2015 Beckman Symposium   

Sin Urban, PhD

Presentation Date:

Sin Urban, PhD

Rhomboid enzymes: versatile scissors inside the cell membrane

Johns Hopkins University - School of Medicine

Molecular Biology & Genetics


Membranes form the living border between cells and the outside world. All life depends on reactions that occur within membranes, from algae harnessing solar energy through photosystems to the human brain propagating electrical impulses along neurons. Guardians of this frontier are specialized, membrane-immersed proteins, yet understanding protein function in the membrane environment is one of the great enduring mysteries of biochemistry. We have been investigating rhomboid proteases, which are perhaps the largest family of membrane enzymes. Rhomboid proteases are endowed with the extraordinary ability to hydrolyze protein segments within the membrane. This ancient family of membrane-immersed enzymes plays key roles in bacterial growth, animal development, malaria parasite invasion, and mitochondrial quality control. Although we have solved rhomboid structures, translating these high-resolution images into a sophisticated understanding of rhomboid’s functional properties remains challenging. We are applying new spectroscopic, thermodynamic, and enzymatic methods to rhomboid proteases and their substrates reconstituted into defined membranes. These approaches indicate that rhomboid proteases have evolved unexpected properties specifically by virtue of being immersed inside the membrane. We seek to integrate these biophysical insights with animal studies ultimately to develop therapeutics for a variety of diseases.


Sin Urban is Associate Professor of Molecular Biology and Genetics at the Johns Hopkins University School of Medicine (USA) and the Howard Hughes Medical Institute (HHMI). He received his B.Sc. in Honours Genetics at the University of Alberta (Canada), where he studied viral replication. He obtained a Ph.D. in 2002 from the University of Cambridge (UK), conducting research in the MRC Laboratory of Molecular Biology, where he discovered that the signaling factor rhomboid is an intramembrane protease. Dr. Urban continued his work in Cambridge as a JB & Millicent Kaye Prize Fellow in Cancer Studies, and then in 2004 started his independent lab as a Harvard Fellow at Harvard Medical School. Dr. Urban was recruited to Johns Hopkins in 2006, where his research now encompasses investigating the pathogenic functions and biophysical mechanisms of intramembrane proteases. Dr. Urban is also Director of Admissions of the Biochemistry, Cellular and Molecular Biology Ph.D. program at Johns Hopkins, and serves on the Editorial Boards of the Journal of Biological Chemistry and BBA Biomembranes. Dr. Urban has received numerous awards for his work, including: the Genetics Society of America Sandler Award for Outstanding Ph.D. Dissertation, Oxford University's Rolleston and MRC's Max Perutz Prizes for Original Research, HRH the Princess of Wales' Canada Scholarship for AIDS Research, the Cambridge Gedge Prize for Outstanding Observations in Physiology, and career awards from the Burroughs-Wellcome Fund, the David & Lucile Packard Foundation, and the Howard Hughes Medical Institute.

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