Table of Contents

From the chair ...... 3 Department Around the World ...... 20 New Biochemistry Building ...... 4 Department Alumnus: David Bernstein ...... 21 Our Department in Uganda ...... 5 Computational Approach to Great Lakes Bioenergy Research Center ...... 6-7 Molecular Interactions ...... 22-23 Honors and Awards ...... 8-9 Remembering Helmut Beinert ...... 24-25 Perry Frey Retires ...... 10-12 In Memoriam ...... 25 Staff Departures ...... 12-13 Our Department in India ...... 26-29 A Simple Approach to Biochemistry Graduate Degrees ...... 30-31 Understanding Stem Cells ...... 14-15 Department Alumnus: Jason Gestwicki ...... 32 IBiP at 2 Years ...... 16 From the Labs ...... 33-49 Student Faculty Liaison Committee ...... 17 Contact Information ...... 50 Book and Journal Covers ...... 18-20 Donors ...... 51

The B1118 auditorium, 1985 tower and 1956 wing. The auditorium and 1956 wing will be removed to make way for the Phase II Biochemistry building. (See page 4)

If you would like to learn more about the exciting new building project, please feel free to contact: Elizabeth Craig, Chair Marilyn Boland, Director of Development Department of Biochemistry or University of Wisconsin Foundation Phone: 608-262-3040 Phone: 608-890-1230 [email protected] [email protected] From the Chair by Professor Betty Craig It is my pleasure to bring you greetings Phase II Building Project, last year saying from the Biochemistry Department for the "I hope when I write you a year from now I year 2008. As I write this dispatch, the last can report that we have broken ground…". piece of the newsletter, which Marv Wick- Th e news this year is – almost. By the end ens and his collaborators have put together of the summer demolition of the 1956 for you, there are true hints of spring – very wing (and the animal quarters and audi- welcome after a winter, the likes of which torium built in 1985) should commence, Madison has not seen in years. Th e pages with ground-breaking in early fall. We are that follow bring you not only the year’s keeping our fi ngers crossed and scurrying "news" from the department, but also slices around to temporarily relocate those to be of the exciting science going on in our labs. displaced by the construction - animals to Here is a preview of a bit of what you will the Biotron, the BMRB computer group fi nd inside. to the library in the Biochemistry Addition For decades the department has had and seminars and teaching labs to the new an international presence, training many Microbiology building. On page 4 Mike students and hosting many scholars from Cox provides a more expansive description abroad in individual laboratories. In the past of our exciting project. few years the character of our international Faculty comings and goings: As noted in endeavors have begun to change, taking on last year’s newsletter, Bill Reznikoff packed a broader perspective, thanks to the eff orts up his lab and moved to Wood’s Hole Bio- of two faculty in particular. An update of the logical Labs last July. Perry Frey, who retired program "Uganda Study Abroad: Interna- at the end of the year (see page 10), is stay- tional Health and Nutrition", initiated and ing closer to home. You can still fi nd him in run by James Ntambi can be found on page his offi ce in the Enzyme Institute Building. 5. He is "on sabbatical" this spring semester Within the next year, two faculty will join and we look forward to hearing the latest on our ranks: John Ralph, a long-time Madi- his work in Uganda when he returns. In the son resident will make the switch from the fl edgling stage a year ago, but moving rap- US Dairy Forage Research Center to Bio- idly forward, is an exchange program with chemistry, making his home in the Enzyme India, the brainchild of Aseem Ansari (see Institute. John will be heavily involved in page 26). Dr. Har Gobind Khorana, who research in bioenergy, interfacing with the won the Nobel Prize in 1968 for his work Great Lakes Bioenergy Research Center at the interface of chemistry and biology (see page 6). I am also pleased to tell you while a faculty member in the Biochemis- that in the fall Alessandro Senes will join us try Department and Enzyme Institute, has as an Assistant Professor. Coming from his lent his name to the program, now offi - postdoc position at the University of Penn- cially the "Khorana Program for Scientifi c sylvania, Alessandro will set up a research Exchange". Last summer three students program concentrating on the structure of spent 10 weeks in labs on campus; hope- membrane proteins, using computational fully they are the fi rst of many exchanges, and biophysical tools. which will also include Wisconsin students I hope you have had an enjoyable and and faculty visiting and working in labs in productive year. We would be pleased to India. hear from you anytime. Visit us when you Closer to home: In my past two dis- can, to meet with old friends and to see patches I have mentioned the Biochemistry what’s new in Biochemistry for yourself.

3 New building set to break ground by Professor Mike Cox Th e site includes the footprints of all the older wings, as well as the Agricultural Journalism build- ing. Pressure from many quarters in the state and university administrations (and including many faculty in the Biochemistry Department) quickly led to the shelving of any plan that envisioned the razing of any of the older buildings on the west side of Henry Mall. Th is called for some creativity, and the Flad architects have not disappointed. Th us, the 1956 wing is now scheduled for demolition, along with the portion of the 1912 wing that connects the Henry Mall rectangle to the 1937 wing. Th e auditorium and animal rooms in the 1985 wing will also be demolished. A new Phase II Biochemistry. This view is from the "Elmer" Th e department is building again. With the state research tower will rise on a footprint south of and (the elm tree) courtyard. and the Wisconsin Alumni Research Foundation adjacent to the 1985 tower, with a footprint that contributing most of the funding, the older part includes the northern part of the 1956 wing, as of the Biochemistry complex is about to be trans- well as the current 1985 auditorium and animal formed. rooms. With six fl oors above ground, this tower Readers may remember that the department will rise higher than the current 1985 tower. largely abandoned the old 1912, 1937, and 1956 Th e research space will be connected on its east wings when it occupied the new Biochemistry addi- side with a gutted and refurbished Ag Journal- tion in 1998. Th e older wings have been occupied ism building, which will now house a variety of by several temporary tenants, including the Bacte- Biochemistry support facilities and a café. A new riology department. With the recent completion of pedestrian corridor will separate this facility from the new Microbiology building, the older Biochem- the 1912/37 wings, and will provide easy access istry wings are being vacated again and we are ready to the Elm tree courtyard from Henry Mall. Th e for Biochemistry phase II. 1912/37 wings will be transformed into modern Planning has been complex. Th e program teaching and administrative facilities. includes research facilities, teaching facilities, ser- It is an ambitious project, with many features vice facilities, and an animal care suite, with the that will enhance both teaching and research for entire project encompassing 265,000 gross square many decades to come. Demolition is to begin feet. Th e research labs are designed to house the in late summer of 2008, with ground-breaking faculty from the Enzyme Institute, as well as sev- to occur in early fall. Completion and occupancy eral other Biochemistry faculty and the entire slated for early 2011. Henry Mall will again be a Biomolecular Chemistry Department. Th e teach- staging area for the construction teams. Hopefully, ing facility will include two large modern lecture this landmark will be left undisturbed for awhile halls, many smaller teaching rooms, new teaching after we are fi nished. Expect regular updates as the laboratories, administrative space for student ser- construction moves into high gear next year. vices, and a student lounge.

Phase II Biochemistry. This view is from Henry Mall. 4 The Department in Uganda Since Fall of 2002, Professor James Ntambi has led eff ective way of obtaining clean drinking water. Current an extraordinary and invaluable program for under- groups are now involved in helping to solve the water graduates, taking them to Uganda to both learn about problem by building BioSand Water fi lters, which are nutrition and put what they learn into practice – an cheaper than tanks and are used at the household level. experience that brings new meaning to their education. Water collected from their current sources is poured Th e program combines a semester course with a through the fi lter and comes out pathogen-free. Th e 3-week fi eld experience in Uganda. During the fall students in the program do all this because they believe course, Professor Ntambi provides students with back- that in order to improve human health, good nutrition ground information on the economics and health issues practices and clean water go hand in hand. particular to Uganda, so that when students arrive they Not surprisingly, the program has a powerful ripple have a good grasp of the realities faced by Ugandans as eff ect, with valuable consequences long after the stu- they make their health and nutrition decisions. Students dents’ Ugandan experience. For most students, the pro- come to realize that necessities that many of us take for gram is their fi rst exposure to the importance of public granted, such as clean drinking water, food, education, health. Many then go on to attend elite Public Health and fi nancial resources, present daily struggles for the programs across the US that include University of majority of Ugandan citizens. Michigan, Johns Hopkins, Tufts, George Washington A common water source University, the University of Minnesota and our own UW-Madison program. Th ere are also currently 12 students in diff erent medical schools across the US and most of the others continuing their studies in graduate programs. By exposing students to critical health issues, Professor Ntambi provides students with opportunities to learn more about themselves as future health care professionals. Please take a moment and visit the program's web- site: http://www.villagehealthproject.org to learn more about what Dr. Ntambi and his students are doing and have done in the past. If you would like to make a donation to this program, please send it to: Village Health Project, 239 Red Gym, 716 Langdon Street, Th e success of the program is refl ected in what the stu- Madison, WI 53706. dents do when they return. A key example is the creation James Ntambi (right) with Paul Kimera, a civil engineer at of the student organization called the Village Health Makerer University, who helps produce the BioSand water Project (VHP). Th e goals of this project are to support fi lters thay are standing next to. health and nutrition projects in developing countries and to increase awareness about international health issues on the UW-Madison campus and beyond. So far, Village Health Project has supported the building of 28 rainwater tanks in Uganda. Th ese tanks are a simple, Workshop participants learn how to test their water

5 The Great Lakes Bioenergy Research Center by Professor Rick Amasino

Great Lakes Bioenergy Research Center

Th is past fall, the Department of Energy (DOE) corn grain contains only a fraction of the energy awarded one of three nationwide Bioenergy that is captured by the plant; most of the energy Research Centers to the University of Wisconsin- is sequestered in the cell walls of the “body” of the Madison. Our center is known as Th e Great Lakes plant. For bioenergy to have the greatest impact on Bioenergy Research Center (GLBRC; www.great- reducing CO2 emissions and dependence on fossil lakesbioenergy.org); the GLBRC is a close part- fuels, it will be critical to 1) grow biofuel crops nership with Michigan State University, and other that are less energy intensive to produce than cur- partners in the center so far include Pacifi c North- rent corn varieties and 2) convert most of the fi xed west National Laboratory, Oak Ridge National carbon in the plant into biofuels, rather than just Laboratory, Illinois State University, Iowa State the carbon in the seeds. University, and Lucigen Corporation. Th e centers Perennial grasses are an example of a type of will receive $125 million in total costs over 5 years, biofuel crop that would be less energy intensive to and the goal of all of the centers is to perform produce than corn. (Switchgrass is one example research that may facilitate the production of trans- of a perennial grass often mentioned in the press portation fuels from biomass. Several faculty from or political speeches). Once established, a fi eld of Biochemistry participate in the GLBRC including perennial grass can be harvested year after year at Bob Landick, Brian Fox, George Phillips, Mike the end of each growing season; it does not need Sussman, John Markley, Laura Kiessling, Ron to be replanted for the next season. Also at the end Raines, Sebastian Bednarek, Rick Amasino, of each growing season, perennial grasses recycle Betty Craig, Aseem Ansari and Julie Mitchell. most of their nutrients into below ground parts Before discussing the activities of our center, of the plant to be used to support next season’s I will provide some background. At present, most growth; thus, such plants require fewer inputs such of the so-called biofuel used in the U.S. is etha- as fertilizer (fertilizer production and distribution nol derived from corn grain. Th e reason for this is is quite energy intensive) and do not require culti- simple: corn grain provides a readily fermentable vation in the spring. feedstock, and the industrial processes to produce A major issue is how to effi ciently convert the ethanol from it are well established. An issue with energy stored in plant cell walls into transportation using corn grain for biofuel production is that fuel. Plant cell walls are comprised of cellulose, most estimates indicate the amount of fossil fuel lignin, and a range of other compounds which vary used to produce corn ethanol equals or exceeds the somewhat among species. Cellulose is a polymer energy of the ethanol that is produced. Of course of glucose residues, and all of that glucose would

Amasino Ansari Bednarek Craig Fox Kiessling 6 be a great source of energy for any organism that ing effi cient technologies for converting biomass could access it. Cell walls form the body and the into biofuel. Research includes prospecting for skeleton of the plant, and thus, over evolutionary organisms that might contain novel and useful time, the acquisition of cell walls that are resistant enzymatic activities, and designing microbes that to breakdown has conferred an obvious advan- are well-suited to fermentation approaches to tage. One challenge is to discover ways to “decon- biomass conversion. In addition, the GLBRC is struct” these highly stable cell walls so that their pursuing chemical engineering approaches – the components can be converted into biofuels. identifi cation of catalysts for the direct conver- Th e GLBRC eff orts are organized into the sion of biomass-derived products into fuels. following four scientifi c areas. More details are 4) Fostering Sustainable Bioenergy Prac- provided at http://www.greatlakesbioenergy. tices. Th e GLBRC also has a group exploring the org/research. environmental and socioeconomic dimensions 1) Improving Plant Biomass. Th ere are of converting biomass to biofuel. Members of two sub-areas in improving biomass. One is to this group study how to minimize energy and increase the yield of biomass per acre in ways that chemical inputs for bioenergy crop production, minimize agricultural inputs and environmental how to reduce greenhouse gas emissions from degradation. Th e other is to modify the chemistry the biofuel production cycle, and how to predict of the biomass. For example, genetic manipula- environmental impacts of harvesting biomass tions might render plant cell walls easier to con- repeatedly in an area. Th is group also studies the vert to biofuels. Furthermore, some of our eff orts social fi nancial components that will be needed (at Michigan State University) are to evaluate to make the biofuel industry most environmen- the possibility of creating plants that accumulate tally sustainable. potential biofuel chemicals in addition to cell It is important to keep in mind that although walls, such as sugar, starch or oil – compounds biofuels may be part of the solution to our energy that could readily be used for biofuel production needs, biofuels cannot provide all that is needed. with existing technologies. (In Brazil, ethanol is A DOE report indicates that U.S.-produced cel- made from the sugar in sugarcane rather than lulosic biomass could provide a carbon-neutral from sugarcane cell walls, but sugarcane cannot source for ~30% of current U.S. transportation be grown in most of the U.S.) fuel needs by the year 2030 (http://genomics- 2) Improving Biomass Processing. How plant gtl.energy.gov/biofuels/b2bworkshop.shtml). biomass is processed is likely to play a key role in It is important to note that the transportation rendering the biomass more accessible to the con- sector accounts for ~30% of U.S. fossil fuel con- version process. Physical, chemical and enzymatic sumption. Th us, overall biomass and biofuels pre-treatments are being explored. For example, will not provide an alternative for all U.S. fossil a process involving pressure changes in the pres- fuel use. Nevertheless, biofuels are likely to be ence of ammonia is one component of this area part of a portfolio of approaches that help the (see http://pubs.acs.org/cgi-bin/abstract.cgi/ U.S. to become more energy independent and bipret/2007/23/i04/abs/bp070098m.html). more carbon neutral, and the GLBRC hopes to 3) Improving Biomass Conversion to Energy contribute to making biofuels a larger part of our Compounds. Th is key area is focused on develop- energy portfolio.

Landick Markley Mitchell Phillips Raines Sussman 7 Honors & Awards Faculty Richard Amasino – WARF Kellet Mid-Career Faculty Thomas Martin – Earl W. Sutherland Professor Research Award 2007-2012 of Biochemistry Samuel Butcher – 2007 CALS Pound Award for Julie Mitchell – Vilas Award Excellence in Research James Ntambi – Fulbright Scholar, African Regional Elizabeth Craig – American Association for the Research Program Advancement of Science Ronald Raines – American Peptide Society's Hector DeLuca – CALS Distinguished Service Award Makineni Lectureship Perry Frey – Hilldale Award; Career Leadership from Thomas Record – Fellow, American Academy of Arts American Chemical Society and Sciences Laura Kiessling – Harrison Howe Award; Fellow, National Marvin Wickens – RNA Society Service Award Academy of Science Christiane Wiese – NSF Career Grant Laura Kiessling and Ronald Raines – MIT Technology Award

Classified Staff Cheryl Adams Kadera – CALS Classified Staff Recognition Theresa Pillar – CALS Classified Staff Recognition Award Award

Graduate Students Graduate Teaching Sigrid Leirmo Excellence Award Memorial Award in Biochemistry Ed Huttlin Christopher Warren This award is intended to recognize a This award is to be given to a postdoctoral Biochemistry graduate student who has or graduate student who displays clear consistently shown evidence of quality, promise as a research scientist. The award commitment, and innovation in teaching. is to be designated in appreciation of the student’s consistent willingness to contribute to the intellectual and technical Graduate Mentoring Award potential of his or her fellow students and Ian Lewis colleagues through the selfless help of others. This award is designated to honor Bio- chemistry graduate students who consis- tently provide quality guidance and scien- tific training in mentoring undergraduate students in their research efforts.

