New Design for Biochemistry Phase II

For friends of the Department of Biochemistry at the University of Wisconsin–Madison

I am pleased to send you greet- Biochemistry, plus the Ag Journalism building. At ings from the Biochemistry the time, historical preservation was limited to the Department. In the second 1912 building, which was slated to become office newsletter under my watch, space. The Curry murals in the 1937 wing were to we (being Marv Wickens et be moved to new quarters in the 1912 wing. The al.) have changed the format a Ag Journalism building was viewed as suboptimal bit, bringing you more of the and structurally unsuitable for most uses. exciting science going on in The situation has changed dramatically in the From the Chair the department, as well as the interim. About 18 months ago, the entire west Betty Craig “news” to keep you abreast of side of Henry Mall, as well as all of the 1912 and your friends and colleagues. I 1937 wings facing University Avenue, was listed hope you approve, and we welcome com- as a National Historic District. The Ag Journal- ments and suggestions to make the Biochem- ism building was determined to be in better shape istry Newsletter both informative and fun. structurally than we had thought, and the state and university have been reviewing the history of our Biochemistry Phase II Biostar Building Project little neighborhood. The west side of Henry Mall “Challenges and opportunities” is an expression is actually one of the few districts on campus that commonly used these days. Although I am not par- remains true to the original campus plans. A con- ticularly fond of this phrase, I do think it charac- sensus emerged that the preservation of the heri- terizes quite well the Biochemistry Phase II Biostar tage of the district should be an important goal of Building Project, now in an active design phase. The the project, as it was in the best interests of the scope of the project, conceived over a decade ago, department, the university, and the state. is broad, encompassing laboratory space to house The architectural team from Flad and Associ- both Biochemistry faculty (e.g., the FTEs in the ates have come up with a creative design that not Enzyme Institute) and the Biomolecular Chemis- only preserves the history of the older buildings try Department; special facilities, such as chemical (and Elmer, the elm tree), but puts even the older synthesis suites; a large vivarium; and a great deal building space to exceedingly good use in ways that of much-needed classroom and teaching laboratory will invigorate Biochemistry’s teaching program. space. An architectural study completed in 1997 In effect, the 1912 and 1937 wings will become envisioned a building that would take up the foot- a dedicated teaching complex, with new auditori- print defined by the 1937 and 1956 wings of old ums, classrooms, teaching labs, a student lounge, New design for Biochemistry Phase II - "Inspired by the past, building for the future" and some office space in support of the teach- to raise the necessary funds and I hope when I ing effort. The new research tower will be built write you a year from now I can report that we on a footprint that includes the 1956 wing, have broken ground for Biochemistry Phase II. the alley between 1956 and Ag Journalism, We are all truly excited about the project, as it and the animal rooms and auditorium south will provide state of the art research facilities of the 1985 wing. The new structure will abut, for all Biochemistry faculty, while preserving and incorporate into the design, the old Ag our history. Journalism building. This research tower will house the 20-24 research labs, animal facilities, Other updates conference rooms and state of the art chemical I am pleased to report that our new IPiB (Inte- synthesis suites. A new corridor will be created grated Program in Biochemistry) graduate between the 1912/1937 complex and the new program has gone through all of the admin- research tower, facilitating pedestrian traffic in istrative hoops and is now official. In reality this part of campus. we have been acting like it was official for the past year, recruiting together this spring with the faculty of the Department of Biomolecular Chemistry, for what has become our first IPiB class. Ivan Rayment has taken on the job of 1985 Biochem being chair of the IPiB steering committee and 2010 is busy smoothing the road of integration of Research the two graduate programs into one. Biochem Addition, 1998 Thisyear we are pleased to welcome Doug Weibel into the department as a new Assistant Professor. Doug, who has his lab on the fourth floor of the Biochemistry Addition, comes to us 2010 from Harvard Medical School as a cluster hire Teaching in chemical biology. Learn more about Doug Henry and his research on page 4. While welcoming Mall new people into the department, we also need to say goodbye to Bill Reznikoff(see page 10) who, come July 1, will retire after 37 years as a University Avenue Biochemistry faculty member. We are all sorry to see him go. We wish him all the best, and are The plan is ambitious, and will enable the glad to know that he will continue his science, department to enhance its research and teach- but his lab will be on Cape Cod, rather than ing missions over the next decades. The added next to Lake Mendota. cost to renovate the older buildings and the high Our good friend and jack-of-all-trades, Al rate of inflation of construction costs over the Jones (see page 5) is also retiring after many past 2-3 years has left us with a gap in funding great years with us and we wish him well. estimated to be about 12 million dollars out I hope you all a happy and productive year. of the total budget of 117 million dollars for Remember, we are happy to hear from you the project. We are embarking on a campaign anytime, and visit us when you can.

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]

Links Between Obesity and Diabetes by Professor Alan Attie Although most people with type 2 diabetes are (PDGF), a protein that plays an important role obese, most obese people do not develop diabe- in the formation of the vasculature. Cells requir- tes. This dichotomy has inspired us to ask: what ing new vasculature produce vascular endothelial are the genetic differences between people who are growth factor (VEGF), which recruits endo- susceptible to obesity-induced diabetes and those thelial cells to the tissue. Endothelial cells form who are resistant? We also want to identify the tubes, the precursors of blood vessels. They also pathways that trigger the transition to diabetes. produce PDGF, which recruits pericytes (a cell Obese people are insulin-resistant, meaning resembling a smooth muscle cell) to coat the that their cells do not respond fully to normal basolateral side of the vessel. insulin levels. They usually compensate for insu- Mice with the diabetogenic allele of SorCS1 lin-resistance by producing more insulin. This can have vascular abnormalities, while their congenic occur by increasing the insulin secretion from each counterparts do not. To corroborate these find- pancreatic beta cell and/or through the expansion ings, we have turned to zebrafish, another ver- of beta cell mass. However, in type 2 diabetes, tebrate with powerful genetics: zebrafish with this compensatory insulin response is inadequate reduced SorCS1-activity do indeed have dramatic and the gap between demand for insulin and the vascular abnormalities. supply of insulin leads to diabetes. If the gene really is critical in the onset of diabetes in people, we might be able to see that Identifying a new gene in natural human populations. In collaboration We have reproduced the obesity/diabetes dichot- with groups in Los Angeles and San Antonio, we omy in mice. We study two mouse strains that have found that variation in the SorCS1 gene is have been made obese using a mutation that dis- associated with diabetes in Mexican-Americans. rupts the normal suppression of appetite; the two Other groups are determining whether or not this strains differ in their susceptibility to diabetes. To gene is involved in diabetes in other populations. identify the key genes responsible, we mapped several genes that control glucose and insulin Dieting and diabetes levels. This past year, we positionally cloned one Another route to understanding the onset of dia- of these. betes has come from analyses of mRNAs present The gene is SorCS1, a member of the vacu- in obese vs normal mice. DNA microarray tech- olar protein sorting-10 (vps10) gene family. The nology allows one to survey the entire popula- protein binds to platelet-derived growth factor tions of mRNAs in a cell or tissue. Using that approach, we discovered that the cholecystokinin (CCK) gene is massively upregulated in beta cells of the pancreas obtained from obese mice. What makes this interesting is that our studies also suggest that CCK is a mitogen for those same beta cells. Thus, CCK appears to be an autocrine regulator of the beta cell expansion that occurs when an animal is insulin-resistant and obese.

Relevant publications Lan, H. Chen, M., Byers, J.E., Yandell, B.S., Stapelton, D.S., Mata, C.M., Mui, E.T., Flowers, M.T., Scheuler, K.L., Manly, K.F., Williams, R.W., Kendziorski, C.M., Attie, A.D. (2006) Combined expression trait correlations and expression quantative trait locus mapping. PLoS Genet- ics 2:52-61. Clee, S.M., Yandell, B.S., Schueler, K.M., Rabaglia, M.E., Richards, O.C., Raines, S.M., Kabara, E.A., Klass, D.M., Stapleton, D.S., Gray-Keller, M.P., Boronenkov, I., Raess, P.W., Flowers, M.T., and Attie, A.D. (2006) Positional cloning of a type 2 diabetes quanitative trait locus. Nature Genet- ics 38, 688-693. Clee, S.M. and Attie, A.D. (2007) The genetic landscape of type 2 diabetes in mice. Endocrine Rev. 28,48-83. Notes From a New Faculty Member: by Professor Doug Weibel When asked what first drew them to science, As an undergrad I worked with C. Dale chemists most often cite a youthful encoun- Poulter on research projects in isoprene bio- ter with a chemistry set. My first experiences synthesis. In my junior year I sweet-talked with chemistry and science, however, were my way into taking several graduate courses quite a bit different. They grew out of my and ended up in an ‘industrial strength’ childhood interest in blowing things up. I class on enzyme mechanisms and kinetics like to think that my early fascination with in which we read a ream of papers by Mo explosives eventually paid off. Cleland and Perry Frey. It is an honor to As a teenager my scientific interests now find myself a colleague of these two abruptly shifted as I started working in pioneers in enzymology. I graduated from my father’s lab and was introduced to bio- the University of Utah with a degree in chemistry. One of the first experiments I chemistry and spent a year in Japan on a did in the lab involved a large-scale lipase- Fulbright working on a project in organo- catalyzed hydrolysis of a butyric acid ester metallic chemistry with Yoshinori Yama- to butyrate, which I accidentally spilled moto. Much of my free time in Japan was on myself. Chemists affectionately refer to occupied trying to comprehend how little butyric acid as ‘essence of barf’ and it is— grammar I had actually learned in the Japa- unfortunately—an odor that is notoriously nese classes I had taken (namake mono!). difficult to remove once it comes in contact After Japan, Gina and I married and with the skin. This occasion left a strong moved to Ithaca where we both attended impression on my memory, and undoubt- graduate school at Cornell. I worked with edly, the memory of my family and friends Jerry Meinwald on projects in organic chem- as well. istry and then shifted gears and accepted a Chemistry runs in my family. My older postdoctoral position with George White- brother is a physical chemist and my father a sides at Harvard where I worked on proj- physical organic chemist turned biochemist. ects in microbiology, mammalian biology, It was with great effort that I suppressed any organic and surface chemistry, and materi- serious interest in chemistry as a teenager to als science and engineering. (Below) Rod-shaped bacteria can be manip- avoid following in their footsteps. However, At UW-Madison I am in the process ulated into 'unnatural' shapes by control- chemistry captured and held my interest in of building an interdisciplinary group of ling the geometry of their environment during growth. The image shows donut- science and I followed my brother’s encour- biochemists, biologists, chemists, and engi- shaped compartments (background) in aging lead to join him at the University of neers interested in studying the molecular which spiral shaped cells of E. coli were Utah where he was a graduate student. While basis of physiology and behavior of bacteria. grown (foreground and image inset). This experiment leaves us questioning how cells there I fell in love with Gina who was—you We take advantage of the unique capabilities control their shape at the molecular level. guessed it—a lovely young chemist. that each of these areas offers and combine them to develop new tools for dissecting the structure and interactions of cells of bacteria. Bacteria were the model organisms for the development of molecular biology and genetics; they became our foundation for understanding fundamental biochemical processes that occur in prokaryotic and eukaryotic cells. Remarkably, we still understand little about the structure and general physiology of bacteria, yet the mechanisms by which they differentiate into a variety of different phenotypes and organize into multicellular structures are relevant to ecology and biomedicine. Our interest in the behavior of bacteria is largely based on the pio- neering work of Julius Adler who changed the way we think about sensory transduc- tion in microorganisms. As part of the Chemical Biology Cluster at Madi- mechanical) basis for differentiation of cells on son, I am looking for opportunities to apply our surfaces, and the coordination of the motility of interest in chemistry, biology, and engineering to cells on surfaces. The results of these projects will develop a detailed understanding of the biochem- find application in several areas of biomedicine. istry in bacteria. Our initial projects are focused In addition to research, I bring to Madison on understanding how cell shape in bacteria a deep interest in both teaching and educational is controlled, the physical and molecular (and outreach. I have been posing as an undergrad in several biochemistry courses at UW-Madison to get a feel for the teaching styles in the department and am impressed with the high standards of teaching. All scientists have a scientific family tree through which they can trace their roots. I have had several outstanding mentors—Dale, Yoshi, Jerry, and George—through which I can trace my scientific genealogy. In addition to being a part of a scientific ‘family’, Gina and I have three wonderful and creative young children: Xander (age 6), Guy (age 3), and Zoe (age 1). My children constantly remind me—through their actions—that what is most fun in life is the discovery of something you love and a creative and

(Above) An array of gold microelectrodes fabricated on a glass wafer used to isolate and array focused way of approaching it. I strive to bring bacteria for biophysical experiments using epifluorescence microscopy. The very thin lines are these principles to science. And wait to hear the electrodes and the rectangles are contact pads that make it possible for us to apply a potential/ explosions from our basement as our kids grow current across a specific electrode. up and discover chemistry.

Al Jones Retires!!! For longer than many of us have even known the Al has been a key person in Biochemistry for department (let alone been in it), Al Jones has many years. His pleasant ways, sense of humor, been at its heart, making things work. And now and willingness to help out will be greatly missed – hard to believe – Al is retiring! Perhaps there by us all. Good luck Al, and congratulations on really are no eternal truths – but Al is about as your retirement! close as you can come. After 28 years at the Department of Bio- chemistry and the University of Wisconsin, Al Jones has decided to spend more time at home. Al worked in many areas of the department, from animal care, the shops and maintenance, to the storeroom, and helping out whereever he was asked. He always was willing to lend a hand and so got to know, and help, almost everyone in the department. What is more, he did all these things with good spirit. Al likes to say he has a roofers union card, “which pretty much covers everything”. You may not know it, but in addition to everything he did here, after Al got home from work, he would go over to his brother-in-law’s 200+ acre farm, just across the bridge in Prairie du Sac. He lent a hand with everything from planting, to mending fences, ear- tagging heifers and turning bulls into steers! Many a good story came of that! HHMI in the Classroom by Professor Rick Amasino be grown in a school year. Our first attempt was to use Arabidopsis, a common experimental model for plants. Although we had some success, Arabidopsis does have some draw- backs. For example, the seed is too small size to be planted individually by hand, and the small size of the flowers makes it difficult to cross- pollinate. Fortunately, a classroom model, FastPlants (a variety of Brassica rapa), has been developed by Paul Williams at the University of Wisconsin (see http://www.fastplants.org/). FastPlants are in the same family as Arabidopsis (Brassicaceae) and, like Arabidopsis, have a rapid life cycle relative to other plants. Some of the desirable features of rapid-cycling B. rapa relative to Arabidopsis are shown in Figure 1. About 400 rapid-cycling The Howard Hughes Medical Institute has a pro- B. rapa thrive in a 2 by 4 foot space under four gram for faculty who desire to promote science 32 watt fluorescent bulbs. And a major advan- education (http://www.hhmi.org/research/pro- tage is that rapid-cycling B. rapa is already well fessors/), and I was asked to discuss our plans for established in classrooms: it has been estimated a recent award we received from this program. that FastPlants are used by as many as 10 mil- For many years, I have been exploring models lion students each year, and 70,000 teachers have to teach classical, molecular, developmental and been trained in their use (http://www.news. biochemical genetics in K-12 and undergraduate wisc.edu/7728.html). classrooms. In many respects, the ideal models However, the existing FastPlants stocks have already exist in the fruitfly Drosophila and the a significant drawback which limits their develop- nematode C. elegans. But most teachers do not ment as a genetic model – they are not self com- have sufficient technical skill or the equipment patible. Without self compatibility, an enormous (microscopes, facilities for media preparation, number of sibling “matings” would be required etc.) for implementation of these models. Plants to find homozygous recessive mutants. Thus I offer a simple alternative: growing plants requires began a breeding program to introduce self com- little technical skill, equipment or effort, and patibility into rapid-cycling B. rapa. The chal- stocks of mutants (i.e., seeds) are simple to store lenge was to overcome the inbreeding depression and organize. Thus I have focused on developing which often results from the inbreeding of plants plant models for classroom use. that normally are obligate outcrossers. After two years of breeding, I developed several robust, self- Ready for classroom genetics compatible lines, and Scott Woody (photo right) A key feature of a plant model is that it have a has joined me in the effort to use these lines for rapid life cycle so that several generations can teaching genetics.

