The Urban Lab studies an extraordinary class of enzymes that catalyze reactions inside the cell membrane. These rhomboid intramembrane proteases cut proteins to initiate signaling between cells as a form of communication that organizes embryo development. Rhomboid proteases are conserved in nearly all forms of life, arguing that they are ancient and fundamental. By exploring this surprising biological diversity, we next discovered rhomboid enzymes function in the invasive cycle of deadly pathogens including the malaria parasite.
More recently, we refocused our lab to study the biophysics of how these unusual enzymes function immersed inside the cell membrane, which is a challenging environment for catalysis. In particular we are interested in:
1. How is hydrolysis within membrane environments accomplished by intramembrane proteases and how is specificity achieved?
2. What is the role of rhomboid proteases in pathogenic microbes including the malaria parasite and flesh-eating ameba?
3. What can we learn about the function of rhomboid intramembrane proteolysis and signalling throughout evolution?
We are using a combination of structural biology, membrane biophysics, cell biology, and synthetic chemistry to address these issues. Our studies may have therapeutic implications since rhomboid intramembrane proteolysis plays a central role in malaria infection and Parkinson’s disease pathogenesis.