Undergraduate Majors Mary Shine Peterson Scholarship Recipients Kimberly Clark Scholarship Recipient Siang Yun Ang Mariko Hasebe Brad Nelms Kevin Campbell Matthew Vogt Hao Li Marion A. Hicks Scholarship Recipient Jia Luo Biochem 501 Peer Mentoring Scholars Robert Erdmann Molly Lowndes Genentech Scholarship Recipients Katherine Gielissen Brad Nelms Molly Isola David Ziehr 8 Postdoctoral Fellowships Name Lab Fellowship Matthew Flowers Ntambi American Heart Assn Postdoctoral Fellow Declan James Martin American Heart Assn Postdoctoral Fellow Peizhen Yang Craig American Heart Assn Postdoctoral Fellow Enpeng Zhao Attie American Heart Assn Postdoctoral Fellow Ngan Lam Kimble Damon Runyon Fellow Takashi Higurashi Craig Human Frontier Science PD Fellow Matthew J. Allen Raines/Kiessling NIH Postdoctoral Fellowship Dana Byrd Kimble NIH Postdoctoral Fellowship Bryan Phillips Kimble NIH Postdoctoral Fellow Th omas Lee Craig NIH NRSA Postdoctoral Fellow Amy Prunuske Craig NIH NRSA Postdoctoral Fellow

Graduate Student Fellowships University Name Lab Fellowship Th omas Gisel Rayment Advanced Opportunity Fellow Khanh Ngo Cox Advanced Opportunity Fellow Juan Rodriguez-Molina Ansari Advanced Opportunity Fellow Bryan Becklund DeLuca R.H. Burris Fellow Rebecca Turcotte Raines RATH Fellow Edward Huttlin Sussman Th omsen Wisconsin Distinguished Fellow

Departmental Name Lab Fellowship Alison Meyer Craig Biochemistry Scholar Frederick Porter Palmenberg Biochemistry Scholar Tzu-Yuan (Cindy) Chao Raines MAO Wisconsin Distinguished Fellow Lori O'Brien Wiese Steenbock Fellow Graeme Garvey Rayment WARF Research Scholar

National/International Name Lab Fellowship Clayton Carlson Ansari AHA Predoctoral Fellow Justin Brumbaugh Coon NSF Fellow Amanda Johnson Amasino NSF Fellow Rex Watkins Raines NSF Fellow

9 Perry Frey Retires by Professor Brian Fox Gaining a view of the world through the lens uate studies with Prof. R.H. Abeles in January of chemistry and the molecules of life. 1964 at the University of Michigan and received For a considerable time, the involvement of free an NIH pre-doctoral fellowship to support this radicals in enzyme catalysis was curiously con- eff ort. After only a short time in Michigan, he fi ned to the realm of only a few fl avoproteins, the moved with Abeles to Brandeis University. It was cytochrome P450s, and cobalamin-dependent an outstanding opportunity at an exciting time enzymes. Likewise, the cofactor S-adenosylme- that led to the discovery of many basic principles thionine was usually considered to be a methyl of catalysis by cobalamin-dependent enzymes. group donor. However, the role of radicals in In 1965, Perry’s and Carolyn’s second daughter, enzyme catalysis has exploded in recent years, Cynthia, was born in Waltham, Massachusetts. and we can attribute much of this to Perry Frey’s After three years, his Ph.D. studies were com- leading insight and experiments. plete, and Perry began an NIH postdoctoral fel- It is a great honor to prepare this short com- lowship with Prof. F.H. Westheimer, one of the mentary, which reprises a remarkably produc- preeminent enzymologists of all time, at Harvard tive, long, and eventful career that has generated University. Th is fellowship lasted for a year, and deeper understanding of many essential bio- led to an unsolicited off er to join the faculty of chemical processes. It celebrates research thor- Chemistry at the Ohio State University. Th ere, oughly grounded in basic chemical principles, Perry rose through the ranks to Professor and and honors the deeply appreciated eff orts of Academic Vice Chair. more than ninety former graduate and postdoc- During his time at the Ohio State Univer- toral students who chose to train in research with sity, Perry began many new projects, including Perry and share in his thrill of scientifi c discovery. studies of UDP galactose-4-epimerase, pyruvate It is also noteworthy that thirty senior collabora- dehydrogenase, galactose-1-phosphate uridylyl- tors have contributed to this sustained scholarly transferase, UDP-glucose pyrophosphorylase, experience. adenylate kinase, and many other phosphotrans- Perry started out in Plain City, Ohio, a small ferases. Th is work brought the role of cofactors town about 18 miles northwest from Columbus. NAD, thiamine pyrophosphate, and pyridoxal As a boy, he delivered newspapers during World phosphate to the light. Moreover, it was during War II and earned enough to buy his fi rst bicy- this time that Perry began his decades long, cle. He made a point of reading the newspapers defi nitive work on the mechanism and stereo- and learning about warfare. Later, as a youth, he chemistry of enzymatic phosphoryl transfer by did every kind of farm labor during vacations the synthesis of isotopically labeled nucleoside from school, including working the land, plant- phosphothioates and experimental test of these ing, harvesting, and tending animals. Later, he molecules. worked for his father, a painting contractor, to support his higher education. Few know that Perry served in the US Army for two years. After this informal education in the military, his formal scientifi c education began at the Ohio State Uni- versity, where he obtained a B.S. in Chemistry. After graduation, Perry worked for the US Public Health Service as an analytical chemist in Cin- cinnati, where he published on the properties of paralytic shellfi sh poison, saxitoxin, his fi rst of now more than two hundred eighty profes- sional papers. During this time, Perry and Caro- lyn Scott met and were married in 1961. Perry’s and Carolyn’s fi rst daughter, Suzanne, was born in 1962 in Cincinnati, Ohio. Perry also attended Evening School at the U of Cincinnati during this time, where he studied Chemistry. Th e picture above shows a leaded glass window Based on the recommendation of a mentor at commemorating Perry’s work on using the iso- the Public Health Service, Perry applied for grad- topically labeled nucleoside phosphothioates to 10 elucidate the mechanism of phosphoryl transfer. enzymes and to chemical systems. In the strong His students created this art piece for his 50th Institute research environment, previous stud- birthday in 1985. Each student cut a section of ies of pyruvate dehydrogenase expanded, and glass, and the sections were fi tted and leaded by studies of another complex thiamine pyrophos- Rahda Iyengar, an Assistant Scientist in the lab phate-dependent enzyme, alpha keto glutarate at the time. Th e work shows chiral [16O, 17O, dehydrogenase were begun. Undecagold clusters 18O]thiophosphate, with each isotope of oxygen were produced and used as biochemical labeling in a diff erent style. agents, and the participation of strong hydrogen Perry and Carolyn moved to Madison and bonds in enzymatic reactions came into vogue. the University of Wisconsin in 1981. He was Likewise, the work on the clostridial enzyme recruited to join the world-renowned Insti- lysine 2,3-aminomutase began. In a prescient tute for Enzyme Research, which had begun to 1993 manuscript in FASEB Journal, Perry fi rst struggle with the retirement of leading research- queried with the title, "Lysine 2,3-aminomutase: ers. Over about a 15-year period, Perry led the Is adenosylmethionine a poor man's adenosylco- UW eff ort to establish and expand campus-wide balamin?" Now we know the extent of the poor strength in study of the structure and function man’s strategy for generation of a reactive radical of biological molecules, most notably enzymes. species in an enzyme active site: a gene family With Henry Lardy and Helmut Beinert already found in all kingdoms of life, with more than housed in the Institute, Perry was able to recruit 2400 diff erent family members at this writing. Mo Cleland from across the street in Biochemis- try and George Reed from University of Pennsyl- vania to join the Institute. Th is core strength was extended to structural studies when John Markley was recruited to the UW Biochemistry Depart- ment from Purdue University, Ivan Rayment was recruited to the Institute from the University of Arizona, Hazel Holden was recruited to the Institute and the UW Chemistry Department, and later transferred to the Biochemistry Depart- ment, and Brian Fox was recruited as a new Assistant Professor. Th us assembled, the Institute for Enzyme Research was reinvigorated as a pre- mier site in the world for collaborative studies in enzymology. One defi ning characteristic of this time in the early and mid-1990s was the shar- ing, cooperative, environment of the Institute, where students, post-doctorals, academic staff , and faculty members roamed freely, with respect- Th e fi gure above shows the active site of ful access to all of the substantial resources assem- lysine 2,3-aminomutase from the crystal structure bled to bear on problems of collective interest. solved by Bryan Lepore, Frank Ruzicka, and Perry Th ere was no corner where a receptive ear to a in Dagmar Ringe’s lab at Brandeis University. new idea in research or a helpful comment could Th e protein has a triose phosphate isomerase not be found. fold, and also revealed the locations of a site- Enzyme Institute Letterhead diff erentiated [4Fe-4S], pyridoxal phosphate, S-adenosylmethionine, and bound lysine. S-adenosylmethionine is bound to the unique iron atom in the [4Fe-4S] and has the critical 5’ carbon within - 4 Å of the 2,3-carbons of lysine, which is held into enzyme active site as a Schiff At UW, Perry and his research group contin- base with pyridoxal phosphate. Th is beautiful ued the studies of phosphoryl transfer enzymes structural study reveals the ternary complex so and exploited the power of chiral phosphothio- elegantly documented in the other biochemical ate analogs to expand the understanding to more work on the enzyme from Perry’s lab. 11 Alongside the growing appreciation and who were in his group by their own choice, and understanding of radicals in S-adenosylmethi- whose aspirations were to improve themselves onine dependent enzyme reactions, Perry and and have some fun along the way. Research and co-workers performed one of the decisive early teaching became an essentially linked continuum, experiments on the reaction mechanism of the the one always informing, shaping, and improv- diiron enzyme methane monooxygenase. Along ing the other. with the cytochrome P450s, these powerful oxi- Once I asked Perry which course he most dants were thought to react by hydrogen abstrac- liked teaching. His initial answer was all of tion, a radical process, but evidence was scant. By them, including the undergraduate introduc- using methylcyclopropanes as radical rearrange- tory courses, which included Biochemistry ment probes, they showed that 1e– and 2e– oxi- 201 Survey of Biochemistry, Biochemistry 511 dations of unactivated hydrocarbons were both Undergraduate Seminar, Biochemistry 601 Pro- possible from this enzyme reaction. Th is laid the teins and Enzyme Structure and Function, Bio- groundwork for much future experimental and chemistry 624 Mechanisms of Enzyme Action, computational analysis of the reactivity of diiron Biochemistry 625 Coenzymes and Cofactors in enzymes. Th is is an enduring characteristic of Per- Enzymology, and Biochemistry 660 Biochemi- ry’s research: early insights supported by crucial cal Techniques. However, upon refl ection, Perry experiments and extensive subsequent research stated, “my favorite course is Biochemistry 990 undertaken by Perry’s group and many others. Enzymology Research. I derived the most plea- Upon contemplation, Perry has regarded his sure teaching research to graduate students and position as a professor of Chemistry and Biochem- watching them become mature scientists. I would istry as the best job in the world for him. From his like this to come through.” But, anybody who view, nothing could have been more rewarding ever attended Biochemistry 990 would already than a career working with bright young people, know this to be true.

Departures

Two long time employees, Kay Fitzgerald and "In retirement, I hope to pick up my needle- Janice Carberry, retired this past February. work again, refresh my knitting skills, and make a Kay joined the department in 1988, and dent in all the fabric in my basement waiting to be Carol Marth – a legend in her own time – was sewn. I’ll still be playing for the St. Joseph choir, her supervisor. Kay really enjoyed both Carol and masses there and at Our Lady Queen of Peace. And her co-workers. She took a state test to upgrade hopefully, weddings will still be going on needing her work title and so for a brief time worked at an organist. Did I mention de-cluttering the base- Physical Plant, but soon found she missed the ment? So, don’t worry that I’ll be twiddling my professors and students. When the opportunity thumbs in retirement. But I will be missing my presented itself to return to Biochemistry she wonderful Biochemistry friends." jumped at it. She says: "I’d learned my lesson: Janice joined the department in 1996, after Stay in Biochemistry. Th e people here are the working at other UW-Madison positions and at best!" Over the years, Kay’s jobs varied enor- UW-Whitewater. Janice work tirelessly at han- mously, and became concentrated on payroll dling travel payments, reimbursing our grad duties of all kinds. student hosts, and the various seminars, includ- Kay now looks forward to a wide range of ing the department’s granddaddy, the Steenbock things, including travels to visit her children. Her Symposium. son, his wife, and Kay’s grandson, are all off in Janice’s husband Dennis, also a UW Montana. Her daughter, a free-lance singer, lived employee, retired around the same time that she in Germany for 11 years, was married in Italy last retired. Here is Janice’s report on her retirement year, and now is going back to Germany, so Kay plans: will be logging the frequent fl yer miles. Here’s a "Brett Favre and I have the same retirement brief description in Kay’s own words of what’s mantra. We could have continued physically, but coming: we are mentally spent. We both look forward to

12 decompressing and being a sofa-slug for a short development of our fi rst content management recovery period. During the winter cold I have system, MyBiochem. He spearheaded the depart- been enjoying reading in the sun room, snow- ment’s transition to the WiscMail email system, shoeing, chipping ice, tutoring 3 kids and attack- successfully managing one of the largest email ing those piles of "life stuff " that accumulate so migrations on campus. Michael was also the driv- quickly. We will remain in our Verona home and ing force behind the recent expansion of our fi le complete some renovation projects. Volunteer server infrastructure, helping defi ne policy com- opportunities abound and I will continue to do mitted to protecting our critical research data. part-time work close to home. Warmer weather Alas, as a conceptual artist, Michael's tenure will fi nd us biking, exploring the mid-west and in IT could not last long. Whether it was video heading north in our camper to spend more time shot in multiple camera angles, helium balloons with the three grandchildren." fi lled with light, or large, industrial wooden peg Also leaving the department are Danielle smashers, his art was fi rst. He left Biochem in Tolzmann and Michael Eckblad. September and began his newest project, "Drop Danielle has been our purchasing supervisor Everything and Run." since 2004. Danielle took a new position across We all wonder precisely what it means to be campus to Visitor & Information Programs, alive. We now can answer this question empiri- housed in the Red Gym. Her last day was in early cally: What minimal set of genes are needed to March. make a reproducing, living creature? But Michael, If you had a computer problem during the not surprisingly, has taken a diff erent tack. On last fi ve years or so, you likely talked with Michael leaving the department in September, Michael Eckblad, or possibly, his spot-on impersonation gave up all of his possessions to see where that of George W. Bush. Starting in 2002 as a student would lead, and as an off shoot, what might actu- hourly with IT, Michael happily answered your ally be required for his existence. To learn about technical questions, and maybe even told you this newest project - "Drop Everything and Run" about new bands on the horizon. He also had a - and others that inhabit his fertile and congenial knack for systems administration, and in 2004 mind, visit his website - MichaelEckblad.com was instrumental in the rollout of the "new" fi le We look forward to delineation of the minimal and email servers. Eckosome. Later on, as a full-time IT staff er, Michael’s We will miss all four of them and wish Kay infl uence continued to expand. He took charge and Janice the best in their retirements, Danielle of the new Biochem website and helped with the at her new position and Michael in his journey.

Janice Carberry (left), Kay Fizgerald (center) and Micheal Eckblad (right)

13 A simple approach to understanding stem cells by Professor Judith Kimble Stem cells have the magical ability to produce In human tissues, many stem cells exist more of themselves and to also make specialized throughout adulthood and replenish tissues that cells, such as muscle or nerve (Figure 1). Th e continuously make specialized cells (e.g. ger- capacity of stem cells to replenish tissues as they mline stem cells in the testis, hematopoietic stem get damaged, diseased or worn out holds tremen- cells in the blood, neural stem cells in the brain). dous promise for human health. But to fulfi ll that In C. elegans, only one type of stem cell persists promise, we must learn how to control stem cells throughout adulthood, and that is the germline within an organism. Many cancers are thought stsstememe cell, which replenishes sperm and oocytes to result from unleashed stem cells gone awry, ass ttheyhey araaree ususeded ffororo rreproduction.ep Germline stem and stem cells — with their virtually unlimited cecellsells araaree unuunusualnusuau l inn tthathhat thttheyeyy rretainetain ththe capacity capacity for growth — will certainly wreak havoc to crecreateatte alaalll cecellsells of aann enentiretit re oorganismrgganism when ttrig-rig- if they are not carefully controlled. gered by ferfertilizationtiilizaz tiionn aandndd tthereforeheh reefof rere aarere ttheheh ulti- mate stem cells fofforr alaallll tittissuesssues inn tthehee bbody.odo y.y OOururu work therefore focuses oonn geggermlineermmliinee sstemtet m ceccells,lll s, Stem Differentiated Cell Cells in part because they are the oonlynlly gagamemem iinn ththishisis roundworm town and in part becaubecausesee ttheirheh ir ttoti-oto i-i- popotencytency makes them particularly intereinteresting.stinng.g

Conserved molecular regulators control stem cell maintenancmaintenancee WeWe have foundfound C. eleganss stem cell regulators Figure 1: Stem cells can both self renew and generate ththatat aarere conserved in all animals and that appear diff erentated progeny to control stemm cecellslls in many diff erent biologicalbiological settings. One example is NNotchh sisignaling.gnaling. In C. My lab focuses on unraveling molecular mecha- elegans, a special regulatory cell provides a stemm nisms of stem cell regulation, and in particular, cell ‘niche’ that is essential for maintenance of analyzing those mechanisms in an organismal germline stem cells (Figure 2). Th at regulatory context. Our approach has been to use a genetic cell makes a ligand for the Notch receptor, and scalpel for the identifi cation of stem cell regu- the activated Notch receptor responds in germ lators in a relatively simple animal, the nema- cells by turning on genes critical for stem cell tode Caenorhabditis elegans. Once a regulator is maintenance. Most importantly, germline stem in hand, we then use a variety of approaches to cells are lost when Notch signaling is turned off , fi gure out how it works. Over the years, we have and germline tumors arise when Notch signaling learned that many stem cell regulators found in is left on aberrantly. In vertebrates, Notch sig- this small roundworm turn out to be broadly naling has been implicated in stem cell control, conserved for the control of stem cells through- and in particular for hematopoietic and neural out the animal kingdom, including humans. stem cells. In humans, defects in Notch signal- ing cause leukemia and have been implicated in C. elegans as an organism to study stem cells Alzheimer’s. Th erefore, our work on Notch sig- C. elegans turns out to be an extraordinary naling in the C. elegans germline has important model for basic biomedical research. Th is little implications for human health. roundworm is only one millimeter long and can be grown like E. coli on Petri dishes or in Figure 2: Germ cells begin to diff erentiate when they leave the niche liquid media, so that millions of animals can be readily obtained to purify regulatory molecules Germline stem cell for biochemical analysis. Th e complete genome within the niche sequence is known, and individual genes can be manipulated by classical mutagenesis or by the newer technique of RNA-mediated interference. Moreover, gene products can be visualized in Niche individual cells of living animals with fl uorescent cell proteins introduced via transgenes. Germ cells

