The Michigan Daily - michigandaily.com Monday, March 19, 2012 - 5A The Michigan Daily - michigandailycomMonday, March 19, 2012 - 5A Research team analyzes impact of Hsp33 protein Findings recently published in prominent science publication By ANNA ROZENBERG Daily Staff Reporter Chaperones aren't just the awkward adults at your high- school dance, but also a type of protein that University faculty are starting to better scientifi- cally understand. Biology Prof. Ursula Jakob and a team of collaborators comprise a study that exam- ines chaperone protein Hsp33, which the team specifically investigated in bacteria. The study has been going on over the course of the past four years, and they recently had their paper published in Cell, a renowned biology journal. The function of chaperone proteins is to help other pro- teins function, and until Jakob's study, the way in which Hsp33 work in bacteria was unknown. She said the implications for studies on such proteins are cru- cially important, since all mod- ern life relies on the function of proteins to carry out basic pro- cesses in cells to survive. Jakob said when any cell in any organism encounters stress- es like a fever or viral infection, its proteins start to denature, or lose the structure that they need to function properly. "Not only do they lose activ- ity, but what's worse, they start to want to form aggregates," Jakob said. "This is very toxic for the cell. The reason it's so toxic is it's irreversible." Jakob said this conglomera- tion is similar to an egg boil- ing, beginning in a liquid form before turning solid through the boiling process. Jakob and her team discovered how Hsp33 prevents protein inside bacte- ria cells from hardening when under attack by stressors, spe- cifically bleach. "This is important because we produce bleach in our body," Jakob said. "Our white blood cells produce bleach to kill off bacteria." Jakob and her team found that when bleach activates Hsp33, it actually unfolds, los- ing some of its structure before interacting with other proteins. "In contrast to all the other proteins which unfold and lose their function, Hsp33 needs this unfolding to gain its func- tion," Jakob said. "This is very contrary to what has been in the textbooks for many, many years." Until this study, it was a well- known theory that proteins lose function when they lose their structure, according to Jakob. However, because Hsp33 does the opposite, the new find- ings seem to be a revolutionary exception to the rule, she said. "(Hsp33) uses the flexibility it gets because it loses part of its structure to really embrace and mold itself around other proteins that are unfolding and thus preventing them from interacting with other unfold- ing proteins and forming those aggregates," Jakob said. Jakob explained that the sec- ond part of the study involved discovering what happens once the stressor is gone, and how the partially unfolded proteins regain their structure so they can again perform functions required for the bacteria to live. "Ideally, the client needs to gain back its structure to func- tion again, because we want to survive the stress condition, not just endure it," Jakob said. Jakob and her team found that when the stressful condi- tions dissipate, Hsp33 pulls the client protein farther apart. This conformational change allows the client protein to be available for another class of chaperone proteins that will refold them to their active state, according to Jakob. "In general, it's a mechanism for how bacteria defend them- selves against stress - stress that they encounter when they invade us," Jakob said. "It's a very clever strategy these bac- teria have developed because it's so instantaneous." Though chaperone proteins like Hsp33 are found mainly in bacteria, they also appear in some unicellular, eukaryotic parasites like Trypanosoma that causes sleeping sickness, Jakob said. Ultimately, she said her team hopes to use their findings for drug design against such diseases. "If we understand how they defend themselves, we can understand how to attack them better," she said. Dana Reichmann, research fellow in the Department of Biology and another author of the paper, further explained the significance of the discoveries regarding Hsp33. "We knew it's important for bacteria, but we didn't really know the mechanism for the protection," Reichmann said. Reichmann said Hsp33 acts like Play-Doh in its flexibility, binding to the proteins at risk from stress in order to protect them. "There is really nice struc- tural interplay with the chaper- ones and the substrate ... They affect the conformation of each other which enables further release of the protein," Reich- mann said. Reichmann also highlighted that before their research, it was unclear how Hsp33 acted without any added Adenyl tri- phosphate energy - the prima- ry energy source produced and used by the human body. "It's really one of the first chaperones which are not ATP-dependent chaperones," Reichmann said. "Up to now, it was unclear how these types of chaperones were working ... it brings another mechanism to different types of chaperones, not necessarily the ones we know." Reichmann said there are homologous proteins found in plants, and more studies relat- ing to Hsp33 and similar chap- erone proteins are in the works, noting that this study is just the beginning. "To look at