Comparison of flower and seed size between Arabidopsis and rapid-cyclingB. rapa.

Initial mutants be treated with gibberellin to distinguish mutants Our first goal is to work out the parameters for defective in synthesis (restored to a normal phe- creating a mutant production stream. We then notype) from those defective in sensing (no will assemble teams of undergraduates to keep response to hormone treatment). Furthermore, this stream flowing at a rapid rate. The teams treatment of a collection of mutants that have will be screening for mutants with educationally lesions at various stages of the synthetic pathway useful phenotypes, characterizing the mutants, with gibberellin precursors will reveal that fewer and developing classroom exercises based on mutants will be restored to a normal phenotype as these mutants. For example, Scott recently found one treats with precursors earlier in the pathway, several mutations that result in albino plants. illustrating the order in which the genes (and the Such mutants provide a simple example of a enzymes they encode) act in the pathway. deleterious recessive mutation that prevents sur- Another goal is to develop tools for learning vival to maturity (a nice segue to a discussion of molecular genetics. Gene mapping using DNA topics from lethal mutations to photosynthesis). sequence polymorphisms (a.k.a. “markers”) is an Students can be given seed from a heterozygous important tool in wide use from plant breeding parent that germinates into seedlings that reveal to tracking and cloning loci involved in human a simple 3:1 segregation ratio of green to white disease. To enable the use of such gene map- plants. Interested students can consider how ping tools in our system, I started the breeding to determine the genotypes of the 3/4 of the program with several polymorphic parents, and plants that are green by saving their seed (most selected several self-compatible lines that are poly- of the green plants will produce offspring that morphic relative to each other. Thus, mutants in segregate albinos). This is a great K-12 lesson one line can be crossed to a polymorphic line and because students will need to work back from the mutant locus can be mapped relative to DNA observation to a model. markers in a resulting F2 population. Fortunately, Another example: dwarf mutants provide a we will not have to develop markers that detect great tool to teach biochemical genetics. DNA sequence polymorphisms single-handedly: Many dwarf varieties of plants are defi- there are projects around the globe to develop cient in the synthesis or sensing of such markers because many varieties of B. rapa the plant hormone gibberellin – a are used as crops. If any of this morphological steroid-like hormone with several variation has a simple genetic basis, there are steps in its pathway of synthesis. obvious educational opportunities in this area. We are likely to find mutations The key educational advantage of using this that abolish many of these steps, plant model is that all stages of the exercises will and complementation testing be “hands on” and the system is amenable to stu- among such mutants illustrates dents designing their own experiments. If any of the concept of using genetics to you have educational interests, we intend to have identify the steps of a biochemi- a website established in a year or so at which you cal pathway. Dwarf plants can can track our progress and request materials.

Scott Woody (left) showing the extensive branching and intermingling of Arabidop- The seven seed packages shown below are a sampling sis flowering stalks compared to the single of the range of B. rapa crops, and the tremendous main stalk of a rapid-cycling B. rapa line. morphological variation within this single species.

Honors & Awards Faculty

Laura Kiessling – Francis P. Garvan- Ann Palmenberg – Elected President of John M. Olin Award, American Chemi- the American Society for Virology, July cal Society, 2007 2007

Judith Kimble – Fellow, American Asso- Ronald Raines – Fellow, Royal Society ciation for the Advancement of Sciences of Chemistry

Academic Staff

Mary Rabaglia – Chancellor's Award for Excellence in Research (Research Sup- port). 2006 Academic Staff Excellence Awards

Postdocs Undergraduate Majors

Paul D. Boyer Excellence Awards Mary Shine Peterson Scholarship Recipients Reece Goiffon Aaron Goldstrohm Molly Lowndes Si Hui Tan Genetic Switches of the Meng Kwang Tan Post-Transcriptional Kind Amanda Herzog

Kimberly Clark Scholarship Recipient Kevin Beier Matthew Allen Biochem 501 Peer Mentoring Scholars Increased-Utility Contrast Agents Sara Heitkamp for Magnetic Resonance Imaging Paul Buske Kathleen Fitzpatrick Kevin Beier

This award acknowledges postdoctoral scholars who are acknowledged by her/his peers and advisors as one who dis- plays clear promise as a research scientist. Most importantly, the award is to be designated in appreciation of the student’s consistent willingness to contribute to the intellectual and technical potential of his/her fellow students and colleagues through the selfless help of others.

Postdoctoral Fellowships Name Lab Fellowship Declan James Martin American Heart Assn Postdoctoral Fellow Pablo Sobrado Fox American Heart Assn Postdoctoral Fellow Tao Wang Craig American Heart Assn Postdoctoral Fellow Peizhen Yang Craig American Heart Assn Postdoctoral Fellow Ngan Lam Kimble Damon Runyon Fellow Leslie Donato Ansari Genomic Sciences Postdoctoral Trainee Jason McCoy Phillips Genomic Sciences Postdoctoral Trainee Joung-Min Jeong Amasino Global Research Laboratory PD Fellow Takashi Higurashi Craig Human Frontier Science PD Fellow Mitsutomo Abe Amasino Naito Foundation Postdoctoral Fellow Matthew J. Allen Raines/Kiessling NIH Postdoctoral Fellowship Dana Byrd Kimble NIH Postdoctoral Fellowship Frank Kotch Raines NRSA Postdoctoral Fellow Bryan Phillips Kimble NRSA Postdoctoral Fellow Brad Pierce Fox NRSA Postdoctoral Fellow

Graduate Student Fellowships University Name Lab Fellowship Alison Albee Wiese CALS Wisconsin Distinguished Fellow Caroline Davis Record CALS Wisconsin Distinguished Fellow Dennis Harris Cox CALS Wisconsin Distinguished Fellow Thomas utkoskiR Raines CALS Wisconsin Distinguished Fellow Harini Sampath Ntambi CALS Wisconsin Distinguished Fellow Bryan Becklund DeLuca R.H. Burris Fellow Jimmy Hernandez Raines Advanced Opportunity Fellow

Departmental Name Lab Fellowship Ed Huttlin Sussman Biochemistry Scholar Mark Meyer Pike Biochemistry Scholar Lucas Bailey Fox Mary Shine Peterson Frederick Porter Palmenberg Mary Shine Peterson & E.W. Hopkins Fellowships Graeme Garvey Rayment Peterson Fellow Anna Fuezery Markley Wharton Fellow

National/International Name Lab Fellowship Clayton Carlson Ansari AHA Predoctoral Fellow Kara Lynch Martin AHA Predoctoral Fellow Melissa Davis Holden NSF Fellow John May Kiessling NSF Fellow Rex Watkins Raines NSF Fellow

Anticipating Rez's Retirement by Professor Marv Wickens A youthful seduction attended Williams College, but was disappointed Two blocks from the Atlantic, on Brooks Road that its science offerings did not emphasize exper- in Woods Hole, two faculty and four children iments. Feeling he had little to lose, he decided to moved noisily each morning in a cape cedar shin- apply to spend a year abroad in Ghana. In fact, he gle house. From the front door, it was just a quick was the only student selected for the newly initi- walk to the Marine Biological Laboratory — a ated education abroad program; only the science lab that had seen classic work in neurobiology, faculty agreed that a student would not miss too developmental biology and evolution. There, for much material by spending a year away. There, in several summers, Paul and Dorothy Reznikoff Africa, Bill saw entirely different perspectives on worked in their lab, and the children came along ways of living, and, on the side, collected reptiles for a summer in Cape Cod, by the sea. as he had hermit crabs. On a warm summer day in 1951, the four At graduation, Bill welcomed the inevitable, children of the house waded along the shore- and entered graduate school at Johns Hopkins. line, meeting the water as it splashed over the He knew he loved biology and genetics, and so in rocks. 10-year old Bill, in a striped t-shirt and classically Reznikovian orderliness, joined a lab shorts, (photo left), kneeled down on the rough that did little of either. Instead, Charlie Thomas, wet stone to get a better look at the hermit crabs, his thesis advisor, focused on the physical proper- starfish and sea urchins. Ten minutes later, the ties of DNA. Bill’s thesis, entitled “Anatomy of boy was on his bike and off to baseball; but the the SP50 bacteriophage DNA molecule,” looked invertebrates and shoreline had set the boy’s path at structure of DNA. Equally importantly, Phil just as surely as if they had written the CV for his Hartman, his co-advisor, became an inspiration: job application. Hartman not only was a gifted geneticist, but That fall, the family went back together to treated people of all ranks with respect, a trait New York for the academic year, as usual. On that resonated, and has stuck with Bill through- Sundays, Bill’s Dad (a Professor of Medicine and out his career. head of Hematology at Cornell Medical School) In like fashion, the other graduate students would often take Bill into the lab. During one and post-docs in the lab were as important in visit, Paul Reznikoff placed two slides on the lab Bill’s career as the science. Among them were sev- bench next to his son. eral close friends who became terrific scientists “Have a look at this one first,” he said. He and colleagues for years to come: John Abelson, slipped the stained blood sampled under the Fred Blattner, and Tom Kelly, for example. This microscope lens, adjusted the focus, and then slid close-knit group reappeared in many guises and his son in on a rolling chair. Young Bill fiddled collaborations later in Rez’ career. For those of with the focus. you now in grad school, there is a lesson here: the “Now have a look at this one.” His Dad person in the next bay may be with you much slipped in a second slide of stained blood. longer than you think. “But this blood looks so different,” Bill said. One person Bill met in his first year at Hop- “There are so many of those things that are not kins was more important than all the others. just round. They are kind of differently shaped Sitting in his first year classroom course in Bio- and don’t look the same inside either.” chemistry, Bill saw an attractive young woman a The two samples, his father explained, few desks away and thought he really should ask were from a normal patient and from one with her out. Four years later, Cathy Armstrong mar- advanced leukemia. This patient had a Philadel- ried Bill Reznikoff. In the years to come, they phia chromosome – a DNA rearrangement that were to both join the faculty in Madison, and had caused all these cells to grow and take over. have three children, Sarah, Joe and Charlie. The sudden realization that biology, disease and genetics were connected hit home instantly. To Madison, lac and hopping genes And with that epiphany, Bill was hooked: Once Bill and Cathy had finished their PhD the combined power of hermit crabs, genes, and work, they moved to Boston, where Bill joined his father were irresistible. Jonathan Beckwith at Harvard. Beckwith was up on all the new developments in molecular biol- To college, to Africa, to Cathy ogy, excited, interested not just in science but in Bill Reznikoff (or Rez, as his friends call him) society, and a terrific mentor. And what was even 10 better – he was a dyed-in-the-wool geneticist. and the starts of transcription and translation. It With Beckwith, Bill arrived at what was to be was all there in black and white. Bill had provided his intellectual home for years to come: molecu- physical reality to abstract genetic concepts. lar genetics. His first major focus was the lactose In the years that followed, Bill continued to (lac) operon. make important contributions to understanding Understanding the basis of gene regulation, how genes are regulated in bacteria. In the course and of lac in particular, was at the heart of Bill’s of using bacterial transposons as tools, he was work when Bill joined the Biochemistry Depart- drawn into studying the regulation of a particu- ment in 1970. Bill published a landmark paper lar transposon, Tn5. How did this element move five years after arriving: the sequence of the regu- in the genome, and why did it do so as rarely as it latory region of the lac operon1. Here, the bio- did? The consummation of this work was the first chemistry of his PhD. thesis comingled with the structure of a transposase/DNA complex, caught genetics of his post-doc. As the work began, no virtually in the act.2 This work, performed in col- regulatory region had ever been seen at high res- laboration with Ivan Rayment provided a model olution. Using genetics, Bill isolated phage car- for the integrase of HIV and other viruses – a rying portions of the lac operon. He then used resurrection of the pivotal Philadelphia Chromo- these phage to prepare templates to make RNA, some blood sample 50 years earlier! And once and in collaboration with John Abelson, deter- again, the two sides of Bill’s scientific personal- mined the seqence of the RNA (and by inference, ity gave reality to genetics: Charlie Thomas, meet DNA) using now-arcane but then groundbreak- Jon Beckwith. ing methods from the Sanger lab. Two people worked two years to determine this 120 base pair In Madison and beyond sequence: 30 base pairs per person per year, or In addition to doing research, Bill has been an 0.1 bp/person/day. extraordinarily committed member of the uni- Theimmediate outcome of their experiments versity community, as mentor, teacher, and Chair was stunningly simple, tangible and beautiful. of the Biochemistry Department from 1986 to The lac regulatory region (image below). 1991. Bill has trained many terrific students and post-docs, among them four who now are pro- fessors on campus (Gasch, Kiley, Lambert, and Yin). Rez’s interest in education has drawn him into teaching several of key courses in the department; into being an outstanding and dedicated advisor to undergraduates; and being a key father I was a graduate student at the time, and I can figure for several of us faculty in our early years testify that it was a revelation. There, on black- in Madison. Most recently, he has helped spawn boards around the country, was a real promoter programs that enable students in Madison to in the flesh – two regulatory elements, one posi- study abroad, much as he had done in Ghana. tive (CAP site) and one negative (the operator), Bill’s commitment to the University has also drawn him into several trans-campus committees, including participation in the University Committee. When asked what was most critical in that undertaking, Bill describes helping to prevent passage of a State Assembly bill that would have banned E. coli from the State of Wisconsin! When you ask Bill what he has valued most about Madison and the department, he points immediately to the supportive environment that the senior faculty (and Hector DeLuca, Julian Davies and Bob Wells, in particular) created, which he feels helped ensure his success; the great colleagues around campus, with whom Bill continues to collaborate; the lack of interdepartmental barriers, which made it easy to organize The Tn5 transposase DNA complex. 11 and sustain active discussion groups, like the old and the hermit crabs, once again near the Woods Molecular Biology Club, or the more recent E. Hole Marine Biological Lab. Bill will join the coli club. He cannot imagine having come up in center in Comparative Molecular Biology and a better environment. Evolution at the MBL, and has just submitted a And when you ask Madison what it values grant to support that work: retirement, indeed! most about Bill, we point not only to his out- Now, his own three children fully grown and standing scientific contributions and intellect, well on their way, along with his past 59 PhD but also to his exceptional humanity, his will to students, post-docs, and undergrads, Rez will be make things better for others, and to the many back on the beach, in the lab, and at home.

students, post-docs and junior faculty, of all ages 1. Dickson, Abelson, Barnes and Reznikoff (1975) Genetic regula- and inclinations, whom he has helped. tion: the lac control region. Science 187, 27. Thisfall, Bill will ostensibly retire, and move 2. Davies, Goryshin, Reznikoff and Rayment (2000) three-dimen- back to Cape Cod, where he and Cathy have sional structure of the Tn5 synaptic complex transposition interme- built a beautiful home not far from the Atlantic diate. Science 289, 77-85.