14 Another example is FBF, which belongs to work provides multiple points of regulation that the PUF family of conserved RNA-binding pro- can be modulated in response to a variety of cues teins. We fi rst honed in on FBF in collabora- (e.g. nutrition, pathogenesis, aging). tion with my long-term colleague, Dr. Marvin Wickens. Using the Wickens yeast three-hybrid A novel β-catenin controls generation of the system and Kimble regulatory mutations, our niche labs together identifi ed FBF as a key regulator Th e stem cell niche is a key factor in stem cell of the sperm/oocyte decision. When FBF was control. Th us, a larger or smaller niche main- deleted fully from the genome, we found that tains more or fewer stem cells, respectively. To FBF is also essential for stem cell maintenance. understand how a niche is formed, we analyzed Remarkably, PUF RNA-binding proteins control specifi cation of the niche for germline stem cells, germline stem cells in both C. elegans and the which consists of a single regulatory cell (Figure fruitfl y Drosophila, and they have been impli- 2). We recently found that this regulatory cell is catedcated in control of germline and embryonic stem specifi ed by the Wnt signaling pathway, which cells in vertebrates,vertebrates, inincluding humans. In addi- activates target genes by a conserved DNA- tion, PUF proteins are criticalcritical foforr reregenerationg binding protein (TCF) and its transcriptional in planaria fl atworms, and perhaps function in co-activatorco called β-catenin. What is perhaps other regenerating tissues, where latent sstemtem cecellslls most excitingexciting in oour work is that Wnt signaling are activated to proliferateproliferatee aandnd rreplenisheplenish ttissue.iissue.e usesusess a nnovelovel protein that bebelongslongs to the β-catenin Th erefore, PPUFUFF proteinsprootteiins standstand ououtt as ccriticalritical rereg-eg-g familyfamimily basedbased onon both functional and structuralstructural ulatorsulatorrs of sstemtem cecellslls in vvirtuallyirrtut allyl aallll aanimals.nin mam ls. criteria.crriiterria. OurOuur structuralstrur ctural studies have been done O Onenen mmajorajor ggoaloal off ttheheh llababab hhasass bbeeneen tot fi ggureure ini collaborationcolo laborar tionn withwith the laboratory of a crystal- outouut howhoh w NotchNotch sisignalinggnaling anandnd PUPPUFF RNRNA-bindingAA-bbinding lographerlograppheh r fromfromm thethe UniversityUnin versity of Washington- proteinspprototeinsn ccontrolonntrt ol sstemtem cells,cec llss, aandnd we have made Seattle, Dr.Dr.r WenqingWene qiing Xu.Xuu. Our work also shows somesomem pprogress.ror grg esss. FForoor NNotchotch signaling, one of our that Wnt signalingsignaalil ngn usesuses s a branched pathway to fi rrsrstt fi ndsnds was that Notch directly upregulates control the ratio off itsits DNA-bindingDNANA-binding protein and FBF, a step that links the Notch and PUF stem transcriptional coactivator,coactiivaatoor,r anan insight that maymay cell controls. FBF, on the other hand, binds to prove applicable to WntWnt signalingsignala ing more broadly. specifiifi c mmessengeressenger RNAs and downregulates pro- Pathway activation drives β-catenin-ccatenin abundance duction of proteins thath t ppromoteromote diff erentiation. up and TCF abundance downdowwn to generate an In particular, FBF downregulates expressionession of activated complex that drives transcription.trannscs riptp ion. Th e MAP kinase and a battery of other diff erentia- targetget ofof thatthat complex for niche specifispeciifi cationcation is a tion regulators. Indeed, in collaboration with Dr. homeodomain transcriptionscription factor, the C.C eleganselel gag n James Th omson, also here in UW-Madison, we homolog of human Nkx2.5. have found that two human MAP kinase mRNAs are regulated by a human PUF protein, Pum2, in Lessons of stem cell control from human embryonic stem cells. Th erefore, the PUF a model organism repression of MAP kinase is broadly conserved. So why use C. elegans to study stem cell con- trol? If all the molecular regulators are conserved, A regulatory network controls the decision why not work on them in vertebrates instead? between self-renewal and diff erentiation Th e basic answer boils down to the simplicity Our work on Notch and FBF targets has and experimental power of this small nematode. revealed the framework of a regulatory network Stem cell regulation is presented in a particularly that controls germ cells to remain as stem cells simple form in C. elegans with its single-celled or embark on a path to diff erentiation. In broad niche and use of Notch signaling for stem cell strokes, Notch signaling induces expression of maintenance. By contrast, mammalian stem regulators that inhibit diff erentiation, including cell niches have not been easy to fi nd at a cellu- FBF, and therefore maintains an undiff erentiated lar level and even less easy to analyze genetically stem cell state. FBF in turn represses expression and biochemically. Moreover, C. elegans genet- of proteins that induce diff erentiation. Th e regu- ics, when combined with biochemistry, provides latory network is not simple but it is remarkably a way to delineate a stem cell regulatory network robust – any one component can be removed within a single tissue and within the context of without abolishing stem cell maintenance or the the organism. Th is simply is not yet possible in switch into diff erentiation. Moreover, the net- a vertebrate. 15 IPiB: its fi rst two years by Professor Ivan Rayment, Chair of the steering committee In 2006, the Departments of Biochemistry and because all of the graduate committees are now Biomolecular Chemistry formally merged their represented by members of both Departments. graduate programs to form the Integrated Pro- All of these committees are now under the guid- gram in Biochemistry (IPiB, www.ipib.wisc. ance of the Steering Committee. edu). Th e reasons for this change were many, Th e Steering Committee, made up of 7 fac- but foremost it permits a streamlined recruiting ulty members from both departments, oversees and admission process for prospective students. the graduate program. Graduate student issues, Combining the programs also seemed the logical such as recruiting, laboratory assignments, and thing to do since the two departments are going teaching assignments are now handled within to be close neighbors when the new Biochemis- this committee rather than each of the respec- try Phase II building is completed. tive departments. As chair of this committee, I In the fi rst year (2006), 16 students were have to admit that the organization works well admitted. Th is was a smaller class than perhaps because the individual committees have done a the faculty would have liked, but considering the fantastic job of recruiting students, guiding them changes in the curriculum and organization, it through laboratory assignments and providing was a good size to initiate the program. Th is year, direction for the forthcoming prelim examina- IPiB Research we nearly doubled our class size (31 students tions. Th e net result of their hard work is that Topics: were admitted!), which is better than anyone there are fewer faculty meetings which is a bene- could have anticipated. It is a clear indication fi t to the entire faculty, except of course for those Cell and that IPiB is off to a good start. Comments from on the Steering Committee! Developmental our students indicate they like the new program’s Th e fi nal signifi cant change in the program Biology simplifi ed admission process, and the greater is that the students can combine the social activi- number of laboratories in which to study. IPiB ties of both departments into a greater graduate Chemical students currently have around 50 laboratories to student experience. Th e net result is that there Biology rotate in during their fi rst semester! are more opportunities for the students to get Th e new program demanded a complete together and mingle. Th e academic year begins Computational examination and overhaul of the curriculum. As with the Welcome Picnic (welcoming the new Biology it turned out, the programs in Biochemistry and class), followed by a Halloween Party (check Biomolecular Chemistry were already similar so out the SFLC website for the costume contest), Enzymology that the major changes have been organizational Friday Social Hour at BMC almost every Friday, rather than thematic. Th e Charter for the new Holiday Party (which includes an ornament con- Molecular program has been approved and is offi cially in test, and new this year, a toy drive), Joint Poster Genetics place. Session that draws a huge crowd each year (is it So what are the major changes in the pro- the research or the food that draws the crowd??!!), Molecular gram? From the perspective of the students, there Student Seminar Series, and the year concludes Medicine is a new professional development and bioeth- with the SFLC (Student-Faculty Liaison Com- ics course off ered in the fi rst semester (Mike Cox mittee) election picnic. Structural and others). In addition the “Advances in Bio- Finally, those who might worry that Madi- Biology chemistry” course (Biochem 875) that had been son’s reputation for a top-ranked program in off ered in the Fall for the past four years has been biochemistry would be overshadowed by the Virology merged with Biomolecular Chemistry (710) and attention of a merger and new program name, the is now off ered in the Spring to create a new course formal degree title for those who graduate from entitled “Exploring Biochemical Functions of the IPiB will be "a doctorate in Biochemistry." I Macromolecules (Ivan Rayment/Dave Brow and think there is a good chance that the fi rst crop of others).” Th ere is also a new seminar requirement Ph.Ds from the IPiB will occur around the 100th for the third and fourth years of the program in anniversary of the fi rst graduate student from which the students will present their research to Biochemistry. I am told by Dave Nelson that the the program. Lastly, a few changes to the prelim fi rst Ph.D. in Biochemistry (from the depart- process have been made in the hopes of allow- ment of Agricultural Chemistry) was awarded in ing more feedback to the students during the 1910 to J.N. Currie who was a graduate student oral examination. As is evident, the changes have with E.B. Hart. Based on the current program I been very modest. I would say that the greatest think we can plan on another 100 years of great changes are in the organization of the program, graduate education in Biochemistry. 16 Student Faculty Liaison Committee (SFLC) by Alison Albee, Chair IPiB SFLC Th e Student Faculty Liaison Committee (SFLC) have the seminar series last year, but this year provides a mechanism for graduate student ser- Greg Ellis has done an outstanding job rejuve- vice to the department. Th e SFLC is involved nating the student seminar series for this year. in many activities. Th ere are so many graduate Th e seminar meets every other Tuesday at noon students that work hard to make SFLC success- in the Bock Labs Penthouse and we encourage ful that I can’t name them all here, but I would you to come hear about the exciting research like to mention our social chairs, Sarah Slauson your colleagues are doing. Greg Kabachinski and Marielle Gruenig, who have done a won- has done a remarkable job with the student derful job to organize some spectacular events. invited seminar speaker and has lined up speak- At our annual fall picnic, they put together the ers for the next two years! Dr. Tom Rappaport fi rst ever kickball face-off between the new and will speak in 2008 and Dr. David Allis will speak old students. It was a great idea and a lot of fun! in 2009. Th e graduate students play a critical We look forward to them continuing their social role in recruiting and this year we have Mark magic with the Halloween party and annual Marzinke and Allyson Anding heading up the holiday party at the end of the year. Samantha recruiting eff orts. I know they will do a fan- Herbst has been instrumental in organizing our tastic job and recruit another great class! Th is departmental art show and we eagerly anticipate year we are also excited to try something new for seeing more wonderful art, hearing beautiful the SFLC. We are organizing volunteer oppor- music, and watching lovely dancing again this tunities as a way to give back to the commu- year thanks to her hard work. Th e student semi- nity. Our fi rst activity will be a toy drive this nar series provides a forum for graduate students December. We are delighted to add this new and post-docs to present their research to their dimension to the SFLC and we look forward to peers. Due to lack of enthusiasm, we did not another great year!

IPiB welcoming picnic 2007 New class

IPiB welcoming picnic 2007 Upperclass kickball champs

17 From the Bookshelf Mo Cleland Phillips and George Cox Micke This book, which should serve as a text for graduate students and a The study of proteins is central to life sciences. The cover of reference for the senior investigator, provides an in-depth coverage of the book highlights the glowing structure of green fluorescent steady-state kinetics as it is used for determination of the kinetic and protein, a protein-DNA complex and an assembled virus chemical mechanisms of an enzymatic reaction. The cover art is a capsid. Artwork by Tod Romo and John Wiley press. collaboration of Paul Cook (for the structures) and the publisher. James Ntambi James Cox Nelson and Mike Dave Fatty acids, especially polyunsaturated fatty acids, regulate RNA polymerase II from yeast, bound to DNA and in the act of gene expression via interactions with multiple transcrip- transcribing it into RNA. Image created by H. Adam Steinberg using tion factors and nuclear receptors, resulting in downstream PDB ID 1I6H as modified by Seth Darst. changes in flux through metabolic pathways. Chapter by Harini Sampath and James Ntambi. Cover art by Harini Sampath. 18 From the Covers Hector DeLuca Holden Hazel The vitamin D endocrine system is pictorially shown including regula- Glucose-1-phosphate uridylyltransferase catalyzes the formation of tors and structures. The illustration, by H. Adam Steinberg, introduced UDP-glucose from glucose-1-phosphate and UTP. Artwork by Hazel an issue of ABB devoted to current vitamin D research. Holden and H. Adam Steinberg. Laura Kiessling Laura Bob Landick Traditional anticancer targeting strategies rely on high-affinity inter- Transcriptional pausing by RNA polymerase (RNAP) regulates tran- action to recognize tumor over normal cells. In contrast, Carlson et al. script elongation. Toulokhonov /et al.,/ report rearrangements of the describe a new strategy that takes advantage of low-affinity, multiva- RNAP active site upon formation of an initially paused transcription lent interactions to target a cell for destruction by the immune system. complex, featuring a trigger-loop conformation positioned near the Cover image courtesy of H. Adam Steinberg. Cover designed by RNA 3' nucleotide, which frays away from the DNA template. Art- Theresa M. Dubé. work by H. Adam Steinberg, Jinwei Zhang, and Robert Landick. 19 The Department Around the World

Each pin represents one faculty member's involvement in that country, either through a collaboration, a meeting, teaching (or, in a few cases, something else entirely). We only allowed one type of pin per country, no matter how many PIs had contacts there. You can see instantly that Europe is a densely perforated pin cushion; but the map also makes clear that the department reaches out to every other continent as well. Which lab will be the fi rst in Solomon Islands?

From the Covers cont. Ron Raines Doug Weibel “Arginine grafting”– installing a patch of arginine residues – enhances 'Nanoart', by Tom Wilson, based on an image from the Weibel Lab the toxicity of a ribonuclease for human erythroleukemia cells. The of microstructured polymers. The image consists of rectangular arrays image depicts electrostatic potential maps of bovine pancreatic ribo- of tens of thousands of micron-scale structures for manipulating bac- nuclease (RNase A) and a model of its E49R/D53R variant (dark gray terial cells that are embossed in the surface of a polymer and make it = cationic; medium gray = anionic). Artwork by Stephen M. Fuchs. possible to confine and study bacterial physiology. The dimensions of the structures are on the wavelength of visible light, which gives each rectangle a unique color. 20 Department of Biochemistry Alumnus Dr. David Bernstein, Senior Science Policy Analyst, American Association for Cancer Research In the Wickens Lab of the hockey Warthogs’ two intramural After rotating through (and helping championship seasons (the Warthogs are the move) half the 3d fl oor labs in Biochemistry Chemistry and Biochemistry departments’ during fall of 1998, David Bernstein settled unoffi cial ice hockey ambassadors). Dave in with the Wickens lab. He had come with also spent a good deal of time debating a BA in Biochemistry from Clark University, the fi ner points of democracy with the and was ready to surprise and impress his lab’s resident communist, Labib Rouhana. new advisor. Unfortunately, that fi rst surprise Th ese and other discussions helped redirect came in Group Meeting, with an impressively Bernstein’s career. overpriced set of oligonucleotides that led to apoplexy in his mentor. Dr. Bernstein Goes to Washington Th is early oligonucleotidyl indulgence Inspired not only by Labib, but also by foreshadowed Dave’s later career. Early work he had done in Senator Kohl’s offi ce, on, Dave began studying the interaction Dave became intrigued with science policy. Dave as the Warthog's goalie of a translational regulator, FBF, with its From the biennial Biosciences Career Day, he mRNA targets. Hundreds of oligos and learned of AAAS Congressional Fellowships, mutations later, he deciphered a consensus which enable Ph.D. level scientists, doctors binding sequence that predicted new targets and engineers to hold staff positions in the of regulation. Bernstein collaborated with US Congress. Bernstein applied and was many in the Wickens and Kimble labs, awarded one for 2005-2006, and spent ending up with fi ve research papers and four that year working for Senator Kennedy’s reviews in journals running the gamut from Health Offi ce. He dealt with many technical Nature to Promega Notes. Th ese attest not issues, but focused on the Pandemic and All only to Dave’s skills and smarts, but also to Hazards Preparedness Act of 2006. His UW his willingness to work freely and generously training prepared him for the cornucopia with others. of activities, everything from lab safety to pathogen detection methods. Topics closer Outside the lab to home were surprisingly common, like the Bernstein spent what was likely too much intricacies of a new PCR technique or trying time away from the bench while at UW. He to describe RNAi the morning of the Nobel was the second head of the Student Faculty Prize announcement. Dave was impressed Liaison Committee, and a superb goalie Dr. Bernstein goes to Washington, D.C. by the infl uence a small group of staff ers could have on policy, and found the entire experience exhilarating and exhausting.

Life Outside the Bubble In late 2006, Bernstein left frenetic Capitol Hill, and now is a Senior Science Policy Analyst for the American Association for Cancer Research. Bernstein was the fi rst hire for the new AACR offi ce in Washington, DC and is helping expand their government relations activities. Much of his time is spent trying to convince Congress to spend more on NIH research, and convince researchers that it’s hard for Congress to spend more, even though there seems to be a lot of money for other things. But it’s working on the bills that supports research, fosters innovation, and speeds drug discovery – the bills that draw on the scientifi c and political worlds – that are the most fun, and the most rewarding. 21 Computational approaches to studying molecular interactions by Professor Julie Mitchell Molecular interactions provide the essential lan- of them have the ability to distinguish hot spots guage of biochemistry, and networks of such from other interface residues. interactions control physiological communica- To maximize the predictive capabilities of tion processes. It is natural to examine interac- the model, statistical methods were applied to a tions in terms of the individual behaviors, which data set consisting of binding energetics data for are largely dictated by structural features and alanine substitutions within protein interfaces of random fl uctuation. Because kinetic rates can known structure. Th e result is a model able to pre- be altered by environmental conditions such dict when substitution to alanine is likely to cause as temperature, and the basis for this is largely a binding free energy increase of at least 2 kcal/ structural, the system-wide behavior is intimately mol. We have also used the model to predict when tied to structural detail. Our goal is to use math- other types of sidechain substitutions will enhance ematical models to explore both structural and or inhibit binding. Figure 1 shows the Smad4- systems characterizations of protein association, Ski interface along with white and black spheres and we hope to develop models that address bio- that indicate favorable and unfavorable regions of logical phenomena across scales. the binding interface. Such information is useful toward selecting mutations that can enhance or Predicting Molecular Interactions inhibit binding affi nity in this system. A fundamental question in biochemistry is Our hot spot model is computationally very how the structure of molecules determines their effi cient and scalable. Most systems can be ana- function. Predicting or determining a protein's lyzed within a minute or two, and the entire E. three-dimensional fold is one piece of the puzzle. coli 50S ribosome can be analyzed in under 15 Given structures for a pair of interacting proteins, minutes. To make our computational tools most the next question is how they bind one another. useful to bench scientists, we have created a server Th is is just as complex as predicting a protein to help researchers analyze hot spots within pro- fold, though many fewer structures have been tein systems of interest. Using Jmol, we created an determined experimentally, and we have yet to interactive display with which hot spot residues fi nd an equivalent to the fold classifi cations and can be explored. Our server (http://www.mitch- homology-based approaches that have proven ell-lab.org/kfc) is now available, and a more fully successful in folding. featured interface is in its fi nal testing stages. Our approach to predicting the structure of molecular complexes is based in mathematics and physics. We have developed an energy func- tion that can distinguish native binding confi gu- rations from non-native ones. Th is is coupled to numerical methods for fi nding the global mini- mum of this energy function. Future work will explore what is a continued stumbling block in protein docking -- protein fl exibility. We are presently exploring new ways to represent proteins mathematically and to char- acterize their fl exibility using only a few param- eters that are naturally suited to optimization.

Hot Spots and Binding Energetics Some sidechains make a large energetic con- tribution to binding, and these residues can be more sensitive to substitution by another amino acid. We combined biochemical and geometric considerations, such as hydrophobicity or precise Figure 1: The Smad4-Ski interface is shown with shape match, to predict these ``hot spots.'' Vari- favorable and unfavorable regions of the interface ous features were analyzed to determine which marked using white and black spheres, respectively.

