protein engineering with quantitative mass spectrometry and structural biology to introduce well-defined structural modifications in both the cytokine and the cytokine receptor to study their impact in signal activation nature and potency.