Rez's lab children as UW-Madison faculty: Paul Lambert Department of Oncology, Audrey Gasch Department of Genetics, Bill Reznikoff Department of Biochemistry, Tricia Kiley Department of Biomolecular Chemistry, Jerry Yin Departments of Genetics and Psychiatry.

The Department Around the World The Biochemistry Department's undergraduate and graduate students, and post-docs, come from all over the country and globe–from 39 states and 44 nations. This diversity invigorates the atmosphere, heightens the energy level, and smells great at lab dinners. It is a testimonial to the intenationalism of science, and is a vital part of the department's identity.

Note: only one pin per country or state, however more then one person may come from there. 12 Student Faculty Liaison Committee (SFLC) by Jackie Fretz and Sheila Semaan, Co-Chairs IPiB SFLC 2006 has brought in a brand new class of gradu- has morphed into the new IPiB SFLC, which is ate students to UW-Madison. In coordination jointly organized by representatives from both with the Biomolecular Chemistry department departments. As usual many of the social activi- we in biochemistry welcomed our first jointly ties that you may remember from your own days recruited class of students into the newly formed in the department have been maintained includ- Integrated Program in Biochemistry (IPiB). This ing the annual welcome picnic, holiday parties, united graduate program is interdepartmental the egg drop competition, and the departmental and provides a wider range of potential faculty art show. We are also glad to incorporate BMC mentors to the new recruits who have chosen traditions into the social scene of the Biochem- Madison for their graduate careers. The forma- istry department including Friday afternoon tion of IPiB has also served as a bridge between socials in the BMC library. Through the coop- the student bodies of the two departments and eration of the students in both departments the with the help of several enthusiastic graduate 2006-2007 academic year is shaping up to be students from both sides a real sense of commu- memorable not only for the new era that IPiB nity and fellowship has been fostered between ushers into the history of the biochemistry the graduate populations of these departments. department at UW-Madison, but also for the In the spirit of this unity between the two welcoming spirit of community and unity that similarly focused programs at UW the biochem- the respective student bodies have extended to istry Student Faculty Liaison Committee (SFLC) each other during this time of transition.

The Department in Uganda Professor James Ntambi continues to lead an extraor- formed a non-profit student dinary and invaluable program for undergraduates, organization called Village taking them to Uganda to both learn about nutrition Health project. The goals of and put what they learn into practice. The experience this project are to support is meaningful to each student involved. Please take health and nutrition projects a moment and visit the program's website: http:// in developing countries, and to www.villagehealthproject.org to learn more about increase awareness about inter- what Dr Ntambi and his students are doing and have national health issues. done in the past and consider helping out. So far, Village Health Proj- BioSand Water Filter The students come to realize that necessities we ect has supported the building take for granted, such as clean drinking water, food of 28 rainwater tanks in Uganda. These tanks are availability, and receiving an education, are daily a simple, effective way of obtaining clean drinking struggles for the majority of Ugandan citizens. water. In January of 2006, the group confirmed Upon returning home, one of the student groups that all samples collected from water tanks were safe for drinking. They are also trying to help solve the water problem by building BioSand Water filters, which are cheaper than tanks and are used at the household level. Water collected from their current sources is poured through the filter and comes out pathogen-free. The students in the program are doing all this because they believe that in order to improve human health, good nutrition practices and clean water go hand in hand. If you would like to make a donation to this program, please send it to: Village Health Project, 239 Red Gym, 716 Langdon Street, Madison,WI 53706.

Water before and after it is processed with the BioSand filter. 13 Biochemistry Degree Listing May 2005-December 2006 Degree Name (Major Professor) Thesis Title

PhD Miller, Russell Identification and characterization of ligand regulated peptides (Attie) that inhibit the 5 amp-activated protein kinase PhD Reiter, Nick Structure and conformational dynamics of U6 RNA and its chaperone Prp24 (Butcher) PhD Sashital, Dipali Structural investigation of U6 and U2 spliceosomal RNAs (Butcher) PhD Staple, David Structural and thermodynamic investigation of the HIV-1 frameshift site RNA (Butcher) PhD Drees, Julia The Novel RecA Regulator Proteins RecX, DinI, RdgC and PsiB (Cox) PhD Eggington, Julie Deinococcus radiodurans single-stranded DNA-binding protein (Cox) PhD Hobbs, Michael On the Biochemistry of the Recombination Mediator Proteins (Cox) RecO, RecR, RecF and RecX PhD Scancella, Jenifer Characterization of the biosynthetic pathway (DeLuca) of the aryl hydrocarbon receptor ligand indole thiazole methyl ester (ITE)

PhD Schwinn, Marie Influence of 1a,25-Dihydroxyvitamin D3 Analogs on Coactivator Recruitment (DeLuca) to the Vitamin D Receptor Transcriptional Complex PhD Schwartz, Phillip On the mechanism by which monocations activate (Frey) adenosylcobalamin-dependent dioldehydrase PhD Lamont, Liana Molecular Regulation of Germ Cell Number and Fate in the Nematode C. elegans (Kimble) PhD Nojiri, Mari Analysis of CAPS Phosphorylation (Martin) PhD Zornetzer, Gregory Modulation of the Structure and Dynamics of Acyl-Acyl Carrier Protein (Markley) by Fatty Acids of Different Lengths PhD Man, Weng Chi Topology of SCD1 and its co-localization with DGAT2 (Ntambi) in the endoplasmic reticulum PhD Han, Byung Woo Structural Biology of Arabidopsis EMBRYONIC FACTOR 1 (FAC1) (Phillips) and Other Enzymes

14 Degree Name (Major Professor) Thesis Title

PhD McCoy, Jason Structure-Function Relationships in Structural Genomics Targets (Phillips)

PhD Kim, Sungtae Gene Regulation by 1,25-dihydroxyvitamin D3, in Osteoblasts (Pike) PhD Zella, Lee Mechanisms regulating ligand-mediated transcriptional activation (Pike) by the vitamin D receptor PhD Dickson, Kimberly Effects of the ribonuclease inhibitor on the biological activity (Raines) of pancreatic-type ribonucleases PhD Fuchs, Stephen Design and Application of a Cell-permeable Cationic Protein (Raines) PhD Lee, Jinhwan (Eugene) Ribonuclease A Homologs: Catalysis and Cytotoxicity (Raines) PhD Smith, Bryan Ribonuclease Activity: Basis and Control (Raines) PhD Mansoorabadi, Steven Characterization of Paramagnetic Intermediates in Enzymatic Reactions (Reed) PhD Adams, Christian Single Molecule Studies of the Tn5 Transposon (Reznikoff) PhD Hook, Brad PUF proteins: RNA binding, protein interactions and RNA regulation (Wickens) PhD Seay, Daniel Marked for Death: mRNAs Targeted and Destroyed by MPT5, (Wickens) a Saccharomyces cerevisiae PUF Protein MS Bates, Barbara Initial Biochemical Characterization of Plant UBX-domain (Bednarek) Containing Protein (PUX) 11 MS Pillard, Sarah Investigating the role of thermodynamic stability in frameshifting efficiency (Butcher) of the HIV-1 frameshift RNA

Correction to last year's newsletter PhD Hinckley, Glenn T Ligand Effect on the Reduction Potential of the [4Fe – 4S]2+/1+ Couple in Ly- (Frey) sine 2, 3-aminomutase

15 From the Covers Aseem Ansari Judith Kimble

Sen1 functions in termination of transcription by RNA Pol II. Stein- In the C. elegans germ line, germ cells proliferate (green nuclei) at one metz et al. map sites of Sen1-dependent termination by comparing Pol end and progress through meiosis and gametogenesis as they move II occupancy across the entire yeast genome in wild-type and sen1 away from the proliferative region. This image shows a germ line mutant strains. The trace on the cover shows wild-type (dark gray) and (nuclei are blue) obtained from a worm that was labeled with bromo- sen1 mutant (lighter gray) Pol II occupancy for a 50 kb segment of deoxyuridine (BrdU, red) and then chased in the absence of BrdU. chromosome 12. The analysis reveals Sen1-dependent termination on From Crittenden et al. pp 3051. many noncoding RNA genes and some short protein-coding genes (cover design by H. Adam Steinberg) Judith Kimble John Markley C. elegans germ cells (nuclei are orange) proliferate in response to Cell-free protein synthesis and NMR spectroscopy of protein signals from the somatic distal tip cell (grey cell at top of image). The products (combined figure from the minireview series by N. distal tip cell is a component of the stem cell niche. From review by E. Dixon et al., pp. 4131–4169). Morrison and Kimble pp 1068.

16 Ivan Ivan Rayment Julie Mitchell

TRP1 interacting PDZ-domain protein GIPC forms oligomers and Actin is the target of a wide range of natural products which stabilize is localized to intracellular vesicles in human melanocytes. the filamentous form of actin (F-actin) or bind to the monomeric state of actin (G-actin). Shown here are the approximate binding sites of the filament-stabilizing natural products amphidinolide H, dolas- tatin 11, and phalloidin on F-actin. Bill Reznikoff and George Phillips, Julie Jr. Mitchell H. Adam Steinberg's rendering of Tn5 transposase-DNA Proteins self-organize into structures that don't always coincide with complexes at non-specific DNA sites; a probable intermendi- observed crystallography or other methods because of their flexibility. ate in transposase finding specific transposon sequences. Mounting evidence suggests that these induced motions play specific and essential roles in protein function. Adenylate kinase, shown above, offers opportunities for the study of dynamics (cover design by H. Adam Steinberg). 17 Membrane Choregraphy in the Martin Lab by Professor Tom Martin Life without membranes would be terribly diffi- this complex process occur so quickly? Which cult. The contents of our cells would diffuse away constituents of the fusion machinery are dedi- and enzymes would never meet their substrates. cated to specific secretory processes and which To avoid the disaster of dilution, barriers to dif- are universal? fusion were established early in the evolution of cellular life. Fortunately, this was relatively easy Understanding choreography once molecules such as phospholipids appeared through biochemistry on the scene; these amphipathic molecules love Membrane fusion is highly choreographed and and hate water at the same time, and spontane- controlled, and relies on at least three different ously assemble into phospholipid bilayers. mechanisms to promote membrane (phospho- The typical animal cell contains 1010 phos- lipid bilayer) fusion. Specific phospholipids are pholipid molecules lined up in parallel register metabolized to make the bilayers more prone in a bilayer arrangement to cover the cell surface. to fuse; soluble proteins are recruited to special The intrinsic physical properties of bilayers pro- membrane sites to prepare these sites for fusion; vide barriers to prevent the escape of required proteins within the membranes help draw them molecules inside the cell, and prevent invasion together. An important conclusion from our by undesired molecules from the outside. Yet work, and that of many others, is that membrane contemporary cells are not simple closed systems; phospholipids, membrane proteins and soluble instead they import and export a wide variety of proteins engage in sequential encounters that are molecules. Transport mechanisms carry mole- choreographed on the spatially restricted stage of cules across the relatively impermeable phospho- the membrane fusion site. lipid bilayer membrane. Our own work began by developing a new biochemical approach to the problem: we broke Little packets sent from inside the cell open and washed secretory cells, and asked Exocytosis exports large molecules out of a cell. whether filling them with calcium would trig- In exocytosis, an intracellular membrane sac (ves- ger vesicle exocytosis. The answer was both yes icle) carrying cargo fuses with the surface mem- and no. On the one hand, adding calcium to the brane to form a pore that allows release of that membranous “ghosts” did trigger some vesicle cargo. In multicellular organisms, one important fusion with the surface membrane and secre- cargo comprises signaling molecules that mediate tion. We now know this is because key proteins communication between cells. Neurotransmit- in the membranes comprise the basic machinery ters mediate signaling between nerve cells (and for vesicle fusion and its triggering by calcium. enable learning and memory) and peptide hor- However, we also found that adding ATP and a mones communicate between groups of tissues number of soluble proteins back to the cellular to coordinate their physiology (such as insulin ghosts markedly improved the calcium-triggered signaling of glucose utilization). The release of vesicle fusion. We now know that ATP and some these signals into the extracellular space – secre- of the soluble proteins catalyzed the modification tion – occurs only when physiology demands. of a phospholipid that is required for fusion. In Demand is conveyed as an increase in intracel- addition, other key soluble proteins were discov- lular calcium, which triggers vesicle fusion with ered that bind to the vesicle and to membrane the surface membrane. This controlled fusion of proteins to help vesicles line up at the membrane vesicles with the membrane is called “regulated to establish a fusion-ready state. exocytosis.” The time required for calcium trig- Our current understanding of the choreog- gering of vesicle fusion varies enormously: for raphy of membrane fusion reveals that it relies example, it occurs within milliseconds in the ner- on many players, as seen in the figure. Firstly, the vous system, and more slowly in the pancreas, as machinery is prepared for fusion when a phos- it releases insulin in response to glucose. phorylated lipid (called PIP2) is synthesized by In the Martin lab, we want to understand ATP-dependent phosphorylation. A protein membrane fusion and its regulation. What is (in black, called CAPS) that recognizes PIP2 is the cellular machinery that allows the mixing of then recruited. CAPS binds to both vesicle and vesicle bilayers with surface membrane bilayers surface membrane (in interactions with PIP2 as to form a pore? How can a rise in intracellular well as the dark grey protein) and helps align the calcium set this process in motion? How does vesicle at fusion sites. When vesicles are prop- 18 erly aligned, membrane proteins (in shades of phospholipid mixing process? What is the exact grey) called SNAREs draw the membranes close alignment of the proteins that choreograph this together. SNAREs are pulled further into close process and in what temporal sequence do they apposition when a calcium-dependent switch (in interact? What is the role of numerous other pro- grey-green, called synaptotagmin) binds to the teins that are known to be required for the overall SNARE proteins when calcium levels rise. This execution of regulated membrane fusion? triggers membrane fusion at a focal site to form a The last decade has revealed aspects of the pore that allows cargo (neurotransmitter or pep- choreography: who moves where and touches who tide hormone) to be released. to cause membranes to fuse only at the right place and time. A new era of synthetic biology now per- What lies ahead mits us to make artificial membranes of defined The progress we and others have made is satisfy- phospholipid composition and utilize purified ing not only for its own sake, but also because it proteins to reassemble the machinery of mem- raises many new questions. How are fusion sites brane fusion and reconstitute its function in the on the plasma membrane established? What driv- test tube (or rather microtitre plate or microscope ing forces overcome the repulsion of membranes slide). On this highly rarified stage, detailed mech- to fuse? How do participating proteins tug on anistic and biophysical studies of the individual membranes to bend them through an orderly players involved in the choreography await.

Some of the players (SNAREs, PIP2, synaptotagmin, CAPS) engaging in sequential interactions that prepare and execute vesicle fusion for neurotransmitter and peptide secretion.

Exploded views of calcium-triggering mechanism for vesicle fusion showing calcium-bound synaptotagmin interacting with plasma membrane and SNARE proteins.