22 Optimizing Biological Systems trends were comparable between the two empiri- Changes in rate constants can have system- cal models (Michaelis-Menten and Generalized wide eff ects. Th ough much of our group's research Mass Action), and the conclusions suggest spe- involves structural biology, we are interested to cifi c bioreactor designs that we hope to test in apply optimization tools more generally toward collaboration with chemical engineers. problems in systems biology. We have recently completed two projects in this area, which are related to bioenergy and remediation. Using metabolomics data derived from NMR or other sources, it is possible to fi t time- dependent models to observed metabolite con- centrations. Because kinetic models may include nonlinear relationships between metabolite con- centrations, this can be nontrivial. We have used models with diff erent functional forms, such as Michaelis-Menten and Generalized Mass Action, as there is no established gold standard for the form of models fi t to in vivo concentrations. Once these empirical models have been obtained, they can be used to make conjectures about the possible eff ects of increasing the con- centration of a given metabolite or the rate of a particular reaction. One of our projects examined the rates of converting uranium from soluble to insoluble forms by species of Shewanella. In par- Figure 2: The glycolysis pathway in L. lactis has a ticular, examined the reaction rates for this con- branched path between pyruvate and ethanol. Only version in the presence of iron species and other one branch produces CO2. metals. Th is is due to the fact that in situ rates for contaminated soil can diff er considerably from High Performance Computing those observed in the laboratory. Th e ability to Th e computing costs encountered in biol- predict reaction rates in the presence of varied ogy can be considerable. In the past, we have types of metals can help environmental biologists addressed these needs using large supercomput- better plan cleanup eff orts at remediation sites. ers and clusters of machines. However, we are A second project examined the selectivity of presently working on some exciting new inno- glucose to ethanol conversion, with the goal of vations. Modern graphics cards can perform minimizing CO2 generation. In some organisms, many of the types of calculations required by there is a 1:1 ratio between the number of ethanol our software, and these graphics processing units molecules and CO2 molecules created, whereas (GPU's) can perform up to 128 calculations at in other organisms there are alternate branches once. By combining a number of cards within within the glycolysis pathway that do not lead to a single machine, a low-cost and space effi cient CO2 release. In addition, some organisms have supercomputer can be created. the ability to convert CO2 into commodities, Our fi rst endeavor has been to adapt our des- such as biodegradable plastic. Th is leads to inter- olvation model for this hardware. Based on use esting questions in design and optimization for of clear design principles, we are able to achieve biology-based industrial engineering. a speedup of more than 100 when using two Our initial examination of glycolysis studied graphics cards. Th us, we are already seeing the data from L. lactis to predict conditions under benefi ts of developing for this emerging comput- which the bacteria would selectively produce ing framework. In the future, we will adapt our ethanol over acetate, and for which the ratio of computationally expensive docking prediction ethanol to CO2 production was maximized. Th e codes to utilize this new technology. 23 Remembering Helmut Beinert by Professors George Reed, Brian Fox, Henry Lardy and Tricia Kiley College of Wisconsin in Milwaukee where he remained until returning to Madison in 1994. He remained actively engaged in research and scholarly activities, and his passion for science continued until his death. Dr. Beinert leaves a remarkable record of con- tributions and accomplishments in biochemistry and biophysics. His name is always associated with the field of iron-sulfur proteins, although he was adamant in pointing out that he was not the original discoverer of this class of proteins. Rather, he was the leading figure in characterizing the electronic structures and functions of many members of this large family of metalloproteins. Dr. Beinert was an early proponent of the use of electron paramagnetic resonance (EPR) spec- troscopy to study paramagnetic intermediates in flavoproteins as well as metalloproteins such as the iron-sulfur proteins. His collaborative EPR experiments in the 1960’s wherein 57Fe and 33S Professor Emeritus Helmut Beinert died on and subsequently 77Se were incorporated into December 21, 2007, at the age of 94. He was iron-sulfur proteins revealed the covalent nature born Nov. 17, 1913, in Lahr, Germany. He of the iron-chalcogen core were classic achieve- received a bachelor’s education in the classical ments. Dr. Beinert’s work on fatty acid oxidation traditions of Latin, Mathematics, Greek and and tissue respiration led to many important dis- French, along with some Chemistry and Physics. coveries including an abundance of iron-sulfur He then studied acting at the State Theater and centers in proteins of the respiratory chain of became a professional actor prior to being drafted mitochondria. The discovery of an iron sulfur into the army. Helmut asked for and was granted cluster in the tricarboxylic acid cycle enzyme, a leave to pursue graduate studies in Chemistry aconitase, expanded the repertoire of iron-sulfur at the Universities of Leipzig and Heidelberg. His clusters beyond electron carriers to catalysts. thesis work, completed in 1943, was carried out at Kaiser-Wilhelm Institute for Medical Research e– in Heidelberg. Dr. Beinert was careful to avoid 3+ 3+ research that would stimulate any interest from Fe Fe the military, and surviving the turmoil of the e– war years was something that he attributed to S = 0 S = 1/2 the good fortune of simply being born in 1913 2+ 1+ instead of 1914. e– After the war, the Control Commission S = 0 S = 9/2 of the Allied Forces moved a group of medical 2+ 1+ doctors and chemists to Randolf Field in Texas, where Dr. Beinert carried out studies of the fate e– of exogenously administered cytochrome c in tis- sues. In 1950, Dr. Beinert came to the Institute S = 1/2 S = 2 for Enzyme Research to carry out postdoctoral 1+ 0 work. One of his early projects was to develop a new method for the isolation of coenzyme A. e– e– Dr. Beinert was promoted to professorial rank in 1952 and became a full professor in 1962. S = 1/2 S = 0 S = 1/2 He retired from the University of Wisconsin in 3+ 2+ 1+ 1984 and took a professorship at the Medical Localization and delocalization patterns in Fe-S clusters

24 Subsequently, Dr. Beinert participated in reveal- a lifetime NIH Career Development Award. He ing the roles of iron-sulfur clusters in transcrip- was elected a member of the US National Acad- tional and translational regulation. Dr. Beinert’s emy of Sciences in 1980. Dr. Beinert’s numerous scientific contributions span a period of more awards included the Keilin Medal of the British than 60 years. Biochemical Society, the Sir Hans Krebs Medal Dr. Beinert’s accomplishments were recog- of the European Biochemical Societies, the Fritz nized internationally. He was respected as a pio- Lipmann Award from the American Society of neer in the areas of bioinorganic chemistry and Biochemistry and Molecular Biology, the Otto biophysical spectroscopy. He was a recipient of Warburg Medal of the German Society for Bio- chemistry, and Honorary Doctorates of Science Ray Hansen and Helmut Beinert conducting an EPR experiment from the University of Wisconsin-Milwaukee and the University of Konstanz. For the last several years Dr. Beinert main- tained a quiet presence at seminars and sym- posia around the campus. His early morning trips to the Steenbock Library equipped with his briefcase, dark glasses, and flat cap were a familiar and comforting sight. Dr. Beinert was popular with students and postdoctoral fellows who benefited from his encyclopedic knowledge of biochemistry and his willingness to share his perspective on science. Dr. Beinert had many collaborators here at UW and around the world. Many of these projects established new areas of investigation that provide a continuing legacy for Dr. Beinert. His sharp wit, remarkable intel- lect, exceptional standards, and indomitable spirit will be sorely missed.

In Memoriam

Beinert, Helmut Morris, Mark Jr. Savage, Jane Ramsdell (Professor 1967-1984 and (worked in PH Phillips lab, (MS 1963, Harper) Emeritus Professor 1994-2007) PhD Vet Science 1962-63 June 5, 2002 December 21, 2007 January 14, 2007 Th orne, Curtis Colovos, George Charles Ogilvie, Marvin Lee (MS 1944 Peterson, (MS 1943, Johnson) (MS 1959 Hoekstra, PhD 1948 Peterson) 2006 PhD 1962 Hoekstra) January 10, 2008 February 1, 2008 Frea, James Irving Weaver, Robert (PhD 1963, Strong) Quackenbush, Forrest Ward (Post Doc 1958-60 Lardy) November 28, 2005 (MS 1935, Peterson February 13, 2008 PhD 1937, Steenbock) Marsh, Eloise Margueritte May 21, 2007 (Dept. Secretary 1955-1982) April 22, 2007

25 The Department, the University and India: Khorana Exchange Program by Professor Aseem Ansari Dear Sir/Madam, I have read about your very exciting research on the website and am seeking the privilege of working in your esteemed laboratory, under your excellent guidance…. or so went the request from a faceless, eager, and potentially capable young applicant from India. “Dear Sir/Madam!” had this person really visited my website and failed to unambigu- Aseem's web photograph ously tell my gender from my mugshot? Even if this were true, coming from India, they should have guessed my gender from my fi rst name. My annoyance faded as I recalled a request that I had sent 20 years earlier to a preeminent sci- entist, Professor Obaid Siddiqi, at one of the best research institutes in India. I had laid bare my soul and waxed on about how this experi- ence would truly permit me to decide whether I should pursue a career in science or, like my mother, become a member of the Indian Navy. I expected an immediate and equally long response Har Gobind Khorana by return mail. And so when just a 10-word reply arrived, I was crushed– even though the message were missing the boat by not establishing a simi- was “I welcome you to join my laboratory for the lar program with India. He smiled and walked me summer.” over to Ken Shapiro (Associate Dean of CALS) Th e experience changed the trajectory of and Kim Santiago (Asia outreach coordinator, my life. I realized that there was pressing need who had organized the A*star evening). “Ken,” for a high quality “match making” program that he said, “Aseem here is volunteering to build identifi ed qualifi ed students and placed them in an Indian A*star program.” I had done no such labs where they would be nurtured and given the thing, but Ken, a charming, mild-mannered, but opportunity to engage in solving exciting prob- very action-oriented Dean for International Pro- lems at the frontiers of science, medicine and grams was not about to let that get in his way. technology. He chatted with me quietly about Indian institu- tions, post 9/11 visa complications, UW policy Genesis and Ken Shapiro on foreign students, and his interest in connect- Th ese thoughts crystallized one evening at ing UW to as many countries as was possible. the Fall 2005 annual gathering for the A*star stu- Kim would interject whenever we digressed, dents from Singapore. Th e government of Singa- expressing enormous enthusiasm for engaging pore identifi es a handful of outstanding students India and linking the many UW alumni who – “A*star” students – who they then fund from hailed from that subcontinent. college all the way through their fi nal degree (for In January of 2006, at a conference in India Ken Shapiro and Kim Santiago example, a PhD). Th e stu- I heard Arabinda Mitra of the Indo-US science dents have the freedom to and technology forum, or the IUSSTF, extolling choose any institution and the virtues of joint research and exchange of scien- roughly any area of study. tists. “Tired maxims,” I thought, but Mitra jolted Th e students are excep- me out of my cynical state with the magic phrase: tional and an absolute joy to “Money is not a problem. We have money and mentor. are looking for interesting ideas to fund.” Th e At the end of the recep- IUSSTF was brimming with funds and had con- tion, I was standing around tributed to the joint Indo-US meeting that had awkwardly chatting with brought 40 high profi le US scientists to India. Chancellor John Wiley Mitra off ered to seriously consider anything when I pointed out that we consistent with the IUSSTF mission to foster 26 productive and long-term interactions between times to make sure I hadn’t misunderstood. Julius India and the US. Could we get support from the Adler caught me in the act and explained that, in IUSSTF to develop a UW program with India? fact, Gobind had been a faculty member in our Th e answer may take the form of travel awards for department (and the Enzyme Institute) for nearly students and scholars from both nations. a decade. “He did it all here, in that building.” Why then is there no endowed chair in his name Nucleation: Khorana and Adler in the department? Julius shrugged and then in Ken Shapiro was unrelenting in his mission his wonderful way went on to recount some of the to ensure that the program memorable times he had with Gobind. “But you took form. We had several know, he is unwell these days.” It took less than meetings over 2006. Ken a second to suggest that we name the coalescing would pull out his little student program the “Khorana Scholars.” Julius leather bound black book followed through with an email to Gobind to and take copious notes and let him know about this nascent plan. A few then, abruptly, nearly a year days later he informed me that Gobind seemed after the A*star gathering, pleased by the suggestion. Th e “Khorana Scholars he put down his pencil and Program” was born. in a soft but fi rm way he said, “enough talk, let's just Th e pilot project do it.” I asked my colleagues to send me the “Dear But do what exactly, Sir/Madam” letters that they found interesting but and how? Shaped by inces- inscrutable in terms of scholastic aptitude, quality sant grant writing, my of institutions, and such. I pruned a very long list Khorana marker instinct was that approach- to 50 very talented candidates, got transcripts and ing IUSSTF without “preliminary data” was pre- letters, and narrowed it to about 10 candidates; mature. Moreover, the college (CALS) had just phone interviews cut it to 5 fi nalists. In the end told us that they had no money for a non-essential we matched fi ve students with fi ve colleagues. program. “So start a pilot project that I will fund To my horror, one colleague erupted, “But this from the tin can under my pillow,” Ken coun- student was ranked a thousandth in the entrance tered. Walking back from that meeting I nearly exam!” I rushed to explain that nearly 400,000 ran head-on into a no-nonsense metal marker students prepare for nearly two years to take the that honored the work of Har Gobind Khorana grueling IIT-JEE (Indian Institutes of Technology at UW. Th e marker declared that Khorana won - Joint Entrance Exam) and only the top 1-2% get the Nobel prize at UW in 1968 for his work in into these elite institutions. Th e Infosys chairman deciphering the genetic code. He went on to famously quipped “IIT rejects” win top honors Gobind with Julius and make synthetic genes. No scientist from India is at Caltech and Harvard, so a rank of 1000+ from David Adler complete if they don’t know these factoids from the best IIT was actually quite respectable. In the moment when they are the end, Ken could fund only three students. To anointed as “science majors” help the program take its fi rst tentative steps, the in their late teens. Th ey may department chairperson Elizabeth Craig gener- not know what the genetic ously off ered a supplement of $1000 per student– code is or what a synthetic an amount that made an enormous diff erence in gene may be or how this the students’ ability to buy food. led to the birth of modern molecular and chemical biol- Th e pilot project was on! ogy, but by God, we know of Khorana’s greatness and that Transformation he did transcendental things Graduate students from the host labs at at MIT. UW made the visitors feel welcome. Jackie Read- So why was this ing warmly introduced them at the departmen- unyielding marker claiming tal retreat and Jeet Kalia, a former IIT gradu- that he had cracked the code ate, took them under his wing. We took pains at UW? I re-read it a couple of to place them in nurturing and exciting labs at 27 encountered during their trip. Ken Shapiro too had gone to Uganda with James and was tremen- dously moved by the work. Greatly impressed, I wondered if the Khorana program should also seek to incorporate a similar “exchange” compo- nent to take UW students to India? Th e program thereafter was rebaptized the “Khorana Exchange Program.”

A whirlwind through India At the end of summer 2007, with the pio- neering Khorana fellows back in India and my tenure process in full swing, Ken gracefully stopped asking me to more meetings. As soon as a positive departmental vote on my tenure came through, Ken suddenly reemerged from the shadows with the request that we visit India. Our goals were ambitious– we wanted to iden- tify partner institutions in India, gauge the inter- est of these institutions in a scientifi c exchange program, learn about areas of relevance to Indian Mukul, Ishan and Arpita, the fi rst group of Korana Scholars scientists, engage the Indian government and lay the ground work to formally launch the program UW. Arpita Mandan worked on RNA-protein in the fall of 2008– all this in time for the 40th molecular recognition (in Marv Wickens’ lab), anniversary of Khorana’s Nobel Prize award. Ishan Chaturvedi spanned a couple of labs At this stage we reconnected with Kim San- working on nanofabrication with Franco Cer- tiago, who arrived with a list of alumni going rina in engineering and Robert Blick in phys- back to when India was still part of the British ics, and Mukul Garg worked on bioinformatics Raj, and Mahatma Gandhi had not yet returned and microbial genomics (in Bob Landick’s lab). from South Africa to spur on the Indian freedom At the end of their 10 weeks they were fi ghting movement. In looking at the alumni list, Sankar tooth and nail with the IIT administrators to stay Adhya’s name jumped out at me. A prominent on another week and another day and another molecular geneticist at the National Cancer Insti- hour… Finally, they could stay no more and they tute in Bethesda and member of the prestigious gave their presentations to the department. Th e National Academy of Sciences, I had known subsequent windup meeting with Dean Shapiro him from the start of my graduate career. I asked was especially touching. him for advice and he suggested we contact Dr. Mashelkar, (a visionary former head of the Coun- Exchange cil for Scientifi c and Industrial Research (CSIR) An amazing and quite diff erent program and Dr. Balaram, another leading scientist and soon came to my attention. James Ntambi, has the director of the Indian Institute of Science created a remarkable program takes a group of (IISc) in Bangalore. Th e latter institution seemed students to Uganda and intimately introduces like a natural home for UW students, because of them to various health and nutritional issues its scientifi c excellence, academic breadth, set- facing the populace (see page 5 in this newslet- ting in the former royal botanical gardens in the ter, for his update). Students take a class in the lovely city of Bangalore, and the sheer volume of fall semester and then over the winter break, the UW alumni on its faculty. under James’ tutelage, attend workshops and Working non-stop for two and half months, work in camps in Uganda. Many students fi nd it Ken, Kim and I lined up 50 meetings that we a transformative experience: some have gone on would have in 7 cities across India over a span to start their own non-governmental organiza- of 14 days! We met with Directors/Chancellors, tions to continue work on the projects that they Deans, Department chairs, and students from

28 over 12 academic institutions - and even explored lor Wiley, both known for fi scal prudence, off ered experimental farms. We met with the former to bankroll the program - completely unsolicited. Prime Minister (Mr. I. K. Gujral), the current cabinet Minister of Science and Technology (Mr. A new and ambitious identity Kapil Sibal), and heads of the major scientifi c From our discussions with friends and poten- organizations (CSIR and the Dept. of Biotech- tial partners, three major objectives emerged: nology). As we crisscrossed India, ministers, gov- ernors, academicians, industrial giants, alumni 1. Provide Indian and American students with - nearly everyone - added new dimensions to our a transformative experience objectives. Th e breadth of excellence across UW allowed us to fl esh them all out. In Bangalore, 2. Engage in Indian rural development we met with Obaid Siddiqi, who nearly 20 years earlier had started me on my academic path. 3. Increase interaction between academia and None of this would have been possible the private sector between the two nations without the help of alumni and friends such as Krishna Ella of Bharat Biotech, who went out Th e third objective illustrates how the objec- of his way (literally, he came to Delhi and Banga- tives of the program were shaped by suggestions lore from his company head quarters in Hydera- of the people we met. In a meeting arranged bad) to arrange and shepherd the meetings with by Raj Rajaram we presented our objectives to the government. Dipankar Chatterji, at IISc, Sam Pitroda, who then strongly encouraged us allowed us to introduce the Khorana program to aggressively engage in rural development. Th e to biomedical scientists from all over India and Indian consul-general in Chicago (Mr. Ashok the Pacifi c Rim at the Asian Conference of Tran- Attri) seconded that notion and another dimen- scription (ACT-X at Bangalore). And through sion to our program was added – rural develop- the courtesy of Raj Rajaram, a member of the ment in all its avatars is now a major objective of UW alumni board, and Sam Pitroda, the chair- the Khorana Program. Soon after our fi rst visit man of the Indian National Knowledge Com- we were immediately invited back to India by mission, the program was given a prime time Mr. Rahul Gandhi and the Rajiv Gandhi foun- showing by Srinivasa Rao at the annual meeting dation to fl esh out this objective. of the Indian National Science Academy (INSA) Th e Khorana program, we anticipate, will with its 5000 attendees. S. Viswanathan, who provide a life-enriching experience for students visited UW and was the fi rst to suggest that we from both nations, build bridges between work with his foundation on agricultural pro- scientists/institutions and lead to virtual and ductivity, invited us to present the program to seamless scientifi c communities across the world. the Governor and the former Governor of Tamil If it continues along its current trajectory, and if it Nadu and a slew of infl uential agricultural tech- garners further support from friends and alumni, nocrats. Masood Akhtar, a Madison-based the program will grow beyond undergraduates, entrepreneur who was once with Forest Products beyond summer exchanges, beyond chemical lab, set up meetings with the Vice Chancellor of biology, beyond the current boundaries and his alma mater and in an inspired moment he would make UW the focus of a much broader even off ered to fund a Khorana fellow from Ali- program between US and India. Th e scope may garh to Madison. Finally, in Delhi, we benefi ted match that of the Fulbright program but with an from the charm and hospitality of Ravi Khanna emphasis on Science, Medicine and Technology. who helped fi re up an informal alumni meeting. Th e challenge now will be to make the Khorana Trained as an electrical engineer at UW, this real program self-sustaining and retain its nimbleness estate magnate also expanded our horizons with to adapt to new and unanticipated areas of discussions of metaphysics and nature of con- interest and most importantly, to maintain its sciousness – between libations that foster fl uidity excellence. of mind. More information on the program can be Finally, as tangible evidence of the wide- found at the following website: spread enthusiasm for the program, the Indian https://www.biochem.wisc.edu/faculty/ government’s Minister Sibal and UW’s Chancel- ansari/khorana_program/