chaperones and parasites and look at how we can target them ... this will be MATCH DAY From Page1A ebrate the hard work and success of the students. "As a faculty member, we take great pride in the opportunity to mold and help launch the careers in medicine of these talented young men and women," Wool- liscroft said. A ceremony filled with mixed emotions of joy, relief and hys- teria followed the lunch ban- quet during which each student shared their placement on stage. Rajesh Mangrulkar, associate dean for medical student educa- tion, said he finds it very exciting to see students embark on the next stage of their professional career. "It's also a day that many of our students choose to share with those who have supported them - their family, friends, and our faculty and staff," Man- grulkar said. "So Match Day feels like a community comingtogeth- er to celebrate this important step for them." Mangrulkar said when he was a medical student, Match Day was a mixture of relief, nervous anticipation and exuberance. "For the first time, they will be practicing physicians in the field they have chosen - and nowthey know where that will be," Man- grulkar said. Mangrulkar added that the day was very dramatic for many of the students who will be mov- ing to a brand new city with a new medical culture. "Imagine not knowing where you are going to live one minute, and then opening up an envelope and knowing exactly where you have to live," Mangrulkar said. Mangrulkar reminded stu- dents that the profession will provide numerous challenges in theirthree to sevenyear residen- cy placements. "Our patients really need change agents to go out and improve their health, through clinical care, research and edu- cation," Mangrulkar said. "Build on your wonderful foundation from U-M, and never forget why you went into medicine in the first place." Medical student Hela Issaq, who received the Harold Kes- sler, M.D. Scholarship award in December 2011 for her commit- ment to the principles of fam- ily medicine, said she is thrilled about receiving residency train- ing in the Department of Fam- ily Medicine at Harbor-UCLA in Harbor City, CA. "I was emotional because I had thought about this day for the past four years and it was finally here," Issaq said. "I knew that I wanted to do family medi- cine even before I started medi- cal school and my dream was coming true." Issaq added that she is also elated to be the first female Afghan-American medical stu- dent to graduate from the Uni- versity's medical school. Medical student Ian May said in some respects, the name of the hospital placed inside the small white envelope represents the sum of an individual's medical achievements thus far. "I had a jumble of feelings, excitement, foreboding, ner- vousness all rolled into one," May said. "In hindsight, it seems a little strange that such a thing could produce such a combina- tion of anxiety and elation." May will spend his residency training for emergency medicine at Madigan Army Medical Cen- ter in Tacoma, Wash. A tradition of the University's Match Day includes students using pins to pinpoint their placement site on a map of the United States. Medical student Eric Tannen- baumplacedhispinonAnnArbor as his residence in orthopedic surgery will be at the University of Michigan Health System. "My first choice was Michi- gan. When I opened the envelope and got Michigan as my match, it felt as ifa 50 pound weight was lifted off my chest," Tannen- baum said. He added that he was nervous about where he and his fiancae would be spending their lives for the next five years. Upon discov- ering he was placed in Ann Arbor, he said it was the first moment he was able to truly relax as a medi- cal student. While29 percentofgraduating students will remain at the Uni- versity for their residency, other graduates were placed at institu- tions in 22 states acrossthe coun- try, including Washington D.C., California and New York, accord- ingto a UMHS release. The release also indicated that 99 percent of graduating medi- cal students were able to obtain a placementthis year, puttingthe University 5 percent above the national average. The placements were deter- mined by the National Resident Matching Program, a not-for- profit corporation thatuses auni- formed process to place 16,000 medical students at residency sites each year. Each placement site submits a list of applicants in the order of preference and each appli- cant will also rank his or her site preferences. Then, a computer program will compare the lists against each other and deter- mine the most appropriate place- ment. FOLLOW THE DAILY ON TWITTER @MIC H IGANDAILY one of tne nest in tne nation. Every year, U-M students form S the largest share of our entering Doctor of Pharmacy (PharmD) class. Their undergraduate majors range from biology and chemistry to psy- chology and anthropology; international studies and sociology to English and engineering. 25 Years Back, 25 Years Forward: Environmental Law At The Crossroads March 23-24, 2012 University of Michigan Law School, Hutchins and South Hall, Ann Arbor, MI KEYNOTE SPEAKER Friday, March 23, 12:45 P.M. Bob Perciasepe Deputy Administrator, U.S. Environmental Protection Agency FEATURED SPEAKERS Friday, March 23, 9:00 A.M. Richard Lazarus Howard and Katherine Abel Professor of Law, Harvard Law School Saturday, March 24, 12:00 P.M. John Cruden