19 Rememering Jack Gorski by Professor Henry A. Lardy "A gentle spirit, warm and unaffected, yet with great strength of character, a penetrating intellect and a fierce desire to learn and understand. Reading Jack’s papers inspired me, as a beginning graduate student, to join the field; getting to know him helped keep me in it". Keith Yamamoto at UCSF

Jack became an Assistant Profes- Phillips Professorship (1985) and the sor of Physiology and Biophysics at Hilldale Award in Biological Science the University of Illinois-Urbana (1991). He was elected to the Ameri- in 1961. There, he and his students can Academy of Arts and Sciences were the first to clarify the function (1986) and the National Academy of estrogens. The steroid bound to of Science (1993). The University of an 8S protein in the cytosol, was Bordeaux added the title “Docteur transported into the nucleus where it Honoris Causa” to his list of honors dissociated to a 5S comlex. No recep- and Current Contents recognized Jack tor protein was found in the nucleus as one of 500 “Most Cited” scientists unless the tissue had been treated in the world. with estrogen. All of the steroid Jack’s talents were expressed also receptor proteins could be removed in his hobby—dairy cattle. He worked The death of Jack Gorski on August from the cytosol by administering on the show circuit while still in high 30, 2006 took a brilliant but modest relatively large doses of estradiol. school. When his profession provided investigator, an effective teacher, and a The elucidation of the mechanism the necessary capital, he bought pure- practical dairyman from this commu- of estrogen function served as a pat- bred cows and placed them with farm- nity. Jack was born in Green Bay, Wis- tern for the function of other hor- ers who received their milk in exchange consin on March 14, 1931. His family mones in many different laboratories. for feed and care. Jack received their moved to Milwaukee and he attended These discoveries and Jack’s contin- calves that had been sired by bulls with school in Wauwatosa. He began col- ued work lead to his being recognized exceptional genetic potential for con- lege at California Polytech but chose as a highly creative and competent formation and milk production. To the University of Wisconsin-Madison investigator. He received the Oppen- increase the value and marketability of to complete a B.S. degree in 1953. heimer Award (1971), the Robert Wil- his cattle, Jack exhibited them at fairs His introduction to hormone research liams Distinguished Leadership Award and Dairy Breed Competitions. His occurred at Washington State Univer- (1987) and the Fred Koch Award wins included the Grand Champion sity, Pullman, where after seven research (1995) from the Endocrine Soci- Jersey Cow at the Wisconsin State papers, he earned his M.S. (1956) and ety; the Mentor Award from Women Fair in 2002. Even this year when his Ph.D. (1958) degrees. It was there that in Endocrinology (2001); the NIH health was a problem, Jack won the Jack and Harriet Fischer were married Merit Award (1986) and was elected Reserve Grand Champion with one of in 1955. Many knew them as tennis President of the Endocrine Society in his cows and placed a younger animal and biking friends. Their daughter, 1990. He was named Distinguished at the head of its class at the Wisconsin JoAnne Gorski Alkire, resides in Min- Graduate (1994) and Distinguished State Jersey Show. neapolis and their son, Michael, lives Alumnus (2001) by Washington State Jack’s greatest legacy came from in Stamford, Connecticut. University. In 1973 Jack moved from his teaching and mentoring. Forty- As a postdoctorate fellow he spent his professorship at Illinois to become five of his students earned Doctorate a year in the renowned steroid labora- a Professor in three departments at degrees and he trained fifty Postdoc- tory at the University of Utah and three this University—Biochemistry, Dairy torate fellows. We remember him as an years with another estrogen pioneer, Science, and Animal Sciences. UW- outstanding scientist with a friendly, Gerry Mueller, at the McArdle labora- Madison presented Jack with the Paul unassuming manner. tory on this campus. With Gerry, Jack explored the earliest effects of estrogen on the induction of nucleotide and "We have all lost a great scientist and a great man, but he protein synthesis in uterine tissue. leaves a strong legacy in science, scholarship, and mentoring, and he still lives in our memories as a true human being". John Katzenellenbogen, University of Illinois Urbana-Champaign 20 In Memorium

Bentley, Orville G Johnson, Ralph M Jr. Rasmussen, Howard (PhD 1947 P. Phillips) (MS 1947, PhD 1948 Strong) (Assoc. Professor 1961-1965) 2006 February 26, 2006 April 22, 2005 Fager, Earl E C Lennon, James Roberts, Anita Bauer (MS 1948 Burris) (Animal Research Tech. 1990-2005) (PhD 1968 DeLuca) 2004 August 11, 2006 May 26, 2006 Feeney, Robert E. MacLeod, Patricia Robinson Stocking, C. Ralph (MS 1940, PhD 1942 Strong) (PhD 1949 Lardy) (Postdoc w/Burris 1956) September 21, 2006 August 17, 2006 May 25, 2006 Garbers, David Olson, Lee Charles Wagner, Marion (PhD 1972 Lardy) (MS 1962 Burris) Technician for Lardy October 2006 2006 December 2006 Gorski, Jack Pressman, Berton (Professor 1973-1997 and (MS 1950, PhD 1953 Lardy) Emeritus Professor 1997-2006) June 2006 August 30, 2006

When is motor not a motor? by Ivan Rayment A Kinesin Motor without a Nucleotide Binding Site

It is widely accepted that kinesin molecular motors contain a motor domain that hydrolyzes ATP and through a series of nucleotide-dependent conformational changes translate the free energy of hydrolysis into directed movement. Thus it comes as a complete surprise that the kinesin related protein Vik1 contains a motor domain, but does not include an active site. This non-motor polypeptide heterodimerizes with the kinesin Kar3. Surprisingly, Vik1 can bind tightly to microtubules indepen- dently of Kar3, but still permits movement of Kar3 along microtubules. These traits demand that there is communication between Kar3 and Vik1, perhaps through a novel strain-dependent mechanism, that allows the binding affinity of Vik1 for microtubules to be modulated by the nucleotide state of Kar3. From an evolutionary viewpoint it is appears that Vik1 evolved from a primordial gene belonging to the same kinesin family as Kar3. Remarkably, the ability to bind and hydrolyze nucleotide was lost during evolution, but the ability to interact with microtubules and communicate with its associated motor protein Kar3 was retained. These studies suggest new variations of molecular motor interactions await discovery. See the March 27th issue of Cell for more details.

2211 NMRFAM Continues to Break New Ground by Professor John Markley The National Magnetic Resonance Facility ers, workstations, and facility staff offices (hence (NMRFAM), located in the Biochemistry Depart- 35.4% the surface area on which the Packers play). ment, is one of the premier centers for biomolec- The facility set a new standard and has been vis- ular NMR spectroscopy in the world. Researchers ited by groups from other institutions designing from all over the world use NMRFAM as a site NMR laboratories, including Pacific Northwest for data collection, advice, and training. In addi- Laboratories, the New York Structural Genomics tion, NMRFAM carries out research in technol- Center, MIT, and the University of Utah. Sam ogy development and novel applications of bio- Butcher joined the Biochemistry faculty in Sep- molecular NMR. tember, 2000, and became a co-PI on the grants Beginings that support NMRFAM. Local and External Advi- sory Committees review NMRFAM’s progress and NMRFAM has a long history. John Markley provide useful guidance. established NMRFAM in 1985, modeling it NMRFAM currently houses nine NMR spec- after a facility he ran at Purdue. Initial funding trometers: one 900 MHz, one 800 MHz, one 750 came from the University of Wisconsin‑Madison, MHz, three 600 MHz, two 500 MHz, and one National Institutes of Health, National Science 400 MHz. All but one 500 and the 400 MHz Foundation, and U.S. Department of Agricul- machine are equipped with state-of-the-art cryo- ture. The facility opened in the 1985 Wing of genic probes, which enable nearly 10-fold faster Biochemistry with new spectrometers operating data collection. Instrumentation funding has at 400 and 500 MHz. NMRFAM outgrew this come from the NIH and NSF with gen- site with the addition of its sixth spectrometer, erous matching from UW‑Madison. a 750 MHz NMR instrument that had to be All of the magnets in NMRFAM housed temporarily off site. are of the superconducting vari- A new facility: ety and must be cooled by liquid 9 magnets, 1/3 of Lambeau field helium. Very recently, NMRFAM The NMRFAM staff members got to design a installed a helium recycling system world-class NMR laboratory as part of the Bio- that captures boil-off helium (a non- chemistry Addition completed in 1998. Ed Moo- renewable resource) in a huge bag. berry, who retired from UW-Madison in March, When the bag fills, the helium is com- 2006, was the major architect of the space and pressed and sent through a pipe under infrastructure. The new space has a hatch in the University Avenue to Engineering Hall, ceiling for delivery of large equipment. It has where it is liquefied and sent back to liquid nitrogen piped in through dewared lines NMRFAM in liquid form. The facil- for magnet fills. The temperature in the magnet ity has excellent computational facilities rooms is controlled to within ±0.5 °C. The facil- for NMR data processing and quantum chemical ity has 18,000 ft2 for NMR spectrometers and calculations. their support plus 2,400 ft2 for computer serv- Cutting edge NMR Under the able direction of William Milo Wes- tler and other members of its scientific staff, NMRFAM continues to expand the frontiers of biomolecular NMR spectroscopy through resource technology development programs in the important areas of: (1) fast data collection and automated data analysis, (2) technology for larger proteins and complexes, (3) investigations of metal-containing (paramagnetic) proteins, (4) dynamics of macromolecules, (5) structure-function investigation of RNA molecules and their complexes with metal ions and proteins, and (6) the detection and quantification of small molecule metabolites in cell extracts. A major goal at NMRFAM is to make these investigations faster and less costly. NMRFAM 22 offers start-to-finish support for biomedical NMR and the secondary structure. NMRFAM makes investigations and is prepared to lend support, as this capability, known as “PINE”, available to the needed, in one or more of the following: (1) strat- community from a webserver on its website. The egy evaluation, (2) sample preparation, (3) feasibil- output of PINE can be viewed for quality control ity studies, (4) data collection, and (5) data analysis by standard software packages used for manual and structure determination. Our aim is to facili- assignments that display strips from experimental tate the efficient pursuit of new knowledge by pro- data. PINE takes minutes to perform operations viding researchers with resources matched to their that take days by hand. particular needs. NMRFAM provides young investigators and experienced spectroscopists access to In the last year state-of-the-art instrumentation with support for The 2005-2006 NMRFAM annual report lists multiple modes of data collection. Protocols, pulse >100 publications supported by NMRFAM. sequences, and software tools developed through Some of these are by independent users of the NMRFAM’s research activities are made available facility, but many represent collaborations with to the general scientific community. The aim is to researchers on or off campus. NMRFAM is develop and disseminate advanced approaches to always looking for challenging collaborative proj- experiment design and data analysis that cover all ects that can make use of its technology and serve steps in a biomolecular NMR investigation, from to drive it in new directions. Examples of recently cloning through data deposition. NMRFAM completed collaborative projects that involved hosts distinguished visiting scientists and NMRFAM include: the structure of essential pre- presents workshops attended by scientists mRNA processing factor Prp24 (Sam Butcher, from all over the world. George Phillips, and David Brow); the solution The Center for Eukaryotic Structural structure of YggX, a prokaryotic protein involved Genomics (CESG) uses NMRFAM as its in Fe(II) trafficking (with Diana Downs, UW Bac- primary site for data collection and analy- teriology); “solution structure of the N-domain sis for protein structure determinations of Wilson disease protein showing its unique and collaborates with NMRFAM nucleotide-binding environment and effects of staff members on the development disease mutations (with Oleg Dmitriev, Univ. of of improved technology. This col- Saskatchewan, and Svetlana Lutsenko, Oregon laboration led to the first implemen- Health & Science Univ.); NMR titration study of tation of a new strategy for data col- the Rieske protein from Thermus thermophilus lection in which the spectral space of a par- demonstrating the role of iron-ligated histidines ticular three-dimensional NMR experiment is in the pH dependence of the reduction potential sampled iteratively by collecting two-dimensional (with James Fee, Scripps); solution structures of tilted planes with on-the-fly peak recognition of spinach acyl carrier protein with decanoate and each plane and calculation of the most optimal stearate (with Brian Fox); solution structure of next plane to collect. If the algorithm predicts that CalC providing structural insight into the self- the additional information from the plane will sacrifice mechanism of enediyne resistance (with improve the model of peak locations, the plane is Jon Thorson, UW Pharmacy School); micelle- collected; if not, the experiment is complete, and induced folding of a spinach thylakoid soluble the system moves on to the next experiment. This phosphoprotein and its functional implications strategy, called “HIFI-NMR” (High Resolution (with Inger Carlberg, Stockholm Univ. Sweden, Iterative Frequency Identification for NMR), as and Alexander Vener, Linköping Univ., Sweden); currently implemented speeds up data collec- solution structure of a small protein containing tion by an order of magnitude. The approach has a fluorinated side chain in its core (with Prof. enormous potential in that it is easily interfaced Sam Gellman, UW Chemistry); NMR charac- with automated assignment of signals and other terizations of an amyloidogenic conformational steps in solution structure determination. ensemble of the PI3K SH3 domain (with Eugene Another collaboration with CESG has led to Derose, Cindy Putnam-Evans, and Kwang Hun a complementary set of tools that take as input Lim, East Carolina Univ. and Robert London, peak lists associated with particular NMR experi- NIEHS, Research Triangle NC). ments (the output from HIFI-NMR or other data For more information, please contact Anne collection strategies) and the protein sequence Lynn Gillian-Daniel (608-262-3173) or consult and provides as output assigned chemical shifts the NMRFAM website: www.nmrfam.wisc.edu 23 Department of Biochemistry Alumnus – Natalie DeWitt by Mike Sussman Senior Editor Nature Developmental Biology From Wisconsin Natalie DeWitt arrived in the Sussman lab Sussman received his polishing (?), in the fresh from a BS in Biochemistry at Univer- yeast plasma membrane genetics laboratory sity of Maryland during a rotation in the of Carolyn Slayman at the Yale School of fall of 1987, and graduated with a PhD Medicine. Her decision to settle in at Yale from the CMB Program in 1994. She pub- as a postdoctoral associate with Carolyn, was lished three papers from her thesis, in the preceded by interesting and brief detours respected journals Genetics, Plant Physiology caused by her first postdoctoral mentor at and Plant Cell. Her major accomplishment a Southern university not receiving tenure, in that body of work was the demonstration and another brief sojourn to England to that one of the 11 genes encoding the Ara- taste European culture. After finishing up at bidopsis thaliana plasma membrane proton Yale in 1999, she proceeded on to her first pump (H+-ATPase) family is specifically real job, as a research editor at the then ‘new’ and highly expressed in companion cells of journal, Nature Biotechnology. In 2001 the phloem. For those of you who work with she was promoted to Senior Editor for the animals, rather than our green friends, the mother-ship journal Nature, and was also plants, be aware that the proton pump per- the founding editor for their San Francisco forms the same essential function in plants office. as the sodium pump in animals. In addition, the phloem is sort of like the veins and To Editor at Nature blood since it is the tissue through which all Over the past four years as Nature’s editor in of the sugar made in leaves moves to hetero- charge of developmental biology, Natalie has Mike Sussman (lower left). trophic growing or storage tissues such as been responsible for scientific manuscripts Jeff Harper (upper left) postdoc then, fruits and roots. Her work was one of the on stem cells, embryology, cloning and now professor at University of Nevada at Reno. first in plants to use epitope tags to identify angiogenesis, including some of the most Eric Schaller (center) also CMB student the location of any protein, at both the light highly cited papers in all of biology. She has then, now professor at Dartmouth Uni- versity. and electron microscopy level. Furthermore, authored many editorials, news stories, press Lorelei Manney (center), technician then, one of her modified genes turned out to be releases and scientific highlights for Nature now mom living somewhere in Texas. a dominant positive transgene that created and other Nature Publishing group journals. Natalie DeWitt (right). ‘acid resistant’ plants. She was also involved She has organized Nature-sponsored scien- in the early stages of the reverse genetic gene tific conferences and press conferences and knockout technology that Sussman’s lab serves on the editorial board of the Interna- developed (with large-scale gardening help tional Society for Stem Cell Research and from colleague Rick Amasino) and provided on the board of directors for the Northern to the international research community, California branch of the National Asso- from 1996-2001. Natalie’s research accom- ciation of Scientific Writers Association. All plishments helped Sussman get tenure (some of this arose after, and perhaps in spite of, people may say this is a blemish, rather than her humble beginnings as an Arabidopsis a plus). researcher and graduate student in the Suss- man lab working with the ‘original’ (green) Through a Transition stem cells! Whether in the lab, or at the key- After escaping Wisconsin, she performed board, her work has always been typified as her postdoctoral work in the same lab where being innovative, careful, and timely. From the Labs This has been a productive and exciting year in network models that describe pathways that are our laboratory. We are engaged in research aimed disregulated in diabetes. at identifying genes involved in diabetes suscepti- We have been joined by several new people bility. This past year, we published our first posi- this year. Jeremy Lavine, an MD/PhD student is tional cloning success, the identification ofSorCS1 working with Phil Raess on b-cell proliferation as a diabetes susceptibility gene responsible for a mechanisms. Bill Olver, a biochemistry PhD stu- quantitative trait locus we originally mapped when dent, is working on our genetics projects. Chris- Jonathan Stoehr was in the lab several years ago. tine Ferara, an MD/PhD student with Chris Alan Attie Much of the credit for this milestone goes to Susie Newgard at Duke University, is spending a few Lab Clee, who was quite resilient in pursuing a very years in our lab working on several joint projects tough project. Susie just was awarded a Scientist between our lab and the Newgard lab. Dawn Belt Development Grant from the American Heart Davis is an MD/PhD post-doc who just com- Association. She has recently been on many job pleted her Endocrinology fellowship at UW Hos- interviews and will likely be happily situated in pital and is working with us on our gene discovery an independent tenure-track position somewhere projects. Enpeng Zhao is also deeply involved in else later this year. Our collaborators in San Anto- many of our projects. He is also eagerly awaiting nio and Los Angeles have discovered that single the arrival of his first child, due this spring.Angie nucleotide polymorphisms in SorCS1 are associ- Tebon Oler and Kathy Schueler still travel all the ated with diabetes in Mexican-Americans. Others corners of the world and have time to do wonder- are now investigating the involvement of this gene ful work in the laboratory. Dan Blasiole is bravely in diabetes in other human populations. upholding a presence for the lab in the lipid field Summer Raines and Oliver Richards are despite our much higher profile in recent years studying SorCS1 function. SorCS1 binds to in the diabetes field. Mark Keller has a hand in PDGF, a critical regulator of pericyte recruitment virtually every project in the lab and has helped to blood vessels. So, they’re exploring the hypoth- us move into several new and exciting areas. He esis that SorCS1 plays a role in angiogenesis in the is about to embark on a drug discovery project islet vasculature. to follow up on some exciting leads we have with This past year, Mary Rabaglia was awarded compounds that stimulate insulin secretion. Jes- the Academic Staff Award at a ceremony in the sica Byers Flowers graduated last summer and is Chancellor’s Mansion. The award recognizes her now doing a clinical nutrition internship at UW many decades of dedicated work at the university Hospital. She really enjoys the clinical work and and just how really fantastic she is. envisions combining basic research and clinical We are also collecting highly informative nutrition in her future career. data that links gene expression in various tis- Alan is thrilled by everything and everyone in sues, including pancreatic islets, with diabetes the lab. We are involved in many areas we could traits and with markers in the genome. With not have predicted before. The lab has developed our wonderful statistician collaborators, Chris- a lot of new infrastructure, which is extending tina Kendziorski and Brian Yandell (and their our capabilities and our level of sophistication in wonderful graduate students), we’re developing genetics and genomics research.