29 Biochemistry Degree Listing May 2007-December 2007 Degree Name (Major Professor) Thesis Title

PhD Kanin, Elenita Chemical Genomics Analysis of TFIIH Kinase Function in (Ansari) Saccharomyces cerevisiae

PhD Raess, Phillip A novel role for cholecystokinin in beta-cell growth and survival (Attie)

PhD Davis, Jared H. Structure, thermodynamics and metal ion association of the GAAA tetraloop- (Butcher) receptor interaction in solution

PhD Cox, Julia M. The Coordinated ATP Hydrolysis Activity of the Escherichia coli RecA Protein (Cox)

PhD Harris, Dennis R. Investigating the Phenomenon of Radioresistance in Bacteria using Deinococcus (Cox) radiodurans and Hyper-evolved Escherichia coli

PhD Rudolph, Ehren N. Characterization of the protective effect of 1α, 25-dihydroxymitamin D3 in the (DeLuca) nonobese diabetic mouse

PhD Borrock III, Martin J. Ligand Recognition and Signal Transduction in Bacterial Chemotaxis (Kiessling)

PhD Puffer, Erik B. Exploring B Cell Receptor Function Using Defined Multivalent Ligands (Kiessling)

PhD Chesney, Michael Molecular and genetic analyses of GON-14 and other transcriptional regulators (Kimble) of early gonadogenesis in C. elegans

PhD Suh, Nayoung Molecular controls of mitosis/meiosis decision in C. elegans by conserved RNA (Kimble) regulators, FBF and GLD-2

PhD Lynch, Kara L. Determination of the functional relevance of synoptotagmin and its Ca2+ (Martin) dependent interactions in exocytosis

PhD Lim, Pei-Yin The glycosaminoglycan-independent entry pathway utilized by herpes (Montgomery) simplex virus

PhD Groppo, Rachel P. Characterization of cellular translation components during cardiovirus infection (Palmenberg)

30 Degree Name (Major Professor) Thesis Title

PhD Fretz, Jackie A. Exploring the Transcriptional Activities of NFATc1: The Master Regulators of (Pike) RANKL-Induced Osteoclast Formation

PhD Meyer, Mark B. Molecular Mechanism Controlling TRPV6 Gene Expression and Calcium (Pike) Homeostasis by Vitamin D Ligand

PhD Johnson, Randal Jeremy Ribonucleases: Structural and biochemical insights into cytotoxic activity (Raines)

PhD Davis, Caroline A. The Role of Upstream DNA Wrapping in Transcription Initiation by Escherichia (Record) coli RNA Polymerase

PhD Vander Meulen, Kirk A. Characterization and Analysis of the DNA Binding Thermodynamics of (Record) Integration Host Factor

PhD Gradman, Richard J. Analysis of control mechanisms in Tn5 transposase (Reznikoff)

PhD Krusemark, Casey J. Synthetic Chemical Approaches to Proteomics: Affinity Labeling and Protein (Sussman) Functional Group Modification

PhD Kwak, Jae Eun GLD2 proteins: polyadenylation, polyuridylation and memory formation (Wickens)

PhD Liu, Lingling Centrosomal proteins required for microtubule organization (Wiese)

MS Thomson, Brian J. 2-Methylene-19-nor-1α-hydroxyvitamin D3 analogs inhibit adipocyte (Clagett-Dame) differentiation and PPARγ2 gene transcription

MS Davis, Melissa L. Structural and functional analysis of selected enzymes involved in the biosynthesis (Holden) of the S-layer glycan of Aneurinibacillus thermoaerophilus L420-91T

MS Weir, April M. A Chemical Biology Approach Towards the Elucidation of Human Embryonic (Kiessling) Stem Cell Signaling

31 Department of Biochemistry Alumnus – Jason Gestwicki by Professor Doug Weibel Th e Wisconsin Years clustering in bacteria, Jason identifi ed how Jason Gestwicki grew up in New York inter-receptor interactions play a role in State and studied chemistry at SUNY Fre- amplifying and integrating chemotactic donia. Several faculty members at Fredo- signals in Escherichia coli. Th is work built nia remember Jason fondly and recount upon the pioneering work of Professor his fl air for fashion with a sense of nostal- Julius Adler on chemotaxis in E. coli and gia. Fredonia alumni remember Jason for the distinguished history in this depart- his unusual humor and his unique comic ment of decoding signal transduction in strips. In 1997 he moved to the University bacteria. Jason was remarkably productive of Wisconsin-Madison as a graduate stu- at UW-Madison and published 17 papers dent in the Department of Biochemistry and review articles. His love of science was Jason 2001, Madison and fell in love with chemical biology. obvious to those around him and he was Jason’s fi rst encounter with the emerg- a central character in a variety of events ing fi eld arose during his fi rst conversation focused around discussing science and phi- with Professor Laura Kiessling. Laura gave losophy late at night in the lab, at the Ter- Jason a reprint of a paper from Professors race, and at the Regent Street Retreat. Gerald Crabtree and Stuart Schreiber that described the application of small mole- Chemical Biology Gold Rush – Go cules to regulate protein dimerization. Th at West! paper introduced Jason to the concept of After graduating in 2002, Jason joined using synthetic ligands to dissect biologi- Gerald Crabtree’s group (remember that cal systems and inspired him to pursue a infl uential paper mentioned earlier?) at path in chemical biology that he continues Stanford as a postdoctoral fellow. At Stan- to tread along. ford Jason explored a new strategy for Following his rotation, Jason joined inhibiting protein/protein interactions. In the Kiessling laboratory and used syn- 2004 they published an important paper thetic, multivalent ligands to study the that outlined a strategy for using small mol- regulation of receptor signaling in bacterial ecules to inhibit the aggregation of amyloid chemotaxis. Jason’s graduate dissertation β in vitro (Science, 2004, 306, 865). advanced our understanding of how bacte- rial cells rectify incoming signals and pro- From Badger to Wolverine duce a coherent behavioral response. Using In 2005, Jason moved back into the Jason with his lab group, chemical probes to study chemoreceptor Big Ten and became an Assistant Professor 2006 Ann Arbor in the Life Sciences Institute at the Uni- versity of Michigan. Th e Gestwicki group uses small molecules to study the roles of molecular chaperones in disease. Using an approach based largely on chemical biol- ogy, they are exploring how chaperones rec- ognize and process misfolded polypeptides, and how these interactions determine the outcome of neurological disorders, includ- ing Alzheimer’s and Huntington’s disease. He’s back in the Big Ten where he started. Th is time, however, he is the one handing out classic papers in chemical biology to eager fi rst year students and extolling the virtues of using small molecules to under- stand biological systems. Th e educational circle of life, which began at UW-Madison, continues today.

32 From the Labs Th e Attie lab is delving ever more deeply into Jaap and Arlene live in Hillegom in the Nether- genetics of diabetes. Our lab has completed a large lands, between the tulips, where they spend most study where we are identifying gene loci that con- of their free time rebuilding and refurbishing their trol gene expression of many thousands of genes (old) house. Th ey have 2 cats for company. Free in various tissues in relation to obesity and dia- time is otherwise spent on softball, dancing, play- betes. Th e volume of data before us has made us ing the trumpet (very early stages), and of course develop a web site that allows us to probe our large enjoying those beautiful fl owers! data sets. We have made part of our data publicly Dan Gretch is now an Associate Professor at Alan Attie available: http://diabetes.wisc.edu. Carroll College in Helena, MT. He is teaching Lab Below are some news items from various past Biochemistry and Genetics, as well as conducting and present members of the Attie lab. research on prion protein misfolding in Chronic Angie Oler is a biochemist turned geneticist. Wasting Disease. Living in Helena places him She is currently chasing diabetic genes on mouse within 20 miles of 4 lakes, dozens of hiking trails, chromosomes 16 and 2. Most of her days, she is 20+ campgrounds, and the continental divide. If up to her ears in pancreatic islets. She spends her you are visiting MT, stop by and say hello! free time playing volleyball on her home court Scott and Amy Cooper are enjoying a very and traveling the ever expansive globe. white Wisconsin winter. Scott's new challenge Summer Raines is continuing her graduate in his 13th year of teaching at UW-LaCrosse is a work in the Attie Lab, with a focus on vascular- course in radiation biology. He's already hit Scott ization of the pancreatic islet. Outside of lab, Lowe up for some suggestions on using p53 in the she recently became engaged to Greg Jakubczak lab section. (former Raines lab manager), and is planning a Paul Bates is teaching Freshman and wedding for September 2009, (hopefully) follow- Advanced Placement Biology at Edgewood High ing her graduation. School. He is also an Adjunct Professor at Edge- Phil Raess is enjoying his third year of medi- wood College, teaching Biotechnology as well as cal school, doing clinical rotations at the UW supervising some undergraduate students in their hospital and in outlying communities. He and research projects. Th ey are studying hybridization his wife Nicole have been enjoying cross-country between native and invasive species of the aquatic skiing this winter in their rare free time. Phil will plant milfoil at the anatomic and DNA levels. In graduate from the MSTP in 2009, and has yet to his free time, he's building furniture for his home decide on his medical specialty. and training for his second marathon. Susie Clee left her position in the Depart- After completing her doctorate degree in ment of Biochemistry at the end of June last year. 2006, Jessica Flowers went on to become a reg- She is currently establishing her own lab as an istered dietitian after completing an internship in Assistant Professor in the Department of Cellu- dietetics at the University of Wisconsin Hospital lar and Physiological Sciences at the University and Clinics. She is currently participating in the of British Columbia in Vancouver. Her work will Waisman Center Leadership Experience in Neu- continue to focus on using genetics as a tool to rological Development interdisciplinary training identify novel pathways increasing susceptibility program and she recently started working as a to developing obesity and type 2 diabetes. nutritionist for the research diet design company Jaap Twisk has been working at Amsterdam Harlan-Teklad. Molecular Th erapeutics (Amsterdam, The Neth- Don Gillian-Daniel is now an Associate erlands) since 2002, where he is involved in a Director of the Delta Program in Research, Teach- number of gene therapy projects. Th e most prom- ing and Learning at UW (www.delta.wisc.edu). ising project involves adenovirus-associated virus He recently co-authored a book chapter about (AAV)-mediated expression of Lipoprotein Lipase the program, "Preparing Future STEM Faculty," (LPL) in muscle, as a treatment for Type I LPL to appear in the Monograph Series: "New Direc- defi ciency in man. Th e project has evolved from tions in Teaching and Learning." Don also teaches designing the vector, testing it in LPL-defi cient metabolism in the Vet School each spring (Alan's mice and cats, to clinical testing in patients. Jaap old course), where he gets to try out all kinds is mostly involved in research management but of new pedagogy on the unsuspecting students! spends part of his time at the bench as well. Anne Lynn is the Program Administrator for the

33 NMRFAM with John Markley. I have been on the "dark side", pharmaceu- Dawn Brasaemle, Associate Professor in tical industry as my academic friends call it, for Nutritional Sciences, Rutgers University, orga- three years. I chase new drug targets in obesity nized the fi rst ever conference dedicated to and diabetes. An industry job relies heavily on the biology of lipid droplets as a 2007 FASEB team work and collaborations. I don't need to Summer Research Conference. Th e conference run all the experiments, but I need to work with was a huge success, and was attended by Attie my colleagues or with outside service companies lab alum Steve Sturley, who gave a brilliant talk to get results as fast as possible. I spend a large (as usual). Th e conference will continue as a amount of time writing e-mails and attending regular meeting with the next one scheduled for various meetings, coordinating group eff orts. I Summer 2010. enjoy working with my colleagues. Th omas Baranski was promoted to Associ- Kurt Grunwald is taking his last class towards ate Professor at Washington University where he his degree(s) in Physics with Astronomy Empha- continues his research on signal transduction by sis and Math. He has accepted a new position at G proteins. He has also initiated a new project UW-La Crosse as the equipment maintenance in the lab that focuses on glucose toxicity and manager. He will be responsible for maintenance insulin resistance in a Drosophila model system. and repair of the Biotech equipment in Biology. As an added benefi t, this project has precipitated He is also the Radiation Safety Offi cer at UW-L. discussions and video chats with his former His oldest son is in middle school, his daughter mentor, Alan. Capitalizing on this technology, is in elementary school and his younger son will Tom co-founded a company, Medros (Medi- start kindergarten this fall. Kurt and his son Alex cines from Drosophila) that uses whole animal are active Boy Scouts. Kurt is slated to become screening to identify novel drugs for cancer and the Scoutmaster for their troop next year. With diabetes. Tom remains happily married to Karen any free time Kurt is a part time business partner and his family continues to grow. He has three in a woodworking business making yoga props children--Katie (9), Elizabeth (6), and Jack (4). at "Yoga Place Props."

Another year has fl own by, and it has been an year graduate students Steve Martin-Tumasz and exciting and productive one in the Butcher lab. Ashley Richie are continuing our work on pre- Below are a few highlights. mRNA splicing, focusing on the structure and function of the U6 small nuclear ribonucleopro- Science: tein particle. Rita Warden helps to keep things We determined our fi rst protein structure! We running on the fi rst fl oor and divides her time (meaning mostly Nick Reiter) solved the NMR administratively helping out all 3 fi rst fl oor labs structure of Prp24, an essential splicing factor and (Markley, Butcher and Fox). Sam Butcher U6 RNA binding protein. Collaboratively with Lab George Phillips and Dave Brow, we also solved New Arrivals: its crystal structure. Th ankfully the two structures We are really happy that two wonderful new agreed nicely. Over the past year, we’ve also solved graduate students joined the lab: Jordan Halsig a few (actually around 5) new NMR structures, and Katie Mouzakis. Jordan will be investigat- all very interesting RNAs that include: a U2 spli- ing the structure of the spliceosomal U2-U6 ceosomal RNA domain (Dipa Sashital), a retrovi- RNA complex, and Katie is working on the ral frameshift site RNA from SIV (Ryan Marche- HIV-1 frameshift site RNA and trying to target schi), an HIV-1 frameshift site RNA bound by a it with small molecule antagonists. Additionally, drug-like small molecule (David Staple), an anti- two new postdocs have recently joined the lab: NF-kappaB aptamer (Nick Reiter), and a tetra- Kirk Vander Meulen, (from the Record lab), loop receptor domain from a self-splicing intron and Larry Clos. Kirk is studying the thermody- complete with bound metal ions (Jared Davis namic forces that drive RNA folding, and Larry and Trent Foster). Additionally, we developed a is working on the structure of U6 RNA. Two new new method for probing the surface accessibility undergraduates also joined the lab (Hyunjae Lee of nucleic acids, using NMR and a highly soluble and Chen Yuan Kam). paramagnetic probe (Vincenzo Venditti). Second

34 Departures: Dipa Sashital left for her postdoctoral position Nick Reiter left after 6 productive years and (with a Damon-Runyon Postdoctoral Fellowship 5 fi rst author publications, setting a great exam- Award in hand!) in Jennifer Doudna’s laboratory ple for future graduate students. Nick is now at Berkeley. Finally, our fabulous undergraduate a postdoc with Prof. Alfonso Mondragon, an and RNA biochemist extraordinaire Trent Foster outstanding crystallographer at Northwestern. left for medical school here at UW-Madison.

Our group has increased in size by 2 this year. mechanism for intermediate transfer between Tonya Zeczycki is a new postdoc in our lab. She active sites and a structural basis for allosteric received her Ph. D. in organometallic chemistry activation. from Marquette University. She moved here in Mark Anderson completed an isotope study August with her husband Jay. Besides spending a showing the symbiotic relationship between zillion hours in lab, she likes to paint with water- leaf-cutter ants and nitrogen fi xing bacteria. Th e colors. She is working on determining isotope work was done in collaboration with Adrian eff ects on pyruvate carboxylase and its mutants. Pinto from the Currie lab in the Department of Mo Cleland Nate Bruender is new graduate student. He is Bacteriology. Th e manuscript will be submitted Lab originally from near Mankato, Minn and received to Nature in February. He is also collaborating his degree in biochemistry from the University of on the kinetic isotope eff ect (KIE) studies of Minnesota-Duluth. He is a big hockey fan and the reactions catalyzed by nicotinamidase and plays intramural hockey in Madison. He is doing Sir2 with Brian Smith from the Denu lab at the a joint project including both kinetics and x-ray Department of Biomolecular Chemistry. Other crystallography with the Holden lab. projects include collaboration with Russ Poyner Professor John Marlier fi nished his project of the Reed lab to determine kinetic isotope on determining the isotope eff ects of slow sub- eff ects for ethanolamine ammonia lyase using strates with urease, and Professor Jill Rawling's various 15N, 13C, and 2H labeled substrates. work on the reduction of hydroxyamine was uti- Mo and Laurie went to the Enzyme Mecha- lized by both John and Jeremy Van Vleet, in his nism Conference in St. Petersberg, Florida, in last year of graduate school. Jeremy and Laurie January. It was gorgeous there. Mo went to the Reinhardt, associate scientist, published a paper Enzymes Gordon Conference in Maine, and is in Biochemistry supporting the formation of a looking forward to the Isotopes Gordon Confer- discrete carbanion intermediate in the decar- ence in Ventura, CA, this February. boxylation reaction of orotidine-monophosphate We have fi ve undergraduates working with decarboxylase, perhaps putting an end to that us. Fiona Chu runs the high vac lines and mass controversial story. Martin St. Maurice, a post- spectrometer like a pro. Greg Peters, our kinetics doc in the Rayment Lab, and Laurie published and columns undergrad, is graduating this year. a report in Science on the X-ray structure of Dan Pensinger and Min-Hee Han are working pyruvate carboxylase, a multifunctional enzyme. with Jeremy. Ryan Gries is starting to work with Th e structure reveals a previously unrecognized Tonya. Elisa Parks graduated in December.

Current Lab News: Awards: Vessela Petrova passed her prelim exam in Audrey Klingele received a 2007-2008 Vilas April 2007. Congratulations Vessela! Travel Award to use to attend the Keystone Sym- Mike Cox and Dave Nelson completed the posium on DNA Replication and Recombination Principles of Biochemistry, Fifth Edition, as well as in Santa Fe, New Mexico, in February 2008. She’ll Mike and George Phillips completing the Hand- attend the meeting with Mike Cox, Jong-Il Kim book of Proteins: Structure, Function and Methods. and Marielle Gruenig. Two books in one year, along with chairing the Mike Cox New Building committee, teaching, speaking, and Comings: Lab all the other things a PI does. How does he fi nd the Graduate students Asher Page and Khanh time to do it all? Ngo joined the lab after fall rotations.

