Revealing the Structure and Function of Membrane Proteins Through Nanotechnology
Membrane proteins are involved in numerous vital biological processes, including transport, signal transduction and the enzymes in a variety of metabolic pathways. Integral membrane proteins account for up to 30% of the human proteome and make up more than half of all currently marketed therapeutic targets. Unfortunately, membrane proteins are inherently recalcitrant to study using the normal toolkit available to scientists, and one is most often left with the challenge of finding inhibitors, activators and specific antibodies using a denatured or detergent solubilized aggregate. Often, since membrane proteins are inherently insoluble and prone to aggregation and oligomerization in solution, the active state of interest is obscured. The Nanodisc platform circumvents these challenges by providing a self-assembled system that renders typically insoluble, yet biologically and pharmacologically significant, targets such as receptors, transporters, enzymes, and viral antigens soluble in aqueous media. Because Nanodisc constructs provide a native-like bilayer environment that maintain a target’s functional activity, they are a versatile tool in the study of membrane proteins such as ion channels, GPCRs, cytochrome P450s, blood coagulation factors, various toxins and viral entities as well as a plethora of pharmaceutical targets. In addition to the opportunities in drug discovery, Nanodiscs provide a nanometer scale vehicle for the in vivo delivery of amphipathic drugs, therapeutic lipids, tethered nucleic acids, imaging agents and active protein complexes. In my presentation I will focus on recent uses of the Nanodisc technology in seeking mechanistic understanding of metalloprotein oxygenases, integrin and KRas4b signaling and Alzheimer’s disease intervention.
Stephen G. Sligar
Swanlund Endowed Chair, University of Illinois Urbana-Champaign
Stephen G. Sligar received his Ph.D. in Physics from the University of Illinois in 1975. Dr. Sligar served on the faculty in the Department of Molecular Biophysics and Biochemistry at Yale University and returned to the University of Illinois in 1982 where he was the I. C. Gunsalus Professor of Biochemistry. He now holds the University of Illinois Swanlund Endowed Chair and is Director of the School of Molecular and Cellular Biology. He is also a faculty member in the Department of Chemistry, the Center for Biophysics and Computational Biology and the College of Medicine. Dr. Sligar holds affiliate appointments in the Beckman Institute for Advanced Science and Technology, the Institute for Genomic Biology and The Micro and Nano Technology Laboratory on the Illinois campus. He is a Fellow of the Biophysical Society and the American Association for the Advancement of Science. Awards include a the Sober Lectureship from the American Society of Biochemistry and Molecular Biology, a Fulbright Research Scholarship, Senior Fellowship from the Japan Society for the Promotion of Science, an NIH MIRA Award, an NIH Merit Award and the Bert L. and Kuggie Vallee Visiting Professorship in Inorganic Chemistry at Oxford where he was a Fellow of Queens College. He is also a Fellow in the Jerome Karle Nobel Laureate World Innovation Foundation and an Academic Leadership Fellow from the Committee on Institutional Cooperation.
Molecular Engineering and Sciences Seminar Series
This weekly seminar brings together students, faculty and invited guests from various disciplines across campus to explore current trends in molecular engineering and nanotechnology. It is a forum for active interdisciplinary discussions. These talks are open to the public and attract a diverse audience of students and faculty.