This past year was an eventful one for the the ribosome. Dipa and Nick’s research projects Butcher lab. It is a story of eight fantastic gradu- are at such exciting stages right now that they ate students at different stages in their careers. have both decided to stay for a little while longer Congratulations to David Staple, Dipa Sashital in the lab as postdocs while they wrap things and Nick Reiter for successfully defending their up. This is great news for the lab, but it is just a Ph.D. theses. They were my first graduate stu- matter of months before they go off to start their dents to join the lab (in 2001), and all three have “real” postdocs. In light of the turnover this year, done remarkably well. David is now a postdoc at it was the perfect time to recruit some new grad- Sam Butcher the University of California at Santa Cruz in the uate students. We were fortunate to have Ashley Lab laboratory of Harry Noller, where he is studying Richie and Steve Martin-Tumasz, 2 very bright 25 first year graduate students, join the lab this year. fourth year as a graduate student and will likely Additionally, we had Vincenzo Venditti as a vis- be defending his Ph.D. thesis in the upcoming iting graduate student on loan from the Univer- year, and Ryan Marcheschi is finishing his third sity of Siena, Italy. Jared Davis is finishing his year and is busy solving his first RNA structure.

Jeremy van Vleet (5th year graduate student) wife had a baby girl, Sophia, in April. Lac Lee has been spending an unprecedented number who graduated here in 1999 also works there. of hours in the lab since his wife Jennifer, of 8 Professor Al Hengge (Utah State University, months, left for Denmark on a Fulbright Fellow- Logan), past scientist in this lab, is here at UW- ship. Jennifer is working for Lisbeth Olsson at Madison for this fall on sabbatical. He has been the Center for Microbial Biotechnology at Tech- working with John Denu in the Biomolecular nical University of Denmark. Chemistry department. Laurie Reinhardt (Assoc. scientist) has John Marlier (Professor at Cal Poly in Cali- Mo Cleland made gamma-amino ATP and ethyl-CoA for fornia) was here this summer working on the N- Lab use in X-ray studies in Ivan Rayment's lab and 15 isotope effects on semicarbazide hydrolysis by is determining isotope effects on ornithine trans- urea. His work on urea catalyzed hydrolysis of for- carbamoylase. Mark Anderson (Asst. scientist) mamide was published this year in Biochemistry. has been determining N-15 isotope effects on Jill Rawlings (Professor at Auburn Uni- ethanolamine ammonia lyase and tryptophan versity-Montgomery in Alabama) was here this monooxygenase. He is also analyzing the N-15 summer finishing up work on metal catalyzed content of leaf cutter ants and the food they eat hydrolysis of phosphodiesters, with a paper in in a collaborative study of nitrogen fixation in press in JACS from this work. these insects. Mo went to the Isotopes Gordon Confer- We have three undergraduates (Brian Wrat- ence in California in February, but otherwise his ney, Greg Peters, and Fiona Chu) working in out of town trips have been to visit his daugh- the lab this fall. ters or see operas (the Sarasota Opera in Florida Yong Liu who graduated here in December in March and the Wagner ring cycle operas in with her master’s degree now has a full time job Orange County in October). He and Paul Cook with Genentech in San Francisco. Kirk Wright have written a book on Enzyme Kinetics which who finished his postdoc here in 2003 recently should be published in the spring and he is cor- changed jobs to Novartis in Boston. He and his recting page proof as this is written.

Current Lab News: ing his possible run in with a bot fly!). Rachel Britt passed her prelim exam in April There’s no end to the excitement we get into in 2006. Congratulations Rachel! the Cox lab! Julia Cox plans to defend her thesis this coming February. She is the last of our Julie/ Awards: Julias, with no more in sight for a while. She’s Dennis Harris received a Sullivan Wiscon- got a job offer and will begin work as a patent sin Distinguished Graduate Fellowship. engineer. She’ll prosecute patents with a law firm Reece Goiffon received a 2006-2007 Wis- Mike Cox as soon as she gets her Ph.D. consin Hilldale Undergraduate Research Award. Lab Vessela Petrova took some time off this past Meng Kwang Marcus Tan received a summer to travel from western Russia all the 2006-2007 Wisconsin Hilldale Undergraduate way across Asia to Beijing, stopping in Mongolia Research Award. where she lived in a yurt (Mongolians call them Comings: ger) for several days. The pictures she showed us Postdoc Akiko Sakasai joined the lab this of her trip were amazing. past summer after training with Akira Shinohara Reece Goiffon traveled to Ecuador this past in Japan. Graduate students Marielle Gruenic summer and entertained us all with his blog that and Audrey Klingele joined the lab after fall kept us up to date on all his adventures (includ- rotations. Welcome, Akiko, Marielle, and Audrey. 26 Southwest very nicely. We’re giving her a few more months before we start dropping in for visits to escape this cold Wisconsin winter weather. We miss you all very much. Good luck in your new digs.

Past Lab News: Li-Chun Huang wrote to say that she’s joined Cell Genesys’ Assay Development group for a nine-month assignment of a pre-validation project. Weddings and Babies: No weddings this past year, but we do have babies to report: Goings: Alberto Roca and Nancy Aguilar sent us Julia Drees, Julie Eggington and Michael news that they became parents on September 21, Hobbs all defended their theses this past year. 2006. Andrea Isabel weighed 6 lbs 12 oz and was What a party! 20 inches long. I looked at her website and can Julia Drees is now a postdoc at The Univer- say that she is one very pretty baby girl. Con- sity of California, San Francisco in the Alan Wu gratulations to you both on your new baby. lab. She did find time to travel to Yosemite and Mike Cox attended a few meetings this past Alaska before really getting down to work as a year that included a trip to the ASBMB Annual postdoc. Meeting in San Francisco in April. He and Beth Julie Eggington is now a postdoc at the took a side trip in this little red car. Mike seems University of Utah, Salt Lake City in the Brenda to have enjoyed himself. Bass lab. She wrote to say that she got a chance to visit Australia and her Grandma before beginning work in the lab. Michael Hobbs is now a scientist at Invitro- gen here in Madison. Shelley Lusetti left us in August and is now an Assistant Professor at New Mexico State Uni- versity, Las Cruces. She’s contacted us to say that she and her family have settled into life in the

27 Greetings from the Craig Lab. alumni have such fond memories of Madison! Since the last Craig Lab installment of the Patrick D’Silva has returned home to take a Newsletter, much has happened. The lab has position as Assistant Professor of Biochemistry at successfully survived the past year with Betty as the Indian Institute of Science at Bangalore. He Chair of the Department, making steady progress will continue his work on mitochondrial import, uncovering the mysteries of molecular chaperone focusing on the mammalian import motor. Good action. Here is the NEWS! luck Patrick (and Savita and Serena) in your new Peggy Huang has left her “ribosome-associ- position! We are awaiting Patrick’s first report of Betty Craig ated chaperone” life and moved on to her postdoc- life as a professor. During the past year Thomas Lab toral position in the lab of Arlen Johnson at the Lee has joined Brenda Schilke, Willy Walter, University of Texas – Austin, where she is study- Dirk Schiller, and Masaya Hayashi in the “mito ing ribosome biogenesis. As luck would have it, import” group. Thomas came from the Univer- Peggy’s move dovetailed with the work of Alison sity of Colorado, where he studied the regula- Meyer, one of Peggy’s successors on the “ribosome/ tion of MAP kinase using Hydrogen and mass chaperone” project. Alison made the unexpected spectrometry in Natalie Ahn’s lab. He has taken finding that the “other” ribosome-associated J- on the challenge of understanding the dynam- protein, Jjj1, works in ribosome subunit biogen- ics of the Tim44:Ssc1 interaction and becoming esis. A productive collaboration between the Craig immersed in yeast genetics. and Johnson labs is now underway. Our focus on the complexity of the cytosol During the past year Peizhen Yang joined continues. But by the time you read this, Rebecca Alison and Samantha Herbst on the ribosome- Aron will have defended her thesis and moved to centric project. Peizhen moved across Henry San Francisco to join Paul Muchowski’s lab. After Mall from Genetics, where she did her PhD in concentrating on how Sis1 works to maintain Rick Vierstra’s lab working on the proteasome. In the yeast prion [RNQ+], she will delve into the addition, Jeanette Waltner a CMB grad student, world of protein aggregation and neurological has joined the lab and is following up the work of disease model systems in mammalian cells. The Helene Eisenman, trying to figure out how Zuo chaperone:prion project will continue in the able and Ssz, the “weird” Hsp70, are involved in turn- hands of Takashi Higurashi, while Chandan ing on pleiotropic drug resistance. Sahi has taken on the challenge of understanding Pascual Lopez has come and gone for his the complexities of the multiple J-proteins that sabbatical year. This was Pascual’s third (fourth?) populate the cytosol. visit to the lab, first as a young bachelor postdoc, As has become the norm Jarek Marsalek now on sabbatical from his position as Associ- joined us as a visiting professor from the Univer- ate Professor at the University of Zaragoza and sity of Gdansk for three months this fall, provid- father of four. Antonio Pascual Lopez Peña, born ing an infusion of energy into our Fe-S cluster on November 7th, is arguably the most visible and Yfh1 activities, working with Brenda, Amy product of his recent visit to Madison (although Andrew and Tao Wang. Amy’s work has been we are still working on that paper on stimulation going well and she will shortly receive the “Lame of Hsp70 ATPase activity!). Duck” from Rebecca. For the alumni of the Qinglian Liu, a Craig Lab grad from 2002, Lab, it will be reassuring for you to know that gave birth last summer to a daughter that she the “Lame Duck”, the oldest member of the lab and her husband named Monona Jiayi. Pascual (with the exception of Betty) who becomes the in jest protested – saying he owned that name, as responsibility of the eldest grad student, is doing he and Maria had named one of their daughter’s well, although that Ace bandage around his leg is Monona several years ago. It is nice to see that lab becoming a little tattered.