35 Cédric Norais joined the lab as a postdoc in Fremont, California. She said she’s on the Corpo- November 2007. He was previously a graduate rate and Business Development team. student in the lab of Dr. Hannu Myllykallio at the Brian Webb now works for Th ermo in Roscoe, University Paris-Sud. He received his PhD in July Illinois. He leads a group of scientists developing 2007. He is joined in Madison by his wife, Vir- antibody arrays and siRNA products. ginie and his son, Alban. Welcome to the Cox Lab Cédric, Khanh and Former Cox Lab undergrad news: Asher. Mike Modica wrote a note in early 2007 saying he fi nished up medical school and was in Goings: the process of interviewing for medical residency. Dmitry Baytin left the Cox Lab to return He said he’s interested in molecular imaging as a to St. Petersburg, Russia and the lab of Vladislav research focus during residency. Reece Goiff on Lanzov in July 2007. joined the MD/PhD program at Washington Uni- Julia Cox defended her thesis February 2007 versity in St. Louis. and is working as a patent scientist at Michael Best & Friedrich, LLC. Congratulations Julia – we miss Babies and Weddings: you. As mentioned above Dennis Harris and Dennis Harris defended his thesis in May Yeajin Song were married in May 2007. Th ey had 2007 and is currently a postdoc in the Miro another ceremony in Maryland on a beautiful day Radman Lab, Institut National de la Santé et de la in August to include all family and friends. Imme- Recherche Médicale (INSERM). On the evening diately following the ceremony they were off to of the day that Dennis defended his thesis, he and Paris. Yeajin Song were married - a day full of excite- Kevin Rice, Anna, and TJ gave us news that ment and instant memories. Congratulations to they are now a family of four. Jenna was born on both Dennis and Yeajin! Dennis sent us an email March 21, 2007 and weighed 7 pounds 15 ounces. in September 2007 soon after they arrived in Paris, Welcome to the Cox Lab family Jenna. Kevin sent saying that they have a full view of the Eiff el Tower us a note in July saying that along with all his other right outside their apartment window and that news, he and Anna just purchased their fi rst house they get a light show every night before they go to too. What a year for the Rice family! sleep. Nice! Julie Schultz (Bork) wrote that she and Todd are now the proud parents of Jessica Lena Schultz, Past Lab News: born October 11, 2007 and weighed 6 pounds 7 Kevin Rice is now an Assistant Professor at ounces. Julie says Jessica has lovely red hair and Colby College in Waterville, Maine. His website that their lives will never be the same. Congratu- is: www.colby.edu/chemistry/Rice/Welcome.html. lations to Julie, Todd, and Jessica - all the best to Sarita Jain is now at PDL BioPharma, Inc in you.

36 Hello from 141B Biochemistry Addition and colleagues. Latest score from PubMed: Post-Fox, 4th fl oor of Old Genetics. Rogge:6; Fox-Rogge:3; Pre-Fox, Rogge:0. Way It has been a couple of years since I wrote, so to go Cory! there is some catching up to do. Our projects are Luke Moe and Michelle Sizemore got still the desaturases and toluene monooxygenase married last summer just before July 4th at the along with cloning, expression, growth, and puri- Olbrich Gardens. Even yours truly was photo- fi cation subgroups in the UW Center for Eukary- graphed on the dance fl oor. It was a good time, otic Structural Genomics (CESG). Most recently, and I had a nice, by-chance visit with Luke’s par- Brian Fox our group has also begun work in the biofuels ents at the Ground Zero coff ee shop the next Lab area, using our expression approaches to prepare morning. Luke is now a postdoctoral fellow in enzymes useful for cellulose degradation. Jo Handlesman’s lab. Luke has the unique career Over the past couple of years, the lab per- path of moving to a new lab in every position he sonnel has included Abolfazl Arabshahi, Lucas has accepted so far. He has our best wishes that Bailey, Lai Bergeman, Paul Blommel, Bren- he might continue on this lucky course. dan Burns, Yong Chang, Nate Elsen, Ronnie Tom Malone fi nished his PhD dissertation Frederick, Mike Goren, Carrie Loushin-New- in December 2006, and Paul Blommel fi nished man, Th omas Malone, Lea McMartin, Luke his PhD dissertation in May 2007. Tom identi- Moe, Karl Nichols, Brad Pierce, John Primm, fi ed a new XenB enzyme by Cartesian analysis Megan Riters, Kory Seder, Pablo Sobrado, of product specifi city, and recently my friends at Dmitriy Vinarov, Frank Vojtik and Russell Shaw Environmental (formerly Envirogen) have Wrobel. Rita Warden helps to keep me orga- gotten interested in this enzyme. Paul is work- nized, which is no small feat. Undergraduates ing at a startup company on converting sugar working in the lab have included Petar Duvnak, to gasoline, so there is at least some glimmer of Andy Hauser, Steve Kaul, Jacob Ludington, Yi hope that Hummer drivers (and Professors with Han Ng, Kaitlin Statz, Justin Tannem, Nicho- mini-vans) will be able to continue their profl i- las Turco and Abby Wochinski. We have also gate way. had Carissa Amundson and Cody Sizemore After a minor scare on renewing her visa last from the Dane County Youth Apprenticeship summer (biophysics and Mycobacteria, possibly program. Of note, Petar is now in medical school scary), Yong Chang made it back to Madison at Medical College of Wisconsin, Steve works at and has completed work for at least two papers Sigma/Aldrich, Andy is our lab manager, and Yi on Mycobacterium tuberculosis desaturase pro- Han has a Hilldale Fellowship to complete her teins. Recent news is that Yong Chang will be dissertation research. married this year. She is currently in China plan- Brian Hoff man and Jeremie Pikus, please ning the wedding. Our congratulations. contact me sometime. Pablo Sobrado is now an Assistant Professor Joe Studts and John Broadwater both work in the Department of Chemistry and Biochem- at Boehringer Ingelheim. I have had the good istry at Virginia Tech University. He is setting fortune of working with them and their cowork- up his program and has identifi ed some interest- ers over the past few years and hope that this ing topics on enzymology of pathogen enzymes activity will continue. Kevin and Tracey are and multiprotein complexes. Th is is an exciting now living and working in the Boston area at time as he begins to build his new research lab. biotech companies. Enrique returned to Mexico Last year, I gave a presentation at the Chicago to continue his research career after a strong con- ACS meeting at the Bader Symposium in honor tribution and an important learning experience of Prof. Eckard Münck. I talked on the protein- in the UW Medical School. Jeff and family are protein interaction model for desaturase, ferre- in Davis, CA, still the most ideal place in the doxin, and acyl-ACP that emerged from the Universe. Jeff made a summer visit to Madison a work of Pablo and Karen. year back, and it was nice to hear how well things Brad Pierce has accepted a position as are going for him and his family. Karen and Assistant Professor of Chemistry at University of Brandon have returned from Europe and now Texas Arlington. Brad has worked on many dif- live in the San Francisco area, fi nding the climate ferent metalloproteins in the past years includ- and temperament to their liking. No desiccation ing desaturase, toluene monooxygenase, cysteine there. Cory Rogge is still in the Houston area, dioxygenase, and FNR with Trica Kiley’s lab. He and publishing frequently with distinguished is one of the EPR experts on campus. Brad has

37 also been a leader in the Metals in Biology super- Japan and work with Prof. Yaeta Endo on this group, which meets once a month. topic. I had the pleasure of traveling twice to Lucas Bailey and Nate Elsen are work- Matsuyama, Japan to meet with Prof. Endo in ing on toluene monooxygenase. Some exciting the past year. results have emerged recently, including a 2008 My part of the CESG project has now moved New Year’s morning transmission of pdb coordi- to the fourth fl oor of the Old Genetics building. nates. After many years of eff ort by many diff er- Th is is a great space where everybody involved ent workers, Lucas Bailey succeeded in preparing in the Protein Production team is together. Th e the enzyme in a form that readily crystallizes. current team is John Primm, Frank Vojtik and With these crystals, Lucas has solved many dif- Donna Troestler (project management), Russell ferent structures of the hydroxylase at resolution Wrobel and Kory Seder (cloning), Ronnie Fred- lower than 2 Å. We owe a great deal of thanks erick, Lai Bergeman and Kasha Gromek (expres- to Jason McCoy, Craig Bingman, and George sion and large-scale production), Karl Nichols Phillips for help along the road to solving the and Mike Poplears (purifi cation), Shin-Ichi T4moH structures. Th ese structures comple- Makino (cell-free translation) and Dave Aceti ment the X-ray structures of T4moC solved by (quality control). Brendan, Megan, Dmitriy and Craig Bingman, Luke Moe and Gary Wesenberg, Carrie left the project to move on to bigger and and T4moD solved by George Lountos and Allen better things in the past year or so. Since the start Orville. We see new information on several early of Protein Structure Initiative Phase II in 2005, steps in the reaction cycle, and the crystal forms over 50 undergraduates and 7 high school stu- we have obtained show great promise to yield dents have worked with this group. I thank all of further information. In parallel, Nate has made them for their hard eff orts as they learn new skills major advances in our understanding of protein- that so strongly contribute to the project prog- protein interactions by use of stopped-fl ow and ress while also helping them advance their own rapid freeze quench approaches. Th e linkage of careers. CESG increasingly focuses on human the kinetics work and the crystal structures to proteins, and the thought that we can consider our large body of prior results will be an exciting the function of some of these is a satisfying new future eff ort. Th e fi rst presentation of this work direction. We wish them the best in their future will be at the New Orleans ACS meeting at the eff orts. Th e expression vector tools and methods Bader Symposium in honor of Prof. Larry Que. we have developed are very useful for production Mike Goren is the newest member of our of proteins, and if this is still in your work pro- group, coming from Glaxo Smith Kline by recom- gram, I encourage you to talk to us about these mendation of Jeff Gross, a former postdoctoral of methods. Perry Frey’s when we were located in the Enzyme In closing, I hope you and yours have been Institute. Mike is working on development of safe and happy over these past few years. It is my cell-free translation methods for membrane pro- wish that this will continue well into the future. teins. He recently won an NSF fellowship to visit Please stop by Madison if you have a chance.

The Frey Group made the transition to retirement of the Divisions of Organic Chemistry, Medici- for Perry during 2007. Th e symposium at the nal Chemistry, and Biochemical Technology and 234th National Meeting of the American Chemi- the Biotechnology Secretariat and Biotechnology cal Society in August went off very well, and more of Health and Wellness. Perry is very grateful to than a third of the former associates of the Frey these organizations for sponsoring the symposium Group were able to make their way to Boston for marking his retirement and for their past support the symposium and evening dinner. Th anks to of the activities in the Frey Group. John Richard, Joe Wedekind, Squire Booker, Several members of the group have secured Perry Frey Ken Gruys and Doug Sammons for their excel- new positions this year. Glen Hinckley is Assis- Lab lent presentations. Special thanks to Claire CaJa- tant Professor of Chemistry at Elmhurst College, cob for organizing the symposium and hosting the Sue Wang is Assistant Professor of Molecular Bio- dinner. Th anks also to the Division of Biological sciences at Washington State University, Dawei Chemistry of the ACS for proposing and sched- Chen is a research chemist at the Nanomaterials uling the symposium with the co-sponsorships & Nanofabrications Laboratories, Adrian Hege-

38 man is Assistant Professor of Horticulture and ating the group website http://perryfreygroup. Plant Biology at the University of Minnesota, biochem.wisc.edu/. Th e site includes informa- and Ab Arabshahi has transferred to the Great tion about the members of the group, with links Lakes Biofuels Center in the laboratory of Brian to their websites, as well as information about the Fox. Phil Schwartz is a postdoctoral associate at research activities of the group. We thank Ab for the Albert Einstein College of Medicine, and Ale- his good work in setting up the website. jandro Yevenes is a postdoctoral associate at Utah In retirement, Perry will continue working State University. Congratulations to all. with national organizations, editing and writing; Perry and members of the group are indebted he will pursue new personal challenges, and he to Ab Arabshahi and the Media Center for cre- will spend more time with his family.

Th e Kimble lab has continued to thrive in 2007 Knobel, a scientist from Maureen Barr’s lab who and early 2008. Indeed, for the fi rst time in joined us when Maureen moved to the east coast. living memory, every one has a bench of their Karla has a passion for cell biology and is focus- own — a situation we will try to maintain if ing her work on the distal tip cell and its role in at all possible. A real milestone for the lab has forming a stem cell niche. And another grownup been solving the SYS-1 crystal structure, a proj- is Clint Morgan, an M.D./Ph.D. student, who ect accomplished by posdoc Bryan Phillips in has joined the lab to do the research part of his our lab in collaboration with Wenqing Xu and dual degree. Th ese additions were made pos- Judith Kimble Jing Liu at the University of Washington in sible by the departures of others. Nayoung Suh Lab Seattle. It is tremendously exciting to move all defended her Ph. D. and departed for San Fran- the way from mutant to crystal structure, and cisco, where she will do her postdoc with Dr. fi nally demonstrate unambiguously that SYS-1 Robert Blelloch on the topic of microRNAs is indeed a bona fi de β-catenin. Another mile- in stem cells. Some of you may remember that stone has been the discovery of a conserved link Robert did his Ph. D. thesis with me – so need- found in the regulatory circuits controlling both less to say, I am excited about the idea that Nay- nematode and human stem cells. Postdoc Myon- oung will be with Robert for her postdoc. Mike Hee Lee found that PUF proteins downregulate Chesney defended his Ph. D. and departed for MAPK-encoding mRNAs in both C. elegans and Cambridge, England, where he will do his post- human embryonic stem cells, a project done in doc with Dr. Jim Smith on the topic of molecu- collaboration with Jamie Th omson and Marv lar mechanisms of vertebrate development. And Wickens here in Madison. Kate Schmitt, an undergraduate, who worked On the personal side, the lab has expanded with us for several years, has also left us, moving considerably over the past year, especially on on to fi nd her way in life. Well, this is obviously the baby front – our baby explosion makes our the short version of news from the Kimble lab, lab parties more fun than ever, albeit chaotic. so please stop by to say hello and get caught up One grownup who has joined lab is Dr. Karla if you are in the neighborhood!! – Judith

Th e greetings from the Lardy Lab are brief in We fi nally have secured a research grant but keeping with our small research group. Th e year it is so small that Dr. Padma Marwah is on a has been scientifi cally productive but the discov- 75% appointment and Dr. Ashok Marwah is eries have not yet been polished suffi ciently for receiving only 60% of his former salary. Both release. are so enthusiastic about their research that they We have lost some of our cherished col- have turned down lucrative, full-time appoint- leagues. You will read elsewhere that Prof. ments elsewhere to pursue our steroid work. Helmut Beinert died a few months ago. Among Nancy Kneer continues her work on an hourly Henry Lardy our former students, Dave Garbers died sud- basis. Lab denly this autumn, and Bob Weaver, Chair of We have leads that are highly interesting but Chemistry at U.W. Stevens Point, died after a they cannot be discussed until we decide on pat- prolonged illness. entability. More next year! – Henry

39 Comings and goings: ing an entire month in Wisconsin, John went to M. Francisca Jofre recently joined NMRFAM Osaka, Japan for a meeting on the role of isotope as a research specialist on the metabolomics proj- aided NMR methods for protein structural anal- ect and has added a signifi cant number of com- ysis. In April and May, John traveled to Colorado pounds to our ever growing standards database. and California to present a talk entitled “Lessons Two graduate students joined the Markley group from the Worldwide Structural Proteomics Pro- this year: Ziqi Dai is a biophysics student working grams.” After a trip to the UK in June for presen- with Hamid Eghbalnia and Arash Bahrami on tations on Structural Proteomics programs and John Markley developing the automated assignment software, Quantitative Metabolomics, John traveled to Lab and James Ellinger is a biochemistry graduate Paris in July to give a presentation on automated student, who will be working on a joint metabolo- protein structure determination at the Institut mics project with Ian Lewis and Mike Sussman. Pasteur. In October, John traveled to Taiwan for Klaas Hallenga will be retiring at the end of the 2nd Asia-Pacifi c NMR Symposium in Taipei March after fi ve years at NMRFAM. Klaas plans and the ISMAR Meeting in Kenting, which to move back to Th e Netherlands to be closer Milo Westler also attended. Honggao Yan, from to his children and grandchildren. We will miss Michigan State also attended the meeting. Th ey Klaas and his vast library of Varian knowledge. were hosted in Taiwan by former lab member Zsolt Zolnai, who continues to develop the Winston Wu. Ian Lewis gave a talk at the Red ‘Sesame’ laboratory information management Blood Cell meeting in Boston. Arash Bahrami system (LIMS) used by CESG, NMRFAM and presented a poster at the Keystone Conference in other groups, now works out of his apartment Steamboat Springs last January. in Brooklyn that overlooks the East River. Th e reason for the move is that Zsolt’s wife, Nevena, New Grants and Equipment: is doing her residency at several diff erent hospi- Fariba Assadi-Porter hit the jackpot this tals in the New York area. We miss having Zsolt year by becoming the PI of a Wisconsin Insti- on site, but he is in regular contact via phone, tutes for Discovery grant on the metabolomics e-mail, and video conferencing. Zsolt became the of polycystic ovarian syndrome (PCOS). Other PI of an NIH ‘R01’ grant last fall that is fund- lab members involved in the project are John, ing open source distribution of Sesame. Jurgen Hamid Eghbalnia, and Marco Tonelli. Fariba Doreleijers recently left BMRB to move closer also became a co-investigator on an NIH grant. to his family in Netherlands. He is currently We have been awarded funds from the new working at the Centre for Molecular and Biomo- DOE grant that funds the Great Lakes Bioenergy lecular Informatices at the Radboud University Research Center (GLBRC) to develop NMR- Nijmegen Medical Center. based metabolomics support for the project and to carry out related research. We were awarded an News from former lab members: equipment grant for a new NMR spectrometer Ken Prehoda was recently granted tenure console with a cryogenic probe for direct detec- at the University of Oregon. His lab is up to 10 tion of 13C and 15N. Th is system will recycle people now, which he says caused him to stop the magnet from NMRFAM’s 500 MHz spec- micro-managing, because he is squirreled away in trometer without a cryogenic probe. A new high his offi ce submitting papers and grant proposals sensitivity cold probe was installed on the 900 most of the time. We are seeing more of Mike MHz spectrometer this past August. Reily, now that he has joined the NMRFAM External Advisory Board. Mike was recruited Other News: recently by Bristol-Myers Squibb in Princeton. In June, NMRFAM presented a “Protein Structure Determination” workshop. Th is intro- Meetings: ductory workshop exposed participants to the John wisely started 2007 with a trip to Maui steps involved in solving a protein structure from for the Pacifi c Symposium on Biocomputing, data processing through structure calculation and where he presented a talk on “New Bioinformatics refi nement in a series short lectures and hands- Resources for Metabolomics.” From there, John on exercises. Th e workshop was run primarily by traveled to Utah for a Keystone Symposium and NMRFAM staff (Gabriel Cornilescu, Marco then to Italy for an “Advances and Management Tonelli, Anne Lynn Gillian-Daniel, Milo Wes- of NMR in Life Sciences” meeting. After spend- tler, Klaas Hallenga, Hamid Eghbalnia, Arash

40 Bahrami, Eldon Ulrich (BMRB), Nick Reiter won the Biochemistry Graduate Mentoring (Sam Butcher’s group)) and brought in 27 partic- Award for his great work with undergraduates. ipants from throughout the United States. Due Ian has several students working with him col- to the high level of interest, we are holding the lectively referred to as Team Metabolon. workshop again in June of 2008. Anna Füzery received a Vilas Travel Fellowship this year which Milestones: she will use to visit collaborator Larry Vickery’s Congratulations to Sannali Matheson and lab at the University of California-Irvine. As the Joseph Dittli, who were married in July. Joseph temperatures are now in the negative numbers works as a computer programmer at Epic Sys- here, we recommend she go soon. Ian Lewis tems Corporation in Verona, WI.

