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Like a fence that encloses a backyard, all of the body's cells are surrounded by membranes. Each membrane has its own complement of membrane proteins, which perform critical functions like letting things in and out of the cell, and keeping the inside of the cell informed of what's happening on the outside. Mark Dumont, Ph.D., professor of Biochemistry and Biophysics and Pediatrics, says that more than half of the drugs on the market today target membrane proteins.

Despite their importance, the structures and mechanisms that determine how these proteins work are not very well understood. In a recent study in Science, Dumont and collaborators at the University of Virginia and the Hauptman-Woodward Institute in Buffalo describe the structure of a particular membrane protein called Ste24p that is involved in cutting up other proteins in yeast. If there's a defect in this protein, yeast can't mate.

The obvious next question is, how is yeast's inability to reproduce relevant to people? It turns out, the human equivalent of the protein Ste24p, when mutated, causes progeria -- a premature aging disorder in which children develop hair loss, joint ailments, and heart disease, which they typically die of in their mid-teens. Dumont says that better understanding how this protein works -- in yeast and in people -- will help scientists to design a drug or other treatment for this devastating disorder and learn more about the human aging process.

Nadia Fedoriw, a technician in Dumont's lab, grows yeast used for protein production

Dumont is a senior investigator of the Membrane Protein Structural Biology Consortium, one of nine NIH-funded centers across the country that are trying to solve the structures of membrane proteins. He worked with Kathleen Clark and Nadia Fedoriw from Pediatrics and Sara Connelly from Biochemistry and Biophysics on the study.

The Provost's Multidisciplinary Award provides pilot funding for especially exciting scholarly research with a high probability of future support from external sources of funding. The Award is designed to foster collaboration between departments and across schools at the University of Rochester. Five diverse research projects at the University were selected as recipients of the sixth annual Provost's Multidisciplinary Awards. The initiative provides $250,000 each year to support faculty research that crosses disciplines.

Crystal structure of the preQ1-II riboswitch.

Department of Biochemistry and Biophysics Associate Professor Joseph Wedekind and members of his research group (Joseph Liberman, Mohammad Salim and Jolanta Krucinska) published a paper in the June 2013 issue of Nature Chemical Biology. The work describes the structure of an RNA molecule called the preQ1 class II riboswitch (featured on the journal's cover) that functions as a gene regulatory element for bacteria within the Firmicutes phylum, including human pathogens such as Streptococcus pneumoniae. The RNA structure is bound to the small molecule preQ1, which is the last soluble metabolite in the biosynthetic pathway that produces queuosine, a hypermodified base at the wobble position of certain tRNAs that promotes accurate genetic decoding. Because preQ1 is unique to the bacterial metabolome, the class II preQ1 riboswitch has potential as an antibacterial drug target.

The research was performed primarily at the University of Rochester and made extensive use of the Structural Biology and Biophysics Facility. The work also required the Stanford Synchrotron Radiation Lightsource (Menlo Park, CA), as well as Cornell High Energy Synchrotron Source (Ithaca, NY) where crystals were subjected to X-ray diffraction analyses. The work in Wedekind' lab was funded by the National Institutes of Health/ National Institute for General Medical Sciences (NIH/NIGMS).

The preQ1-II riboswitch structure reveals the chemical details of preQ1 binding in a pocket formed at the junction of three RNA helices. Complementary work from Wedekind's lab showed that preQ1 promotes a more compact shape that leads to blocking of a signal that is necessary for protein synthesis, which leads to lower levels of preQ1 in the cell. Of special note was the lab's observation that the mechanism of action used by the preQ1-II RNA riboswitch is entirely different than that used by the class I preQ1 riboswitch, whose structure and mode of preQ1 binding were reported previously by Wedekind's lab. Overall the results expand the known repertoire of metabolite-binding modes used by regulatory RNAs.

The Department of Biochemistry & Biophysics held its annual Awards Ceremony on Friday, May 17, 2013. Congratulations to our 2013 Graduates:

Our department was particularly honored this year to receive the University of Rochester's prestigious Wallace O. Fenn Award named after the first Chairman of the Department of Physiology. This award is given annually to a graduating student from any program within the Medical Center judged to have completed especially meritorious Ph.D. thesis research. This year, the award was given to two recipients for their thesis originality, creative thinking and excellence in research and both recipients were students from the Department of Biochemistry & Biophysics! Congratulations to Paul Black and Chenguang Gong! For a complete list of all awards, please see the Awards Ceremony Program. Photos of the event can be viewed on the B&B event photos page.

Dr. David Mathews will head one of the primary units within the recently announced $7.5M Center for Aids Research at the University. The NIH-funded center is one of only 18 in the country and brings together University scientists from numerous disciplines. Dr. Mathews, Associate Director of the Center for RNA Biology and Associate Professor within the Department of Biochemistry and Biophysics, will head the working group focused on the biology of the AIDS virus genome, which is comprised of RNA.

University of Rochester President Joel Seligman, with 2013 Diversity Award winners Suzanne Piotrowski (THSP), Kevin Graham (THSP), Alyssa Cannarozzo (THSP), Lynne Maquat of the Medical Center, Kim Muratore (THSP), and Vice Provost for Faculty Development & Diversity Vivian Lewis.

Lynne Maquat, Ph.D., J. Lowell Orbison Endowed Chair & Professor, Biochemistry & Biophysics; Director, University of Rochester Center for RNA Biology: From Genome to Therapeutics; Chair, University of Rochester Graduate Women in Science, has been selected to receive one of two 2013 Presidential Diversity Awards for exemplary contributions to the University's diversity and inclusion efforts. Dr. Maquat is being honored for combining her groundbreaking research agenda with a lifelong commitment to helping women succeed in science. Her remarkable accomplishments include the networking and mentoring programs she initiated as president of the RNA Society; her creation in 2003 of the University of Rochester Graduate Women in Science (GWIS) program; and her award and renewal of an NIH training grant that supports graduate students, including underrepresented minorities, in the cellular, biochemical and molecular sciences.

The Presidential Diversity Awards were created in 2009 by President Joel Seligman to recognize faculty, staff, students, units, departments or teams that demonstrate a commitment to diversity and inclusion through recruitment and retention efforts, teaching, research, multi-cultural programming, cultural competency, community outreach activities, or other initiatives.