28 News from the Vitamin D DeLuca Lab: amas who is studying the use of vitamin D ana- Yesterday I was in the Information Technol- logs for the treatment of prostate cancer. During ogy Media Center getting their help on some of the past year, I have had two graduate students our needs and I was reminded by Laura Vander- who have completed their work, namely Marie ploeg that it has been two years since I’ve written Schwinn and Jeni Scancella. Marie completed a laboratory communication to my former asso- her work on the binding of coactivators as influ- ciates. Although I have always taken the position enced by ligand modification and Jeni com- that probably former alumni don’t really want to pleted her studies on the biosynthesis of the Hector DeLuca read newsletters, I decided that you don’t have precursor for the AhR ligand. In addition, I have Lab to read it but I would convey what the picture is had two graduating students who are enrolled in currently in my laboratory. the medical program here on campus, namely Most important is that I am still active and Katie Williams and Ehren Rudolph. Katie has I’m enjoying the things that we are currently completed her Ph.D., whereas Ehren still has to doing. Fortunately, unlike many of you, I am write his Ph.D. thesis but will be completing it not faced with deadlines and requirements of some time during the year. I will not be taking grant applications. It is precisely now that I am on any additional graduate students but will be able to do only those things that I care to do. As accepting postdoctorates since the commitment a result, I am really enjoying myself in my cur- to them is a much more shorter term than a rent research setting without the responsibilities graduate student. of being the Chair of Biochemistry and without I am both sorry and happy to report that the responsibilities of having to apply for research Claudia Zierold has decided to develop her career grants. Although my laboratory is somewhat further and has left my laboratory and has taken smaller than it used to be, I still have approxi- on an Associate Scientist position in the Dept. of mately 25 people working in my group. This is Pathology & Lab Medicine in the Medical School. exclusive of Pat Mings who continues to keep She appears extremely happy with her new posi- me “on track” with all of my University office tion and is working very hard. Other postdocs work and Wendy Hellwig who does a great job who have left the laboratory are Shirin Akhter of keeping the laboratory supplied and doing all who carried out a very nice piece of work on dem- of the paperwork needed to keep a lab operating. onstrating that calbindin D9k is not required for These two individuals make my life very easy. vitamin D to increase intestinal calcium transport Lori Plum is Director of Research and Develop- and Moises Rivera moved to Boston following his ment for Deltanoid Pharmaceuticals and also is work here in the area of asthma. Two technicians a senior investigator for the vitamin D labora- left the laboratory, Aaron Hirsch and Eric Dan- tory. Other senior investigators include Wendy ielson. Eric has gone on to medical school and Bedale who has worked on inflammatory bowel Aaron has taken a different position in the Madi- disease and is currently working on the osteopo- son area. We had added four technicians in the rosis project, Julia Zella who works on a variety last year: Jennifer Vaughan, Flora Sundersingh, of projects including all aspects of renal failure Laura Jacobson and Shinobu Miyazaki. They patients and the use of vitamin D compounds as have all been excellent additions and I am very well as phosphate binders, and Galina Gutuzova pleased with how hard they work. Of course, we who works on microarray analysis of the actions have the reliable technical skills of Jean Prahl who of vitamin D. Jason Song is just completing his is the jack-of-all-trades and on whom I depend work on the AhR ligand and will be leaving the heavily for many technical aspects of research laboratory to start his own company. As you may that we do. Xiaohong Ma was a marvelous find well know, Janeen Vanhooke has left Madison because of her M.D. background that has made for an Assistant Professorship at Chapel Hill in her a key person for the study of biological activity North Carolina and thus our laboratory has lost in animals. Ellen Lake is our expert on analytical its crystallography capability. aspects of vitamin D and is an important support There are three graduate students remaining for our drug development team. We also are fortu- in my group. Bryan Becklund who is doing an nate to have Jamie Nehring (Mings) who received excellent job in the study of experimental auto- her MS degree from the biotechnology program immune encephalomyelitis, the mouse model of on campus and is now working on colorectal multiple sclerosis; James Kim who is working cancer and on the mouse model of diabetes. on the effect of vitamin D compounds in the We have had a lot of activity in the chemis- disease Lupus Erythematosus; and Gina Gial- try portion of my research group. We have the 29 ongoing and continuing work of Pawel Grywacz. Development; Linda Leikness, Chief Operations We are fortunate to have Grazia Chiellini who Officer; and Karrie Dresen, an accounting/ also holds a position at the University of Pisa, but administrative assistant to Linda. We also have spends a good share of the year doing chemical a large number of excellent undergraduates who synthesis in my research group. We have a won- work with scientists and graduate students in the derful husband and wife team with Rafal Barycki laboratory. and Katarzyna Barycka. Of course, Rafal Sicin- Margaret and I were really so surprised and ski continues to work with us whenever he can pleased when Tatsuo and Umiko Suda visited us since he has a very high administrative post at the at the end of May in 2005 to be sure that I was University of Warsaw. He has sent us two great physically okay because of my bout with lym- graduate students to work on their Ph.D. jointly phoma. Tatsuo and Umiko had sent us origami between Rafal and our research group: Agnieszka chains to support the fight against lymphoma. Glebocka has received her Ph.D. and will now Tatsuo has been very concerned about my health. come here as a postdoctoral fellow. Katarzyna He has also had some health issues himself but Plonska is still working on her Ph.D. but she is doing extremely well. We were very pleased to spends her summers here in my lab and her win- see them here and we hope we can see them again ters in Poland working on vitamin D synthesis. soon. Padmaja Tadi, a postdoctorate from Hyberadad; I am sorry to announce to those of you who Yun Luo, a Ph.D. from our U.W. Chemistry haven’t heard that Anita Roberts, one of my very Department; and Agnieszka Szczepanska from best students, finally succumbed in her battle Warsaw are all carrying out excellent work in our against gastric cancer. Although given only a chemistry group. couple of months to live, she battled the disease Besides my research group, I have an added for a period of three years and was an inspiration advantage of being part of a company (Deltanoid to all of us. Anita was one of the most marvel- Pharmaceuticals, Inc. located at the Research ous human beings I have ever had the pleasure of Park) that develops raw university inventions to knowing and I know all of you who knew her feel a point where they can be sublicensed to large the same. pharmaceutical companies. In this company, I love to hear from all of you. Please do not Margaret Clagett-Dame is Senior Vice President hesitate to send any kind of communication you and Chief Scientific Officer while I serve as Presi- can. Although you may not hear from me, I want dent and CEO. We have in the group at Research you to know that I appreciate hearing from any Park: Paul Radspinner, Vice President of Business and all of you.

The Frey lab is in transition. Since the last News- shahi and Dawei Chen continue as Scientists in letter report, Glen Hinckley and Phil Schwartz our research program. completed their Ph. D. requirements and received We have welcomed additions to the families their degrees. Glen is a postdoctoral researcher of lab members and recent alumni in Madison. in the College of Engineering, and Phil will do Glen and Michelle Hinckley are proud parents to his postdoctoral work with Vern Schramm at Everett Ariosto Hinckley. Adrian Hegeman and the Albert Einstein College of Medicine. Post- Ericka welcomed their daughter Sylvia Sanders doctoral associates Kaisheng Huang and Elham Hegeman. Alejandro and Paola Yevenes recently Perry Frey Behshad have moved on to permanent positions celebrated the birth of their second daughter, Lab at Amgen and Incyte, respectively. One of our lab Daniela, and their first daughter Belen is very anchors, Frank Ruzicka formally retired, but he excited about her new sister. The Yevenes family continues part-time as a Senior Scientist Emeri- is very happy in Madison. tus. Susan Yang is continuing as a postdoctoral The new book on “Enzymatic Reaction Mecha- associate, and is job hunting this year. Alejandro nisms”, on which Perry and Adrian have been Yevenes has joined the lab as a postdoctoral asso- working for some years, in their spare time, is ciate and is working on phosphoketolase. Alejan- being published by the Oxford University Press dro received his Ph. D. degree in the laboratory and will be out in January of 2007. Adrian and of our long-time friend and associate Emilio Perry feel a sense of accomplishment, as well as Cardemil at the University of Santiago. Ab Arab- relief that it is finally in print. 30 This will be the last year of research in the Frey the lab, and he has thoroughly enjoyed all of his lab. Perry has been planning for the past five years interpersonal interactions with students, post- to retire after 2007. Perry did not submit applica- doctoral associates, and scientists in the Frey lab tions for renewal of the grants that have supported and in other labs of the Department of Biochem- research in the lab for the past 37 years because istry and those of his collaborators. The research of his plans for retirement. In preparation for a completed by the students and other researchers soft landing, recruitment of graduate students in the lab has given Perry great satisfaction and was halted after Phil Schwartz entered the group, pleasure, and he wishes all of his former associ- so Phil is the last graduate student to receive his ates every success and pleasure with their future Ph.D. in the Frey lab. Alejandro Yevenes will be careers. Perry has also been honored to work with the last postdoctoral associate in the group and colleagues in Biochemistry on many collaborative will leave sometime in 2007. Through attrition, research projects, all of which have enriched his the size of the group has been contracted so that professional life. In retirement, Perry will pursue during 2007 all of the lab members will leave interests that he has had to defer because of the for other opportunities. Retirement for Perry is demands of his career in biochemical research. planned for the end of the year. However, he will keep a hand in Biochemistry Perry has felt honored each time a graduate and continue with a few activities in professional student or postdoctoral associate chose to enter organizations.

Exciting times have come to the Kiessling lab over Rachael Carpenter and Adam Courtney. This the past year. The "star" headline goes to Matt west-side team (only half the size of the Stem Allen (who also works in the Raines lab) for win- Cell Lounge) has a large fan following, making ning an NIH K99/R00 Award – one of 58! – to it a force to reckon with in the group. make a successful transition from mentored post- Adam continues to perfect the art of western doc to junior faculty member. This means, how- blotting, and play hockey for the biochemistry ever, that Matt will be here less than a year now. team, following his Canadian upbringing. The Stem Cell Lounge became an official Rachael remains the strong female voice Laura Kiessling entity of the lab, located on the east side. Within needed to keep the male-dominated lab in bal- Lab this lounge, we find Joe Klim, Ratmir Derda, ance, and the unofficial morning coffee maker. Lingyin Li, and April Weir. She hopes to begin agility training this summer Joe Klim passed his preliminary examination with her standard schnauzer, Bryn. over the summer. Joe also adopted hobbies of New PhD holder Erik Puffer enjoys long rowing and playing drums in a concert band. walks on the beach, quiet evenings at home, and Ratmir attended the Gordon Conference deep philosophical conversations regarding the located in beautiful Switzerland and brought meaning of life. back chocolate snacks for everyone. When not Not to be left out, Team Galf insists that they performing ingenious experiments, Ratmir likes were the original “team” of the group. Team Galf to D.J. and represents the Stem Cell Lounge at includes John May and Todd Gruber, two grad the Cardinal. students possessing the uncanny ability to talk Lingyin, a fourth year chemistry gradu- longer at sub-group meetings than everyone else ate student, traveled to China over the summer combined! Emily Dykhuizen, Becca Splain, and affectionately brought back many gifts for and new post-doc Raja Annamalai round out the group. She also revealed her secret talent of the team. being an exceptional pianist, and throws a great Todd has returned to the Kiessling lab after barbeque. his spring internship in San Diego. He walked April has made it to her second year of gradu- out of all of our lives and thought he could ate school alive, despite the threat of tetanus from march right back as if nothing had happened. an accident regarding the Christmas ornament. Team “everybody else” includes Eric Under- She is continuing the tap dance training she began bakke and Jack Borrok. in preschool and has also adopted jazz and ballet Jack enjoys listening (and singing along) to dancing. the Decemberists, and feeding baby guppies to his Team B-Cell was born to balance out ferocious fish, Gaylord Nelson. He has also initi- the Stem Cell Lounge. This group consists of ated the first Kiessling lab poker tournament. 31 Eric has gotten everyone in the lab, except April Samira Musah and undergraduate Pun Wang- and John May, addicted to the show, Battlestar kanont. Galactica. There is no change in Eric’s status as Love has certainly been in the air in the the go-to person and the know-it-all in the lab. Kiessling lab as Eric Underbakke is now mar- Richard Grant, Margaret Wong, and post- ried to Dipa Sashital and Jack Borrok is married docs Jiyoung Chang, and Yimin Zhu work, as to Roxanne Mitchell. John May will soon be Eric does, on protein modification. married to Kelly Gorres, as they have recently Erin McElroy and Grace Jiarpinitnun gotten engaged. work with Jack, Eric and Richard and Yimin on While we had some new additions, the chemotaxis and signaling. Kiessling lab has also had to say goodbye to David Peal has earned his PhD and requires friends Jessica Hollenbeck, Coby Carlson and that everyone first address him by saying, “Dr. Brendan Orner. All were post-docs in the labo- Peal, I am a mere underling and wish your ratory, or as we say, the lab elders. Jessica is now almighty wisdom.” an assistant professor at Trinity University in Post-doc Christine Brotschi returned to Texas while Coby is a researcher at Invitrogen. Switzerland to work in pharma research and Brendan is an assistant professor in Singapore. development. Although changes are inevitable, the The Kiessling group welcomes Eric Kiessling group remains close and is an awesome Kanugh, the new undergraduate in the lab. force in the Biochemistry department. We won Also new are Joe’s guppies, Nebby and Tammy the Christmas ornament contest of 2005, took and the 6 offspring that have been born, and first place in Egg Drop 2006 (thanks to the engi- Eric’s Betta splendens, Fighting Bob. New to neering genius of April and Rachael), and placed the Chemistry department are graduate stu- in the Halloween costume contest with Todd’s dents Aim Tongpenyai, Shane Mangold, Mexican wrestling alter ego, La Vaca Furiosa.

Since our last newsletter in April, 2006, three being, and instead is exploring other options, graduate students have moved on to their next including teaching chemistry and editing a jour- steps in life. Beth Thompson began her postdoc nal in education. The new people are settling in, in September 2006 in the laboratory of Dr. Sarah and the lab continues to be a fun place to do Hake in Berkeley. California. Dan Hesselson science. This is obviously the short version, so defended his thesis in June, was married Octo- please stop in to say hello and get really caught ber 8 in a wonderful ceremony here in Madison, up if you are in the neighborhood!! and began his postdoc in the laboratory of Dr. Here are some new email addresses: Judith Kimble Didier Stainier in San Francisco. Liana Lamont [email protected], Lab decided to punt on her postdoc for the time [email protected]

Greetings from the Lardy Lab! Our lab has been without grant support during Cards and letters from past colleagues added the past two years but we are now assured of cheer to our holiday period. Our current work- support beginning in February. Our most recent ers list is the same as last year and we are still paper acknowledges support, not from NIH, but working on exciting new steroids. More about from Myron Mehlman who has contributed that next year. generously to our work. Available funds will be The Biochemistry Department created a good news to Nancy Kneer who, in sympathy Henry Lardy Professorship and appointed Ron with our budget problem, reports only a small Henry Lardy Raines to it. Ron has a joint appointment as a fraction of the hours she works. Dr Padma Lab Professor of Biochemistry and Chemistry as Marwah published a paper (Bioorganic & Medic- does his wife Laura Kiessling—both are excel- inal Chem) in which she described the synthesis lent chemists. Laura holds the Laurens Anderson of 62 new steroids. That is one way to keep her Professorship. Many of you will recall that Andy bibliography number to a minimum. Dr Ashok was my first graduate student after having served Marwah and I have studied the conversion of in the Air Force during World War II. known natural steroids to new metabolites in 32 living rats. Caring for animals in Biochem is not battle. Her last weeks were spent at Hospice- a as convenient as it was before a Dean took our beautiful care center donated to the city by a space to create more offices. local family. Marion enjoyed the many visitors As time races by there are always sad events up to her last day. to report. Bert Pressman died as a result of an Both Annrita and I are enjoying good health, auto accident in June. Dave Garbers suffered are outdoors a lot, and proud of our fantastic a fatal heart attack this autumn. Jack Gorski, Grandchildren. I missed the Biochem meeting an Emeritus Professor of Biochemistry, with a in San Francisco this last year because our plane joint appointment in Animal Sciences, died a returned to Madison for repairs. We could not few months ago. Marion Wagner quit smoking have reached the meeting until after our Poster about 25 years ago but it was not soon enough day, so I cancelled. I hope to see you in Washing- to prevent the appearance of lung cancer that she ton DC in April of this year. fought bravely for many months. Throughout We wish you a very good New Year and that time Marion was cheerful and frank about invite you to visit! the limited time she had left before losing the