2007 was a year of many changes. Roum- a set of structural motifs that represent strate- mel Marcia moved on to Duke University as a gies proteins employ to recognize DNA base pair research scientist, where he is working on medi- steps. Stitching the motifs together may provide cal imaging applications with Rebecca Willett. a new way to understand and predict protein- Steve Darnell is working hard to graduate by DNA interactions. Omar Demerdash has been year's end. After presenting his work on predict- working a data mining/machine learning-based ing protein binding hot spots at the ISMB/ECCB model to accurately predict residues that will conference in Vienna, he refocused his eff orts to perturb allostery when mutated. Jennifer Losaw Julie Mitchell validate predicted mutations that improve the and David Dynerman are two new members of Lab binding affi nity between two proteins. Th e pre- the group. Jennifer is a mathematician who will liminary results are very encouraging, and Steve work on multibody protein studies. David has hopes to fi nish these experiments very soon. been working on graphics accelerated versions of Sarah Cunningham has been studying how some of our protein energetic algorithms. We've proteins recognize DNA from a structural and implemented a fast desolvation model and are statistical perspective. By clustering spatial pat- seeing nice speedups compared with previous terns of hydrogen bond networks, she developed implementations.

Th is past year has been a year of changes for the Kiki Chu and Xueqing Liu all presented post- Ntambi Lab. Dr. James Ntambi is currently ers at the conference that were very well received. on a 6-month sabbatical in Uganda, where he Apart from the scintillating scientifi c program, is interested in working with AIDS patients on we participated in a variety of activities, includ- anti-retroviral therapies. Dr. Ntambi is interested ing mountain biking, canoeing, hiking and in obtaining plasma samples for clinical analyses catching up with peers over a pint (or more) of from these patients, many of whom suff er from NH beer. lipodystrophy due to their anti-retroviral treat- As for those of us currently in Madison, Matt James Ntambi ments. continues to feed his fascination with fat. Matt Lab Makoto Miyazaki, a prominent fi xture of and others are using the Cre-loxP system to gen- the Ntambi Lab over the past seven years, recently erate a panel of tissue-specifi c SCD1 knockout left us to take on an Assistant Professor position mice to help us answer "Where in the body does in the Division of Endocrinology, Metabolism SCD1 defi ciency elicit its metabolic eff ects?" He and Diabetes at the University of Colorado and is also planning to begin his home-based S. cer- Health Sciences Center at Denver. While we evisiae fermentation research program. were sad to see him go, we wish Makoto contin- Harini presented her thesis seminar in the ued success at his new post. Department of Nutritional Sciences in Decem- Before Makoto and Dr. Ntambi left Madi- ber and has been wrapping up her studies on son, the Ntambi Lab took a “fi eld trip” to the regulation of SCD1 by dietary fats. She has also Gordon Conference on Molecular and Cellular developed an interest in understanding the role Biology of Lipids at Waterville Valley, NH, in of SCD1 in the skin in regulating energy expen- July. Makoto, Matt Flowers, Harini Sampath, diture and whole body metabolism. She recently

41 returned from a two-week vacation in Vishakap- studied transcriptional regulation of the fatty atnam, a coastal town on the southeastern coast acid synthase gene. His research interests include of India, where her family currently resides. adipocyte diff erentiation, metabolism, and obe- Similarly, Kiki is also trying to fi nish up her sity, and he is currently using rodent knockout studies on deciphering the molecular mecha- models to examine the roles of SCD proteins in nism by which SCD1 defi ciency protects against the growth and development of fat cells. Michael’s elevated plasma triglyceride upon LXR activa- career goal is to eventually run and manage his tion. With the plan to defend her thesis by the own independent fat cell biology lab. end of summer, she is pushing herself to work Chad Paton joined the Lab as a postdoc- hard but, at the same time, remembers to stay toral fellow in July 2007 after a two-year post healthy by getting enough rest and participating doc at the Blood Research Institute in Milwau- in extracurricular activities. kee where he studied coagulation biology. He is Xueqing has been continuing his studies currently investigating the role of SCD in breast on the regulation of SCD1 in infl ammatory cancer and splits his free time between triathlon responses during the past year. Th e research is training, skeet shooting, and bird hunting. now moving on to elucidate the role of liver Another recent addition to the lab is Min- SCD1 in diet-induced infl ammation by using ghui Zhao, who has joined us as a lab techni- liver-specifi c SCD1 knock-out model. Xueqing’s cian. Since starting in January, Minghui has research will provide new insights into the inter- been working on general lab maintenance and play between diet and SCD1 defi ciency in the lab inventory database construction. She has also infl ammatory responses in liver. set up a paperless, database-driven web interface Th e Ntambi Lab has also welcomed several ordering system for the Ntambi Lab. new members to our group this year. Michael We hope that you have enjoyed catching up Griffi n joined the lab as a postdoctoral fellow on recent happenings in the Ntambi Lab. Good in May 2007. Michael received his Ph.D. at luck to you in the upcoming year! Please do stop the University of California, Berkeley, where he in if you are in the neighborhood.

Th e Pike laboratory is entering its 7th year of both enjoy living on the “outskirts” of the big operation in Madison, and I have to say that I city of Madison. have enjoyed every minute of it (well, almost every Dr. Jackie A. Fretz completed her minute). Our group is comprised of eight indi- Ph.D. degree this past August and moved to viduals, four postdocs, three graduate students, Connecticut, where she is currently a postdoc and one undergraduate lab helper and researcher. with Dr. Mark Horowitz at Yale University. Th is group is as highly dedicated a collection of Jackie was interested in osteoclastogenesis, talented individuals as I have ever had the plea- identifi ed novel components of the RANKL Wes Pike sure of working with, and they make coming to activation pathway, among other discoveries, and Lab the laboratory and exploring new things both fun has chosen to continue many aspects of this work and exciting. with Dr. Horowitz. Dr. Lee Ann Short is now in her second year Dr. Mark B. Meyer also successfully com- as a postdoc, having remained in my laboratory pleted his Ph.D. degree during the past summer, following successful completion of her Ph.D. fi nishing a project aimed at understanding how degree in 2006. Lee continues to work on my vitamin D regulates genes involved in calcium favorite transcription factor, the vitamin D recep- homeostasis. Th is work defi ned how the vitamin tor, and has made enormous progress recently in D hormone through its receptor modulates cal- furthering our understanding of how the gene cium ion channel genes TRPV5 and TRPV6, for this receptor is regulated and how the pro- both of which are involved in intestinal and renal tein functions as well. Lee has been instrumental calcium uptake. Mark and his wife Carol have in developing emerging technologies that will also chosen to remain in Madison. Th us, Mark enable us to examine the transcriptional activi- will continue in this laboratory as a postdoc, and ties of very large DNA constructs, as exemplifi ed is now focused on the development and imple- by the vitamin D receptor gene. Both Lee and mentation of methods that will allow us to study her husband Zack live in Sun Prairie, and while gene regulation in greater depth. His talents, not the commute in the winter is sometimes diffi cult, only at the bench, but at the computer as well,

42 have facilitated this laboratory’s whole-scale entre vation, Rob has more recently become involved into novel genomic studies. Mark has a “thing” in our return to defi ning the molecular actions of for hockey, so we pray for continued frozen ice. estrogens and androgens in the skeleton. Recent Dr. Melissa Martowicz joined our laboratory advances in this area have suggested some novel in 2006, having completed a Ph.D. in the labora- opportunities. Rob keeps his energy level high for tory of Dr. Emery Bresnick in the Department of work in this laboratory by lifting weights-lots of Molecular Pharmacology. Melissa is focused upon them. understanding how the RANKL gene is regulated, Katie Bishop also passed her Preliminary and has employed a variety of topical techniques Exam, and now focuses full time on understand- towards that understanding. Interestingly, we are ing how cytokines and other regulatory compo- discovering that many of the principles that we nents operate to regulate the RANKL gene. Like thought were originally unique to this gene may so many projects, one observation led to another be more the norm rather than the exception. and then another, such that her project is now Dr. Seong Min Lee joined the laboratory as a comprised of multiple components. And like so postdoc in September of last year, having arrived many projects, observations we thought would from South Korea with his wife and young be quite simple to solve have turned out to be daughter. He is a great asset to the laboratory, much more complex that originally anticipated. although he is, perhaps too quiet (if that is possi- Katie’s successful completion of Madison’s Triath- ble). Seong Min is currently advancing several of lon Event this past summer suggests that she will the projects that were initiated by Jackie, and has likely have the stamina for this work. We expect also taken on new ones, all focused upon a better Katie to make important discoveries and add new understanding of RANKL induced osteoclast for- insight into her chosen projects. mation. He is currently attempting to identify Paul Goetsch becomes the newest graduate regulatory targets of the osteoclast diff erentiation student member of the laboratory, having just factor NFATc1. Unfortunately, it has been Seong joined in the past month of February. Under the Min’s misfortune to have had to experience one tutelage of Dr. Meyer, however, Paul is rapidly of the most diffi cult winters in Madison in many coming up to speed with respect to the techniques years. Indeed, records for snow fall have been set we employ in the laboratory, and I anticipate this winter. great things from him as well. Paul brings several Rob D. Nerenz passed his Preliminary Exam protein chemistry skills to the laboratory, and his in Biochemistry almost a year ago, and is now a interest in mass spectrometry raises the possibility third year graduate student focused on defi ning that we may be able to advance experimentally diff erential mechanisms whereby hormones regu- our understanding of the role of phosphorylation late human RANKL gene expression. Th e results in vitamin D receptor function. of his initial work were recently published, pro- Finally, last but not least, is Heidi Coy, who viding Rob with his fi rst fi rst-author paper. While is an undergraduate helper and researcher in still working on the “geometry” of RANKL acti- the laboratory. Heidi is a trustworthy and hard- working addition to the laboratory and plays an important facilitating role in everyone’s work. She is currently learning several of the techniques used routinely in the laboratory, and is experienc- ing the thrill of exploring the eff ects of vitamin D on gene regulation in culture cells. She is a great addition to the group. In closing, I must say that I have been blessed with a great group of highly interactive, hard working scientists who are making exciting new discoveries in the area of steroid hormone action. Th anks to the eff orts of each of these individu- als, our funding remains excellent even in these tough times, and I am confi dent that that will continue. Given the interesting observations that we continue to make, I believe that the next few years will be not only productive but exciting.

43 Greetings from our ’85 wing laboratory, where diff usion of GFP and characterize crowding a lot has been going on in the calm-before the and confi nement eff ects in osmotically stressed storm of demolishing the 1950s wing and build- E. coli. Michael is now a postdoc at the Univer- ing the new tower for people in this wing and sity of Washington, Seattle. Jonathan Cannon our medical school biochemistry colleagues. obtained his Ph. D. in Biophysics (’06) for his Steered by senior members Mike Capp, Ruth research into the interactions of denaturants and Saecker, Irina Shkel and me, a near-tidal wave osmolytes (stabilizers) with protein surfaces, and of six graduate students, one postdoc, and three the interpretation or prediction of these eff ects Tom Record undergraduates have fi nished in the last year and in terms of structure. Jonathan is now a post- Lab a half. In the process, they have greatly advanced doc at Case-Western Reserve University. Left our understanding of how E. coli RNA poly- behind, in addition to many lab books and good merase opens promoter DNA to initiate tran- memories, are many papers to write. scription, how solutes and salts aff ect biopolymer In addition to these Ph. D. graduates, three processes including DNA wrapping on protein very talented Biochemistry undergraduates surfaces and coupled folding of protein surface (Kevin Beier, Kate Engel, and Sara Heitkamp) loops on DNA, and how E. coli functions as an fi nished their undergraduate research projects chemical and osmotic system. (on IHF, RNA polymerase, and lac repressor, Carrie Davis (Biochemistry Ph. D. 2007) respectively) and headed for graduate school started this recent wave of Biochemistry gradu- (to Harvard, Berkeley and Yale, respectively). ates; her research used DNA footprinting and Left behind are more good memories and more kinetic studies to characterize the structure and papers to write. function of the extensive wrapping (100 bp) of New Biochemistry graduate students in promoter DNA on RNA polymerase in an early our group include Amanda Drennan from intermediate in the mechanism of forming the Beloit College and Ben Knowles from Wash- transcriptionally-competent open complex. ington State University. Amanda is investigat- Carrie is now studying HIV reverse transcriptase ing eff ects of DNA and polymerase variants on as a postdoc with Stephen Hughes at the National the late steps of open complex formation, and Cancer Institute in Fredrick, Maryland. Kirk Ben is quantifying the eff ects of polyethylene Vander Meulen characterized DNA wrapping glycol (PEG) on protein processes. Continuing for his Biochemistry Ph. D.’07), using Integra- graduate students are Junseock Koh (Biophys- tion Host Factor (IHF) as the protein and fl uores- ics, HU-DNA interactions by FRET and calo- cence (FRET) and titration microcalorimetry as rimetry) and Ted Gries (Biochemistry, RNA techniques. Kirk moved just far enough to be out polymerase-promoter mechanism), as well as of the direct path of construction, to a postdoc undergraduates Brad Nelms, Rob Erdmann with Sam Butcher in the newer building. Recent and Tim Wendorff , all studying solutes or salts, Physical Chemistry Ph. D. graduates are Wayne Ben Strick and Kara Kaplan (both studying Kontur (’06) and Laurel Pegram (’07). Wayne RNA polymerase), and Kevin Metcalf (studying characterized DNA opening and other large- HU). Our creative, dedicated and hard-working scale conformational changes in the steps of open senior members are Ruth Saecker (RNA poly- complex formation by RNA polymerase, and is merase-promoter mechanism and other protein now a Biofuels postdoc across Linden Drive in interactions), Irina Shkel (analysis of GFP dif- Bacteriology with Tim Donohue. Laurel discov- fusion in vivo and salt eff ects on biopolymer ered a straightforward but powerful quantitative processes in vitro), and Mike Capp (solute-bio- method of predicting or interpreting Hofmeis- polymer interactions, solute eff ects on biopoly- ter eff ects of salts on protein processes, using mer processes, and jack of all trades as well as lab model compound data and structural informa- manager). Senior scientist Charles Anderson tion about the protein surface buried or exposed (theory of solute and salt eff ects) transitioned to solvent in the process. Laurel is staying on to emeritus status. My election to the American as a postdoc to continue this very productive Academy of Arts and Sciences and selection as a research. Michael Konopka, a Ph. D. (’06) with fellow of the Biophysical Society honor our col- Jim Weissshaar in Chemistry, stayed for a short lective accomplishments as a lab. postdoc in our lab to use recovery of GFP fl uo- Th anks and best wishes to all, rescence after photobleaching (FRAP) to study Tom 44 Th e Raines lab remains in a steady-state. While plan to get married this summer. some students prepare for “retirement,” others are just starting to explore the interface between Progeny chemistry and biology. Jeremy Johnson and his wife Carol brought Soren Randal Johnson into the world, and Nicky Departures McElfresh and her husband Patrick created Colin. In the last year, four graduate students were Rex Watkins and his wife Natalie are expecting able to defend Ph.D. theses. Jeremy Johnson is their second child. Ron Raines now a postdoctorate at Harvard University. Annie Tam, our former artist-in-residence, is a postdoc- Armchair Quarterback Lab torate at Th e Scripps Research Institute. Luke Daniel Gottlieb has maintained his Fantasy Lavis will continue to use chemistry to “shed Football supremacy by capturing the champion- light” on biology as a Fellow at the Janelia Farm ship yet again, despite claiming to know little Research Campus of the Howard Hughes Medical about American football. Institute. Tom Rutkoski is a postdoctorate with George Phillips in the campus Great Lakes Bio- Armchair Chucker energy Research Center. (Tom had the distinction Ron had his “one shining moment,” winning of receiving the 30th Ph.D. degree awarded to the the UW Biosciences NCAA basketball pool in a group!) Also, former postdoctorate Matt Allen is hard-fought contest. Although picking Kansas now on the faculty at Wayne State University. over Memphis in the fi nal game, he still needed the total-points tie-break to win. Parties ensued, Arrivals and he now has vindication for watching all those We are excited that two graduate and three college basketball games. undergraduate students joined the Raines Lab in 2007: Mike Palte, who is an M.D./Ph.D. student, Current Events and Ben Caes, who is a chemistry student. Jackie Of special note is Greg Ellis being the Hal- Blank and Anthony Cefali have teamed up with loween-costume consultant for the group, with Joe Binder to help develop new cellulosic biofuels. specialties like “Mr. Potato Head.” Jonathan Pua works with Kelly Gorres to study the active-site residues of proyl-4-hydroxylase. Although there has been much turnover in the lab, we still maintain a collegial atmosphere that Couplings fosters creativity in a broad range of research proj- Kelly and John May (Kiessling lab) along ects. Please stop by if you are in town – we always with Margie Borra and Adam Garske (Denu lab) enjoy seeing you!

45 Greetings from the 4th fl oor of the Enzyme joined Bruker as an applications engineer back Institute (EI). We have experienced some turn- in August of ’06. Güneş Bender completed his over since our last report. Steven Mansoorabadi Ph. D. in December of ‘07 and recently joined completed his Ph. D. back in the spring of ’06. the laboratory of another good friend, Steve He is currently a postdoctoral fellow in the lab of Ragsdale at the University of Michigan in Ann our good friend, Ben Liu at UT-Austin. Steve’s Arbor, as a postdoctoral associate. George, Russ artwork made the cover of J. Org. Chem. back in Poyner, and Ann Menefee are presently “hold- August of ’07 to highlight his review article with ing down the fort.” In July of ‘07, Ann, Güneş, George Reed Chris Th ibodeaux and Ben. Paul Sims, who Russ, and George attended the Gordon Research Lab fi nished his Ph. D. in August of ’05, immedi- Conference on B12 that was held in Biddeford, ately took a position as assistant professor in the ME. We met up with former lab member Vahe Chemistry Department at Minot State in North Bandarian (Univ. of Arizona) who made cer- Dakota. Last summer Paul moved to the Depart- tain that no one was “thirsty” following the eve- ment of Chemistry & Biochemistry at the Uni- ning scientifi c sessions. In January ‘08, George versity of Oklahoma in Norman. Todd Larsen traveled with Brian Fox to Ventura, CA for the Gordon Research Conference on Protein Cofactors, Radicals, and Quinones. Th ey met up with former EI researchers and collaborators Squire Booker (Penn State) and Oli Magnus- son (Reykjavik, Iceland). It rained for almost the entire week, but the outstanding meeting Image right shows the electronic structure of was ample compensation for the soggy weather. a radical intermediate Brian and George acquired “the latest” informa- in pyruvate, ferredoxin tion for several of their upcoming lectures in the oxidoreductase Cofactors course.