Comings and goings: on work Jürgen carried out at NMRFAM. Jürgen Anne Lynn Gillian-Daniel joined the lab as reported that he is now a homeowner and keeps an administrative assistant and is doing a great job busy running projects on structural biology and attending to details and helping us meet deadlines. plant isotopomer investigations. Greg Zorntezer completed his Ph.D. then stayed Meetings: on briefly as a postdoc with Brian Fox and John to John’s travels this year included two retire- complete studies of the dynamics of acyl acyl car- ment parties: one in April the day before the rier protein. Greg recently moved to a postdoctoral ENC at Pacific Grove in honor of Gerd LaMar, John Markley position in Michael G. Katze’s lab at the Univer- retiring from UC, Davis and one at Stanford in Lab sity of Washington, Seattle. Liya Wang completed October in honor of Oleg Jardetzky. There were his Ph.D and has taken a postdoctoral position three trips to Canada: to Banff for the advisory in Edgar Spalding's lab here in Madison. Young board meeting for the Human Metabolome Kee Chae arrived from Seoul with his family to Project, to Edmonton for a metabolomics con- spend a sabbatical in the lab. Young Kee will be ference, and to Toronto for talks in the Phar- working as a senior member of our metabolomics macy department and at Mitsu Ikura’s group team. Ed Mooberry seems to be enjoying retire- retreat (where John was invited to speak about ment and continues to help us out on high-pres- the “Early Days of Protein NMR Spectros- sure issues. Budget constraints at NMRFAM have copy”, proving how ancient he is). In Toronto, forced us to downsize the facility staff. This sadly John saw Fleming Hansen, who is a postdoc in led to departures of long term facility members Lewis Kay’s lab. John, Qiu Cui, and Ian Lewis Frits Abildgaard and Heike Blad. attended the Metabolomics Society Meeting in News from former lab members: Boston. They stayed at a B&B one block from Liz Farr sent word that she is working at an the apartment where John lived for 2 years as accounting firm in Albuquerque. She has a CPA a graduate student. At the meeting, they were license and is working on a degree as Certified pleased to see Jasna Fejzo and Mike Reily, who Valuation Analyst with the goal of a career in now work for branches of the same company. estate planning. Her eldest step-daughter made Another talk was at the First Annual Structural Liz a grandmother last October! She sends her Biology and Molecular Biophysics Workshop, greetings. John Newman reported that New York University of Nebraska Medical Center. John, City and his job are treating him well. John is an Eldon Ulrich, Jurgen Doreleijers, and Jikui Associate in Biotechnology at Merrill Lynch in the Song attended the ICMRBS meeting in Göttin- Big Apple. Congratulations to Rob Tyler, who is gen in August. John combined a Gordon confer- at the Medical College of Wisconsin, on receiv- ence in Aussois, France, with talks in Evry and ing an American Heart Postdoctoral Fellowship. Montpellier, where he visited Cathy Royer an Jürgen Schleucher recently sent greetings from old collaborator from UW. A Far East trip took Umeå, Sweden, along with a copy of a Ph.D. John to Beijing for the international structural thesis from one of his students, who followed up genomics meeting. Also at that meeting were

33 Dmitiry Vinarov and Qin (Kate) Zhao now Newman brought in 7 outside speakers and 26 representing Promega. In Beijing, they were hands-on attendees from 8 countries. The attend- royally entertained by Jinfeng Wang from the ees learned all the steps involved in going from Academia Sinica and her husband Zhenxi Wang DNA to protein in vitro. Similar workshops will and by Bin Xia. Then John flew to Tokyo for be held in 2007: contact us for details if you are a meeting of the Worldwide Protein Data Bank interested. (BMRB is a new member) and to Sapporo for Diane Sheehan had a show of her weavings two talks followed by a weekend excursion to hot at the new Watrous Gallery in the new Over- springs and volcanoes in southern Hokkaido. ture Center, mostly pieces produced on her new Other News: Jacquard looms that run on compressed air and CESG celebrated its 100th structure with a are computer controlled (one at her studio at cruise on Lake Mendota (see the photo). CESG home and one in the Department of Environ- and NMRFAM partnered to put on two highly ment, Textiles and Design, where she continues successful workshops. The workshop on “NMR to teach). Data Collection and Processing” (organized by Milestones: Anne Lynn, Milo Westler, Marco Tonelli, Klaas Claudia and Gabriel Cornilescu have a Hallenga, and Frits) brought in 11 guest speak- daughter Ioana born 10/21/2006. I-jin (“Jo”) ers from five countries and 37 attendees from 4 Lin and Jeng-Ya Yeh have a new baby girl, countries, including former lab members Josh Heidi, born 11/7/2006; with Zoe this makes Kurutz (Univ. of Chigago), Wen-Jin (Winston) two daughters. They are living in the Portland Wu (Academia Sinica, Taipei), and Enrique Oregon area.Congratulations to Zsolt Zolnai Melendez (Univ. of Puerto Rico). The workshop and Nevena Lucic who married last fall; Nevena on “Wheat Germ Cell-Free Protein Production” has landed a residency in internal medicine at (organized by Dmitiry and Carrie Loushin- Methodist Hospital in Brooklyn, New York.

It’s been a very busy year for us. Sarah and Omar time-dependent models of uranium reduction, are both doing prelims. Sarah, Raman and Steve Steve’s on predicting hot spots in protein-pro- have all been working on papers, and Roum- mel had two accepted. Roummel decided not to go to Louisville and stayed on as a Research Julie Mitchell Scientist. Sarah’s paper Lab is on recursive structures within biological pathways, Raman’s on 34 tein interfaces, and Roummel’s on methods for don on engineering new hot spots into protein clustering and optimization of protein docking interfaces. Steve is now going into the lab to test predictions. these experimentally. Mariko Hasebe has been We’ve also had a lot of undergrads work working with Sarah on categorizing the dynamic with us this year. Steve worked with three stu- behavior of recursive motifs in biological path- dents, Corina Prieto, Yinka Lesi and Brandon ways. Finally, Laura LeGault has been working Wanta. Corina looked into incorporating flex- with several of us toward the design of web-based ibility into hot spot predictions, Yinka and Bran- services for protein docking.

Greetings from the Ntambi lab!! degree in the United States. For the last part 2006 has been one of both continuity and of her Diploma degree, she is required to do change for the Ntambi lab as we persist in research on a small project for a period of six to trying to understand various aspects of carbo- eight months and present her results in a form hydrate and lipid metabolism using the stearoyl of a written thesis back home at the Nutritional CoA desaturase-1 (SCD1) deficient mouse as a Sciences department. Here in our lab, she’s model. been working on determining whether SCD1 Early this year, Dr. Weng Chi Man relo- deficiency alone in the liver can account for James Ntambi cated to Phoenix, AZ after receiving her Ph.D the enhanced insulin signaling observed in the Lab degree in December 2005. She later successfully global SCD1 deficient mice. found a post-doc position at the medical school As for other members of the lab—Dr. of Stanford University with Dr. Bertha Chen, Makoto Miyazaki, Dr. Matt Flowers, Dr. studying the molecular basis of diseases involv- Xueqing Liu, Harini Sampath, and Kiki ing changes in connective tissues such as stress Chu—each of us are continuing our research in urinary incontinence and female pelvic floor our respective projects including the regulation dysfunction, with the long-term goal of develop- of SCD1 by nuclear receptors and dietary fats, ing treatment for the patients. role of SCD1 in inflammation, and generation In May, Caroline Otzelberger from and characterization of various tissue-specific University of Hohenheim, Germany joined SCD knockout mice. Cora Holt our under- our lab to complete her research thesis for her graduate student continues to work with various “Diploma” degree. “Diploma” is an academic members of the lab to enhance her knowl- degree in Germany that resembles a Masters edge through first-hand laboratory experience. Thezin Chonyi is a hard-working high-school student who spends after school hours learning lab techniques. Last, but certainly not least, our mentor Dr. James Ntambi continues to juggle between many tasks, which consist of providing guidance to his students, speaking about SCD at various conferences around the world, and taking students on a 3-week long study-abroad program during the Winter break each year studying health and nutrition topics in the developing country of Uganda, Africa. His interntional work, and the program in Africa in particular, are described on page 13. We hope that you have enjoyed reading about us in this issue and wish you all the very best in your endeavors. 35 This year marks the sixth year that the Phillips No one can keep up with them and their new Laboratory has been in operation in Madison. discoveries. Computational studies related to Things are really moving along now, including structural bioinformatics are also in full swing. the graduation of Wisconsin Ph.D. students Dr. Postdocs Dr. Dimitry Kondrashov and Dr. Byung Wu Han (now a postdoc at The Scripps Demian Riccardi are busy connecting theoreti- Research Institute with Prof. Ian Wilson, Dr. cal predications of protein motions to reality, Euiyoung Bae (currently evaluating postdoc- graduate student Ryan Bannen is busy studying toral opportunities), and Dr. Jason McCoy (now connections between sequence, structure, and George Phillips a Genome Sciences Training Program Postdoc in dynamics. Roman Aranda, along with Elena Lab the Phillips Lab). Levin has been making experimental movies of The crystallography team associated with myoglobin in action, setting world records for the Center for Eukaryotic Structural Genomics, the generation of time-resolved atomic coordi- led by Dr. Craig Bingman and also comprising nates on the 100 picosecond time scale! We also Dr. Ed Bitto, Dr. Jason McCoy, bioinformati- welcome two new students to the Phillips labo- cians Dr. Xiaokang Pan and Dr. Gary Wesen- ratory family, Chris Bianchetti (a cajun, we love berg, graduate student Elena Levin, technician his cooking) and Aram Chang (who cooked up Louise Meske, computer systems administra- some new crystals on his first try) from the UW tors Bryan Ramirez and numerous enthusiastic Biophysics program, who will be working on new and energetic UW undergrads have deposited projects connecting protein structure, dynamics, about seventy-five protein structures in the Pro- and function. If you read this and have been in tein Data Bank and are really cranking in terms the Phillips laboratory in a previous life, drop of getting unique proteins crystallized, solved, in sometime, or at least keep us posted on your refined, and their functional relevance defined. whereabouts.

From modest beginnings here at the University Lee Zella completed her Ph.D. degree in of Wisconsin in July of 2001, the Pike labora- August of this year, and has elected to stay on tory has transitioned into a full-fledged member as a Research Associate. Sungtae Kim completed of the Department of Biochemistry. We can say his degree in November, and has taken a new with some certainty that we have made our final position at the Salk Institute in America's most laboratory move – not only to this university beautiful (and expensive) city, San Diego. We but to great digs on the 5th Floor of the New are anticipating that Mark Meyer and Jackie Biochemistry Addition where we now have con- Fretz will complete the work for their doctoral Wes Pike siderable space and, importantly, future room to degrees sometime this summer. Both of them Lab grow. Several members of the department call this have published papers under their “belts” and space the “Penthouse”. I can only say we do have we expect additional studies to emerge soon. a nice view of the lake, although a recent Bacte- Both Rob and Katie are the newcomers to the riology addition has obscured some of this gran- laboratory and are faced with taking Preliminary deur (not that we spend a lot of time looking out Exams this coming spring. Their research proj- the window). The laboratory has gone through ects are going very well, however, and thus we considerable growth as well as ebb and flow over expect their Prelim proposals to be well outlined, the past few years since the last report. We have well thought out and successfully defended. Dr. integrated a number of graduate students as well Hironori Yamamoto, a Research Associate from as postdocs and research assistants into the labo- Japan who helped us move from Ohio to Madi- ratory, and have graduated several as well. Aside son, and Dr. Makoto Watanuki, an orthopedic from the ongoing research that we have in place surgeon also from Japan, joined us several years in the areas of vitamin D and bone, perhaps most ago. Both have completed successful training exciting are some of the new research areas into programs here in Madison and have returned to which our current research has led us. their home country. Miwa Yamazaki, a Visiting Since coming to Madison, we have thus far Scientist from Professor Keichi Ozono’s labora- taken on the training of 6 Biochemistry gradu- tory at the University of Osaka, Japan also joined ate students, Lee A. Zella, Sungtae Kim, Jackie us at that time. Unfortunately, Miwa recently left Fretz, Mark Meyer, and most recently, Rob us for home as well. All of us thoroughly enjoyed Nerenz and Katie Bishop. Hironori, Makoto and Miwa’s stays in Madison 36 and their important contributions to the labo- is now in the hands of Melissa, Rob and Katie. ratory; they are missed greatly and will not be Lee used this technique of ChIP-chip screening forgotten. Thus, we now represent a highly undi- to identify the regulatory elements located in the versified laboratory. On the upside, Dr. Melissa vitamin D receptor gene that mediate autoregu- Martowitz recently joined us as a Research lation by 1,25(OH)2D3. This regulatory puzzle Associate, having completed a Ph.D. degree has existed since the mid 1980’s when we first with Dr. Emory Bresnick in the Department discovered that the vitamin D receptor autoregu- of Pharmacology here at the University. Melissa lated its own expression. As with the above find- was interested in the role of upstream enhanc- ings, these regulatory regions were found to be ers in the regulation of b-globin gene expression located within introns of the vitamin D receptor and her transition to the study of the mechanism gene over 30 kilobases downstream of the tran- of the regulation of RANKL gene expression scriptional start site. This discovery has prompted by the vitamin D hormone has been a relative a new approach by Lee towards characterizing easy one. As a Research Associate, Lee plans to the regulatory regions of the vitamin D recep- pursue, among other things, a characterization of tor gene. Finally, similar studies by Jackie led to the new regulatory regions within the vitamin D the identification of novel regulatory elements receptor gene that she has discovered. within the LRP5 gene, a gene which represents Our research continues to focus on the bio- a co-receptor for the Wnt signaling pathway logical and molecular actions of steroid hor- that functions in osteoblast differentiation and mones in the regulation of calcium homeostasis. regulation. Jackie continues this work as well as Of course, these studies focus primarily on the the research she has focused upon for the past actions of the vitamin D receptor, but also on several years aimed at delineating mechanisms the actions of both the estrogen and androgen whereby RANKL activates the process of osteo- receptors as well as the glucocorticoid receptor. clast formation. While many additional projects Surprisingly, our research has also led us into are ongoing, these findings represent the major studies of target genes for the hormone PTH as focus of our current efforts. well as the inflammatory cytokines such as IL- Of course, I have left out perhaps the most 1, IL-6 and TNFa and the cytokine oncostatin important change in our staff. Dr.Rupa Shevde, M. In brief, new genes have been identified that who accompanied me to the University of Wis- are key to the calcium homeostatic actions of consin from the University of Cincinnati and the vitamin D hormone in the intestine, kidney was instrumental in not only setting up the labo- and bone. These include the calcium ion chan- ratory but keeping it running smoothly for the nels TRPV5 and TRPV6 as well as the essen- past 5 years, left last year to take a position as tial osteoclastogenic factor RANKL. Using Senior Scientist and Group Leader at WICELL chromatin immunoprecipitation coupled to Institute. As many of you know, WICELL spe- DNA microarray hybridization (termed ChIP- cializes in advancing the development of the chip), Mark and Makoto identified and char- human embryonic stem cell technology pio- acterized the molecular mechanism whereby neered originally by Dr. James Thomson and 1,25(OH)2D3 regulates the expression of the now frequently in the national news. Rupa has intestinal calcium channel TRPV6. Surpris- long wanted to work in a different research set- ingly, this gene is regulated by at least 5 different ting where her numerous strengths could be DNA sequences, and Mark continues to explore put to a greater challenge and this seems to be their utilization in not only intestinal cells but emerging as the right place. She now teaches the bone cells as well. A more recent success has WICELL course in stem cell technology and a been the application of ChIP to studies in the short course on “how to” in human embryoid mouse intestine and kidney in vivo. At another body development. It is an exciting time, and level, Sungtae and Miwa screened the RANKL Rupa gets to meet scientists from all over the gene locus, identified and then characterized the planet who come to be trained in the art. Perhaps enhancers located upstream of the RANKL gene her most interesting challenge is as an advocate that mediated the actions of 1,25(OH)2D3. for science in Wisconsin public middle schools Interestingly, these enhancers were discovered to and high schools, where she works to excite the be located enormous distances upstream of the next generation of scientists. This type of work start site of RANKL transcription, opening up speaks to her greatest strengths. Nevertheless, we an exceptionally fertile area of novel research that miss her greatly in the laboratory.