Comings, comings, and more comings. (Lehigh University, Department of Chemistry). One and a half years have fl own by since we Matt Copeland is a second year graduate student moved into Anant’s former space. In that time our in IPiB who is studying the role of iron in swarm- lab has taken shape and many projects are emerg- ing motility in E. coli in collaboration with Tricia ing. Below is a summary of all of the students in Kiley (Biomolecular Chemistry, UW-Madison) the lab (in alphabetic order) and a brief descrip- and the basis for collective motility in populations tion of their research projects. of cells on surfaces. Matt has emerged as a bud- ding geneticist and is hoping to attend the Cold Doug Weibel Graduate students: Springs Harbor Short Course in Bacterial Genet- Lab Abishek Morali Mohan is a fi rst year student ics this summer. Matt received a training grant in IPiB from Anna University, India. Abi brings from the NIH Biotechnology Training Grant a background in engineering and biology to the Program at UW-Madison in January. Jenna Eun group and is exploring: 1) the mechanics of the is a fi rst-year student in the IPiB program who bacterial cell wall in Escherichia coli; and 2) the graduated in ’07 with a B.S. in Biochemistry mechanism of polar localization in cells. Basu from UW-Madison. Jenna brings a background Bhattacharyya is not a graduate student per se, in biophysics and chemistry to the group and but will be soon. Basu graduated from Biochemis- is developing a technique for creating biofi lms try at UW-Madison (’05) and has managed the lab that makes it possible to understand the role of for two years while working on research projects – surface gradients in their formation. She is also he is an integral member of the team and we will working on the discovery and characterization be sad to see him leave for graduate school. Basu of small molecules that bind to cytoskeletal pro- is studying the transport of nanoparticles across teins in bacteria. Hannah Tuson is a second year the bacterial cell wall to lay the foundation for student in IPiB who is studying how cells sense a new ultra-resolution imaging technique we are surfaces and the physical, chemical, and genetic developing for studying sub-cellular organization mechanisms that regulate diff erentiation of E. in bacteria with our collaborator, Dmitri Vezenov coli into the swarming phenotype. Hannah is a 46 trainee of the NIH Molecular Bioscience Train- He recently received a Hilldale Research Fellow- ing Grant; she will attend the Physiology Course ship. Joseph Molenda is a junior who has been at the Marine Biological Labs at Woods Hole this in the group for over one year. Joe is studying summer. Abbey Vangeloff is a fi rst year IPiB stu- ‘synthetic’ shape transitions in Neisseria in col- dent who received a B.S. in chemistry from Duke laboration with Joe Dillard’s group (Med. Micro., University and spent a subsequent year studying UW-Madison). He received a Hilldale Research protein/protein interactions. Abbey’s research Fellowship in 2007. Tanner Peelen is a sopho- focuses on the bacterial cytoskeleton. In one of more majoring in Biochem who joined the lab her projects—a collaboration with Zemer Gitai last semester. Tanner’s project involves optimizing (Molecular Biology, Princeton)—Abbey is using semiconductor quantum dots to transform bacte- a genome-wide screen in Caulobacter to discover rial cells. Peter ValdenVelder is not yet an under- and study small molecules-cytoskeletal protein graduate at UW-Madison but he acts the part. interactions. Abbey received a training grant from Peter has been working in the lab for the past year the NIH Biotechnology Training Grant Program – he recently graduated from West High School at UW-Madison in January. Th ese students are and will be an undergrad at UW-Madison this outstanding, motivated, creative, and fun to work coming year. Peter’s project is exploring swarm- with. ing in Vibrio. We are hoping Peter will stay with us in the coming years. Undergraduate students: Charles Burns is a junior majoring in Bio- PI: chemistry and Spanish who has been in the lab In addition to teaching, research, and advis- for over one year. Charlie is studying the con- ing, I am involved in several outreach projects both nection between cis-platin and the prokaryotic on and off campus. In 2007, Aseem Ansari, Mike analog of eukaryotic tubulin, FtsZ, in the pro- Sussman, Franco Cerrina (Electrical Engineering), cess of cell fi lamentation. He recently received a and I co-founded the UW-Madison International Hilldale Research Fellowship. Mariko Hasebe is Genetically Engineered Machines (iGEM) Com- a senior majoring in Biochem who has been in petition Team). Th e team introduces undergradu- the lab since Fall 2007 and is developing a tech- ate students in the life sciences and engineering nique for measuring the Young’s modulus of the to interdisciplinary research in synthetic biology bacterial cell wall. Mariko recently received the and culminates in a competition held at MIT in Mary Shine Peterson Award. Sean McMaster is a November. Our fi rst year was a success and we are sophomore majoring in Biochemistry and Math- actively organizing the 2008 team. ematics who has been in the group for over one In November, Basu and I co-founded an out- year now. Sean’s project is to develop a chemi- reach program to introduce local K-12 students cally defi ned minimal medium that supports cell to optical microscopy to help them explore ‘the swarming. Sean is the 2007 ‘Steenbock Stairmas- microworld.’ MicroExplorers is a collaborative ter’ and holds the group stair-climbing record. eff ort that combines the expertise of a half-dozen young microscopy-oriented scientists across campus who share an interest in educational out- reach (www.MicroExplorers.org). Th e program is made possible by the commercial availability of relatively inexpensive digital optics. We have already carried out pilot projects with local K-5 students and are currently in the process of rais- ing money to purchase more microscopes. 2007 saw the departure of two students: Corinne Lipscomb is a Chemistry gradu- ate student who worked in the group for a year and left in December. Tae Won “Bryce” Kim is a junior who spent the Fall semester with us while working on a research project for Bio 152. We wish you a wonderful 2008 and look forward to keeping you informed of our future progress. 47 As I write this newsletter this year, we sit in directions. Andrew Prigge and Leah Gross, 9,000 feet of snow and ice, and await the two undergrads, have joined in developing new next ice age, despite Greenland’s thaw. In our ways to fl y through PUF–RNA space. igloos, we continue to focus on how mRNAs Amy Cooke, a CMB student, has been are controlled, how proteins and RNAs fi nd using frog oocytes to understand how mRNAs one another, and the many ways in which in eggs and embryos are controlled; a long- biology uses RNA. term issue here is to try to understand to what extent the mechanisms seen in yeast and Marv Wickens Continuing… embryos are really the same, and what features Lab JJ Chritton has passed her prelim with of each are idiosyncratic. A paper is becoming fl ying colors and convinced her committee visible on the horizon. that she could “do three complete experiments Labib Rouhana and Jae Eun Kwak both a day without breaking a sweat” which of defended their theses at the end of 2007. Labib, course led them to suggest that “she should do who continues to work on new regulators and six experiments a day so that she sweats.” We new ways to detect RNA-protein interactions hope she will soon gain the acclaim of review- in vivo, is planning a radical change of setting, ers with equal aridity. She is working on how and has arranged a post-doc with Dr. Agata in one class of repressor proteins work, using Kyoto, Japan. He anticipates working on how cell-free systems that parallel in vivo studies mRNA control contributes to regeneration. in yeast, and has made great headway. Aaron Jae Eun has fi ngers in many pies. Right now, Goldstrohm, a post-doc, after a fl urry of she is juggling work on the role of mRNA con- papers and job interviews, is returning to the trol in memory – some major breakthroughs bench to fi gure out which proteins talk to a there in which she identifi ed an enzyme criti- central group of regulators (the PUF proteins, cal for long-term memory in particular – with for the avocados among you), as a means to studies of a new group of enzymes that add understand how they repress translation and poly(U) rather than poly(A) to RNAs. Th e cause mRNAs to be destroyed. Along the way, memory studies have benefi ted immeasurably Aaron has written a review of deadenylases and from a collaboration with Jerry Yin in Genet- another of how to study poly(A) removal, both ics, who in a triumph of inbreeding, was in published in prominent journals. Th ese grew fact Bill Reznikoff ’s grad student when Marv out of his studies with Brad Hook and Daniel fi rst arrived in Madison. Jacque Baca, is fi gur- Seay. Brad has moved on to Promega (a local ing out how protein and microRNA mecha- Biotech company) where he thrives develop- nisms of repression may interface in the C. ing and analyzing new products and applica- elegans germline. tions. Rumor has it that he is soon to make an appearance at a lab bench here again – most Moving on… welcome. Daniel Seay, graduate student here and Laura Opperman, soon to defend her a man of exothermic life style, exuding ener- thesis, has been working on how PUF proteins getic radiation in many forms, has moved on fi nd their RNA targets. Th is work has gotten to Rockefeller as a post-doc with Mike Young, an elating boost through our collaboration with studying rhythms in fl ies. My impression is Dr. Traci Hall (North Carolina) who has deter- that he really likes New York, but is looking mined the structure that goes along with Lau- forward to being done with his work from ra’s earlier molecular genetics. Once she fi nishes here. He continues to wrap up a very interest- collecting the data and writing ten additional ing group of studies on a new form of regula- papers, she will be moving on to Scott Ken- tion, for which he was incessantly teased here nedy’s lab on campus to study RNAi. Craig at fi rst – kudos to him. Stumpf, another student, is soon to defend his PhD as well; and will be staying for a while Coming back…. after to explore PUFinalia in new ways. Craig Natascha Buter, who had received a Mas- and Laura have been joined in this endeavor by ter’s in the lab a few years ago, has returned Yvonne Koh, a graduate student, whose work and now takes care of us all in maintenance, in short order revealed some new surprises in ordering, etc. It’s a great pleasure to have her recognition, and now is moving off in new back to lend her energy, insight and great

48 spirit. Laurel Bessey, an undergrad, continues who has the great wisdom to be oblivious to to pour plates and help with lab maintenance. deadlines. Dave Bernstein, in Washington and still involved in science policy, married A few alumni…. this last year and appears from a distance to be Omissions are inevitable, but let me men- thriving. From the words we exchange, Pete tion a few small developments that relate to Wigley, down under, seems to be entirely alumni with whom I have had some sort of unchanged, though I suspect he now weighs special contact in the last year. It was delight- 340 pounds, carries a machete and smokes ful to have a visit from Niki Gray and Kris cognac-laced cigars (but still has those shorts). Dickson, in a birthday celebration in Madi- My apologies to the many of you that I have son, and to meet their Signifi cant Others and been unable to mention. hear what they are up to – namely, science Marv is graduating, defending, writing in Edinburgh (Niki) and Big Shot editing in grants and letters, and greatly enjoying science Boston (Kris). Judith and I have had the good and the people in the lab, however bizarre their fortune to see a bit more of Dave Zarkower behavior becomes (you have no idea). Carol and Vivian Bardwell, both on the faculty at continues to keep him on track. Marv enjoys a University of Minnesota, now that Zach goes temporary trip to the third person, as it makes to college nearby. It's always a treat to see them him feel so athletic, as in “He really loves to both. Scott Ballantyne, at UW River Falls, step back behind the three point line and write continues to have creative ideas about how the Abstract as he drives to the hoop and slams regulation works, and is always great to hear the Discussion through the net.” But shock- from. Had a chance to visit Sunnie Th omp- ing himself back to fi rst-person reality…. I am son in Birmingham last year, and it was a doing fi ne, or so I think, with no increased ath- special pleasure to see how happy she was in leticism. Our son, Zach, is off at Macalester, her new professorial state. Cameron Luitjens, where as the British say, the world is his oyster, now a lawyer raking in the billable hours, was and he is devouring them on the half-shell recently accosted with an email from me about by the dozen. Chemistry, mathematics, com- work he did 10 or more years ago, which we puter science and writing are off ered up with are thinking about trying to write up at last, horseradish, lemon and dipping sauce. Chil- since it keeps getting asked for. Th is will really dren, whether biological or scientifi c, whether challenge the long-term memory bank. Mike newborn or middle aged, are one of the great Sheets and Catherine Fox, both on the faculty graces of my life, and I thank you all. Come by here, are buoyed by their delightful son, Max, sometime. You will always be welcome.

49 Faculty Email & Telephone Numbers Rick Amasino ...... [email protected] ...... 608/265-2170 Aseem Ansari ...... [email protected] ...... 608/265-4690 Alan Attie ...... [email protected] ...... 608/262-1372 If you have questions or information Sebastian Bednarek...... [email protected]...... 608/263-0309 please feel free to contact us. Sam Butcher ...... [email protected] ...... 608/263-3890 http://www.biochem.wisc.edu Margaret Clagett-Dame ... [email protected]...... 608/262-3450 Mo Cleland ...... [email protected] ...... 608/262-1373 Department of Biochemistry Mike Cox ...... [email protected] ...... 608/262-1181 University of Wisconsin–Madison Betty Craig ...... [email protected] ...... 608/263-7105 433 Babcock Drive Hector DeLuca ...... [email protected] ...... 608/262-1620 Madison, WI 53706-1544 USA Brian Fox ...... [email protected] ...... 608/262-9708 Paul Friesen ...... [email protected] ...... 608/262-7774 Phone: 608/262-3040 Colleen Hayes ...... [email protected]...... 608/263-6387 FAX: 608/262-3453 Hazel Holden ...... [email protected]. . . . 608/262-4988 Ross Inman ...... [email protected] ...... 608/262-9881 Change of Address, Information, Laura Kiessling ...... [email protected]...... 608/262-0541 and General Inquiries Judith Kimble ...... [email protected] ...... 608/262-6188 Bob Landick ...... [email protected] ...... 608/265-8475 Cheryl Adams Kadera John Markley ...... [email protected] ...... 608/263-9349 (608) 262-9835 Tom Martin ...... [email protected]...... 608/263-2427 E-mail: [email protected] Julie Mitchell ...... [email protected] ...... 608/263-6819 Dave Nelson...... [email protected] ...... 608/263-6879 James Ntambi ...... [email protected] ...... 608/265-3700 IPiB Graduate Program Ann Palmenberg ...... [email protected]...... 608/262-7519 (Information and Applications) George Phillips ...... [email protected] ...... 608/263-6142 Flavia Arana (608) 265-2281 Wes Pike ...... [email protected] ...... 608/262-8229 Ron Raines ...... [email protected] ...... 608/262-8588 E-mail: graduateadmissions@bio- Ivan Rayment ...... [email protected] . . .608/262-0437 chem.wisc.edu Tom Record ...... [email protected] ...... 608/262-5332 George Reed...... [email protected]...... 608/262-0509 Mike Sussman ...... [email protected] ...... 608/262-8608 Undergraduate Program/Internships Doug Weibel ...... [email protected] ...... 608/890-1342 Dan Barnish (608) 265-9846 Marvin Wickens ...... [email protected]...... 608/262-8007 E-mail: undergraduateprogram@bio- Chris Wiese ...... [email protected]...... 608/263-7608 chem.wisc.edu Emeritus Julius Adler ...... [email protected] ...... 608/262-3693 Gifts/Donations Laurens Anderson ...... [email protected]...... 608/262-3041 Robert Burris ...... [email protected] ...... 608/262-3042 Please use the form at the right Perry Frey ...... [email protected] ...... 608/262-0055 or go online to: Alfred E. Harper ...... [email protected] www.uwfoundation.wisc.edu Paul J. Kaesberg ...... 608/262-2205 You may also contact the Chair: Henry Lardy ...... [email protected] ...... 608/262-3372 Bill Reznikoff ...... [email protected] ...... Betty Craig Roland R. Rueckert ...... [email protected]...... 608/262-6949 (608) 262-3040 Heinrich K. Schnoes ...... 608/262-0650 E-mail: [email protected] John W. Suttie ...... [email protected]...... 608/262-2247

Friends, alumni and colleagues... Please visit our Biochemistry Alumni Forum! Where you can: • Contact your old friends • Find your old labmates • Bless or chastise the chair • Arrange a meeting • Give us advice • Connect Visit https://www.biochem.wisc.edu/forum and click on the Alumni forum! 5050 Donors to Biochemistry Funds in 2007 Ms. Marian T. Anderson Dr. David E. Hamer Mr. John Chase Pirnstill Dr. Mark A. Ator Ms. Sylvia A. Hatfi eld Dr. Mark R. Pope Dr. Walter M. Barker Dr. David A. Haugen Ms. Kathryn L. Prosser Dr. Kathleen Ann Basmadjian Prof. Robert P. Hausinger and Prof. Gregory D. Reinhart Dr. Wendy A. Bedale Ms. Susan L. Kalvonjian Ms. Alice V. Rohde Dr. and Mrs. Raymond E. Benenson Dr. Herbert R. Heinicke Dr. and Mrs. Michael C. Roskos Prof. Norlin J. Benevenga Prof. Mark A. Hermodson Mr. and Mrs. Dale T. Schartner Dr. Duane A. Benton Mr. Kazuko K. Hood Dr. Frederick J. Schendel Mr. Luke T. Bergerud Ms. Rachel C. Houseman Dr. Saul A. Schepartz Dr. Bijoy K. Bhuyan Dr. Chung L. Huang Dr. and Mrs. Charles F. Shuler Prof. James T. Bradley Dr. Th omas D. Huggett Prof. James D. Shull Mr. Joe M. Braun Dr. and Mrs. William T. Jackson Dr. Margaret Shupnik Dr. and Mrs. William E. Brown Mr. Michael C. Janasik Dr. Donald J. Siehr Dr. Jeff rey L. Browning Ms. Heidi Marie Kirkpatrick Drs. David P. and Barbara L. W. Silva, Jr. Prof. George E. Bunce Dr. Donald A. Kita Dr. Th omas J. Skatrud Ms. Melissa F. Cain Mr. Kevin J. Kleinfeld Dr. Bryan D. Smith Mr. James A. Campbell Ms. Anita J. Koerner Prof. and Mrs. Frederick G. Smith Dr. Carolyn A. Campen Dr. Martin F. Kovacs, Jr. Mr. Ward W. Smith and Dr. Douglas B. Chapman Dr. and Mrs. Mei-Chang Kuo Dr. Cheryl A. Janson Mr. and Mrs. Tommy Clary Prof. David O. Lambeth Dr. Pari D. N. Spolter Dr. and Mrs. Anthony H. Conner Mr. and Mrs. Joseph T. Lawton Prof. and Mrs. Fredrick Stormshak Dr. Scott A. Cooper Dr. William L. Leoschke Dr. Joey M. Studts Mr. Brett A. Dieter Mr. and Mrs. William A. Linton Dr. Robert E. Stutz Prof. and Mrs. Lawrence B. Dumas, Jr. Dr. Gerald Litwack Dr. Duane A. Tewksbury Dr. Leo A. Ehrhart Ms. Jennifer M. Loeb Ms. Nancy Torbet Mr. Vincenzo Franco and Dr. Arnold S. Loo Dr. Douglas E. Vollrath Dr. Barbara Gerratana Mr. Bryan D. Marks Mr. Dmitriy Vinarov Dr. Matthew T. Gall Dr. William D. Maxon III Dr. Th eodore R. Watson Dr. and Mrs. Maurice Green Prof. Kelly E. Mayo Dr. William W. Wells Mr. David W. Gregg Dr. John E. Mazuski Mr. Steve R. West and Mr. and Mrs. Kurt A. A. Grunwald Dr. and Mrs. Kevin O'Connell Ms. Julie Ann Waterbury Prof. Sandra K. Grunwald Ms. Linda J. O'Gara Mr. and Mrs. Norman E. Wideburg Prof. Phalguni Gupta Dr. Mary S. Ozers Dr. Todd A. Winters Dr. Glen E. Gutzke Dr. Mark A. Pallansch Prof. Linda M. Hall Prof. George N. Phillips, Jr.

Department of Biochemistry Fund BCHEM

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