37 Finally, new happenings are occurring on the Wisconsin. Our new laboratory, new students, personal front. Lee Zella was just married in and the excellent research environment created January, 2007, and has changed her name to by the faculty of this department are likely to Lee Ann Short. Mark Meyer is planning on get- ensure our success here in the future. We thank ting married, although his life changing event is Hector DeLuca for the role he played in getting scheduled for July. We wish them long and pros- us here. While we have much to accomplish in perous lives together with their chosen partners. the next few years, we are confident that this will In closing, I am very happy to be here in the be the place to do it! Department of Biochemistry at the University of

The Raines lab is in a dynamic steady-state, with Germany. Moushumi Paul is a Scientist at the eight people leaving the group in 2006 and eight USDA in her home town of Philadelphia. others joining the group. You can see all 25 of Arrivals. us at “work” in the most recent cartoon by our We are delighted that five graduate students artist in residence, Annie Tam. joined the Raines lab in 2006: Jimmy Hernan- Departures. dez and Mike Levine in biochemistry, Nadia Four graduate students successfully defended Sundlass in biophysics, Sayani Chattopadhyay their Ph.D. theses in 2006. Kim Dickson is now in organic chemistry, and Amit Choudhary Ron Raines an Assistant Professor at Macalester College in in physical chemistry. Mike and Nadia (like Lab St. Paul, Minnesota. Bryan Smith is a Scien- Rebecca Turcotte) are also in the M.D./Ph.D. tist at Deciphera Pharmaceuticals in Lawrence, program. Kansas. Steve Fuchs is a postdoctorate at the In addition, two postdoctorates crossed the University of North Carolina in Chapel Hill, Atlantic Ocean to join us: Daniel Gottlieb from and Eugene Lee will leave shortly for postdoc- Dortmund, Germany and Eddie Myers from toral work at Caltech. Bristol, England. Three postdoctorates also left us. Jason Thomas Baumann both arrived and Horng is now an Assistant Professor at the departed in 2006, spending a few months with National Tsing Hua University in Hsinchu, us as an “interdoc”. Thomas has now returned Taiwan. Thimmalah Govindaraju (a.k.a., to complete his doctoral work with Stefan Bräse Govind) is a Humboldt Fellow in Dortmund, in Karlsruhe, Germany (who sent us interdoc Christine Schilling in 2005). Couplings. Steve Fuchs and Erin Mettert (Kiley lab) got married in 2006. Kelly Gorres and John May (Kiessling lab) expanded a long-standing intergroup collaboration by announcing their engagement. Progeny. Rex Watkins and his wife Natalie brought Emilyn into the world. Frank Kotch and his wife Stefanie created Andrew. Armchair Sports. Thoughnew to the “sport”, Daniel captured the 2006 championship in the Raines lab Fan- tasy Football League, defeating sports veteran Rebecca Turcotte in the final round. Contact Us! As always, we are happy to welcome lab alumni to drop in for a visit and update us on life after the Raines lab. Or, see us at the March 2007 ACS meeting in Chicago. Otherwise, please send us an e-mail, and visit our lab website for more news: www.biochem.wisc.edu/raines.

38 It is with mixed emotions that I write my lab’s We are also back in the crystallography busi- news this year. Cathy and I are really looking ness. This has involved a collaboration between forward to our BIG move to West Falmouth, us (primarily Agata Czyz with help from Igor Massachusetts this summer, BUT, we love Madi- Goryshin) and Dima Klenchin in Ivan Ray- son and we have many great friends here. We ment’s lab. The goal is to explain why having a will miss living here. Within the Department it 5’ phosphorylated non-transferred strand has a is very, very tough for me. I cannot imagine a huge positive impact on strand transfer. Simplis- better place to have grown my career. Of course tic biochemistry would not predict an effect, but Bill Reznikoff the facilities, research opportunities and Uni- the structure demonstrates that the phosphate is Lab versity support have been great. But it is the likely important for moving the non-transferred friendships, colleagues and the special scientific end out of the way of the incoming target DNA. openness that I shall miss the most. Thank you Agata and Dima hopefully will also show us, for all very much. Of course my lab members will be the first time, a transposition complex with a especially missed. They are and have been great. bound transposition inhibitor. Currently the lab members include: Deb Hug, In addition to performing crystallography, who keeps the lab functioning; Igor Groyshin; Agata is using small molecule diketoacid inhibi- postdocs Agata Czyz and Soheila Vaezeslami; tors to study the details of how transposase works. and my last Wisconsin graduate student, Rich This has been a longstanding project in collabo- Gradman. Chris Adams defended this year, ration with Daria Hazuda’s group at Merck. It trecked around South America with Olivia and amazes me how 6 chemically similar inhibitors is now a Stanford post-doc. can have such different modes of action. This year has been great on the research Rich and Igor have had a very fruitful col- front. In a collaboration with John Marko (now laboration using genetic and biochemical analy- at Northwestern), Chris Adams set up a single ses to map out transposase residues important molecule system for studying Tn5 transposition. for target capture. The results make a beautiful We were uncertain whether the work would and somewhat surprising picture since residues just result in phenomenally beautiful pictures away from the previously proposed target bind- or whether we would also make fundamental ing region have the biggest effects. discoveries. I think that we have made impor- Soheila’s interests are in performing a satu- tant discoveries. A big thing that we discovered rated genetic / biochemical analysis of all trans- is that transposase forms catalytically inactive posase residues predicted to make DNA end complexes with non-specific DNA that are likely sequence contacts. This work should make a important in the biology of Tn5 transposition. major contribution to our structure function How does transposase “find” transposon DNA studies of the transposase. in a veritable sea of other DNA sequences? At My goals next year are to: set up a small lab least for short distances the transposon ends are at the MBL in Woods Hole in order to continue found through a direct transfer mechanism. How Tn5 studies, and to study the eating patterns does non-specific DNA participate in transposi- of Striped Bass and Blue Fish by fishing in the tion regulation? The non-specific DNA is a sink waters around Woods Hole. Who knows, maybe that inactivates the bulk of the transposase. the latter will turn into a genomics project.

We moved into 473 Biochemistry Addition— ison majoring in biochemistry and Spanish. He formerly Anant Menon’s lab—in July and have grew up in Crystal Lake, IL and bears a striking been busy building a lab, collecting data, and resemblance to Liam Gallagher from the British recruiting lab members over these past months. band Oasis. Let me introduce the current cast: Matt Copeland is a first year graduate stu- Basu Bhattacharyya hails from Madison— dent in biochemistry who grew up in Baltimore, he graduated from UW-Madison in 2005 where MD. Matt received his BS in biochemistry from he was a double major in biochemistry and McDaniel College in Maryland where he played Doug Weibel Spanish. Basu is currently a senior research assis- lacrosse (and led the team as captain) and col- Lab tant in the group and is in the transition between lected a large number of accolades. his undergrad and graduate education. Corinne Lipscomb is a first year graduate Charlie Burns is a sophomore at UW-Mad- student in chemistry who hails from Springfield, 39 IL. Corinne received her BS in chemistry from Hannah Tuson is a first year graduate stu- Manchester College in Indiana where she also dent in biochemistry. Hannah grew up in Yor- studied French and ran cross-country and track. ktown Heights, NY and received her BS in As an undergraduate student she studied organic biochemistry from Lafayette College in Pennsyl- chemistry in Paris. vania where she ran track and collected a number Sean McMaster hails from Kenosha, WI of honors. and is a freshman majoring in biochemistry and Doug Weibel is the PI. You can read more mathematics. about him in the article located earlier in this Joseph Molinda is a sophomore at UW- issue of the newsletter. Madison majoring in biochemistry. Joe played You can expect to see great science coming college football during his freshman year. (Atten- from this group of talented (and athletic and lin- tion faculty: Joe can be hired out to move heavy guistic) scientists in the near future. lab equipment. I charge only $50/hr.)

In the Wickens group, we work on how mRNAs that underlie repression. Starting with the yeast are regulated in animals. The biological impact S. cerevisiae, the threesome identified a spe- of regulation at the mRNA level now is incon- cific contact between a repressor bound to the trovertible. The control of translation, mRNA mRNA and to a specific protein in a large repres- stability and localization are important mecha- sion complex. From there, they showed that this nisms that help determine when, where and how mode of control likely was conserved through- much protein a gene produces. out the animal kingdom. Many of the same proteins control mRNAs Aaron and Brad are post-docs and con- Marv Wickens in embryos and the nervous system, and likely in tinue to focus on protein-mediated repression. Lab other somatic tissues as well. We want to know In recognition of the importance of his contri- how these regulators work, and what they do butions, Aaron was recently awarded the Paul in biology. We already know that the repressors Boyer Award, given to an outstanding post-doc- have vital roles in stem cells and learning and toral fellow in the department. He’ll be giving memory, and we are hoping to get a biochemical a departmental seminar this spring, and I am understanding of how they operate. already at work on embarrassing stories for his We focus primarily on proteins that bind to introduction. and control mRNAs: some repress, and some Daniel moved on recently to study biological activate. Over the last year, a trio of young sci- rhythms with Mike Young at Rockefeller. During entists in the lab, Aaron Goldstrohm, Daniel his last months in the lab, Daniel opened up a Seay and Brad Hook, took a major step for- new and exciting area concerning the function ward by identifying key molecular interactions of non-coding RNAs and intergenic transcrip- 40 tion. He still has a few experiments to do, but Jacque Baca, a grad student, is studying the end is in sight, even if it is crowded by the how proteins that recognize double-stranded bustle of Manhattan streets. RNAs contribute to mRNA control, and how Since I last wrote, Amy Cooke and JJ Chrit- they interface with other regulators. She has ton joined the lab; both are now second year been focusing on C. elegans, and appears poised students. JJ is trying to extend our biochemical to approach these issues. analysis to translational repression in vitro. We Fonda and Sinziana, two undergrads, help hope to recapitulate various forms of protein- support the entire research enterprise by prepar- mediated control in the test tube – the classic ing media, and buffers, and doing the glassware. biochemist’s approach – with an aim to identi- Marv Wickens, a professor, no longer even fying the key components and dissecting their remotely red-haired continues in much the functions. Amy has been working with the same same way as he always has. You can find him in group of regulatory proteins, but focusing on his office, enjoying the conversations with the how they control mRNAs during early develop- people who actually get things done in the lab, ment — and how that connects molecularly to fretting over some issue — scientific, meta-sci- what they do in adults. Her work has united her entific, or otherwise — or being helped by Carol with oocytes and embryos of the South African to remain on track and semi-in control and on clawed toad, which I am sure she will come to time, or wondering how his son, Zach, really is love (however frustrated they now periodically doing, or how those barnyard animals got loose make her). in the lab again. For those of you who remember RNA-protein interactions also are vital in Zach as a little red-haired bundle in Marv’s lap, regulation, as they determine which mRNAs that was 18+ years ago, and Zach has just begun are controlled. Laura Opperman, a grad stu- college at Macalester in the Twin Cities! Hard to dent, has learned a great deal about how one believe. Indefatigable, time. particular class of repressors that bind mRNAs I will not try to recapitulate all the highlights recognize their particular targets. The remark- of our illustrious alumni — there just are too able thing is the degree to which the interaction many good things going on. I will say that visit- is modular and rationally manipulable, at least ing my ex’s is wonderful. I had the great pleasure by Laura. She has now expanded her work from of in situ observations of three ex-students, Dave yeast to frogs, and then to mammalian cells. She Zarkower and Vivian Bardwell, at the Uni- would like to use rationally designed proteins to versity of Minnesota, and Jeff Coller, a brand target specific mRNAs for control at will. Craig spanking new faculty member at Case Western Stumpf focuses on the specificities and func- in Cleveland. A visit to Sunnie Thompson,now tions of RNA binding repressors in the worm C. in University of Alabama, is on deck. Here in elegans. Leah Gross, an undergrad, works with Madison, Mike Sheets and Catherine Fox are Laura to learn the rules of RNA recognition. thriving in the Biomolecular Chemistry Depart- Jae Eun Kwak and Labib Rouhana, both ment — and their young son Max is thriving grad students, have been focusing on activators even more, though he has lost Zach, a favored of mRNAs, and on a family of proteins that add babysitter. poly(A) to mRNAs in the cytoplasm. We discov- I am really tempted to say something about ered this enzyme initially in C. elegans, in collab- all of you here, because I love thinking about how oration with Judith Kimble; since then, we have all of you are doing, and picturing you again in identified counterparts in many other species, my mind’s eye, not just in the lab but off doing including humans. We now know a great deal your own adult (or pseudo-adult) thing. But that about how these poly(A) polymerases act and is not practical here. There are those of you scat- are controlled, and are exploring their biological tered around the globe and those in courtrooms, functions in Xenopus and Drosophila. Labib has those in the Senate and those doing post-docs, identified a positive-feedback loop in which the those who have joined faculties, and those who activator actually activates its own mRNA. are losing them, like me. You know who you are. Along the way, Jae Eun has identified yet Suffice it to say that I would love to hear another, new class of polymerases — these add from you, and even more, to see you. Come by poly(U), not poly(A), to their substrates. We are sometime, or drop an email, or a photo. You are dying to know what RNAs they control and how. always here anyway, even if you don’t know it.

41 Faculty Email & Telephone Numbers Rick Amasino...... [email protected] . . . . 608/265-2170 Aseem Ansari...... [email protected] ...... 608/265-4690 If you have questions or information Alan Attie...... [email protected] ...... 608/262-1372 please feel free to contact us. Sebastian Bednarek...... [email protected] . . 608/263-0309 Sam Butcher...... [email protected] . . 608/263-3890 http://www.biochem.wisc.edu Margaret Clagett-Dame.. [email protected] . . . 608/262-3450 Department of Biochemistry Mo Cleland...... [email protected] . . . . . 608/262-1373 University of Wisconsin–Madison Mike Cox ...... [email protected] ...... 608/262-1181 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 Perry Frey...... [email protected] . . . . 608/262-0055 Phone: 608/262-3040 Paul Friesen ...... [email protected] ...... 608/262-7774 FAX: 608/262-3453 Colleen Hayes...... [email protected] . . . 608/263-6387 Hazel Holden ...... [email protected] 608/262-4988 Change of Address, Information, Ross Inman...... [email protected] ...... 608/262-9881 and General Inquiries Laura Kiessling...... [email protected] . . . 608/262-0541 Cheryl Adams Kadera Judith Kimble ...... [email protected] ...... 608/262-6188 (608) 262-9835 John Markley...... [email protected] . . 608/263-9349 E-mail: [email protected] Tom Martin...... [email protected] ...... 608/263-2427 Julie Mitchell...... [email protected] . . .608/263-6819 IPiB Graduate Program Rebecca Montgomery..... [email protected] ...... 608/262-6773 Dave Nelson...... [email protected] . . . 608/263-6879 (Information and Applications) James Ntambi ...... [email protected] . . . . . 608/265-3700 Flavia Arana (608) 265-2281 Ann Palmenberg...... [email protected] . . . . . 608/262-7519 E-mail: graduateadmissions@bio- George Phillips...... [email protected] . . 608/263-6142 chem.wisc.edu Wes Pike...... [email protected] ...... 608/262-8229 Ron Raines ...... [email protected] ...... 608/262-8588 Undergraduate Program/Internships Ivan Rayment...... [email protected] 608/262-0437 Tom Record...... [email protected] ...... 608/262-5332 Dan Barnish (608) 265-9846 George Reed...... [email protected] ...... 608/262-0509 E-mail: undergraduateprogram@bio- Bill Reznikoff...... [email protected] . . 608/262-3608 chem.wisc.edu Mike Sussman...... [email protected] . . . . 608/262-8608 Doug Weibel...... [email protected] . . . 608/890-1342 Steenbock Symposia Marvin Wickens ...... [email protected] . . 608/262-8007 Chris Wiese...... [email protected] . . . 608/263-7608 Janice Carberry (608) 262-7129 E-mail: [email protected] Emeritus Gifts/Donations Julius Adler...... [email protected] ...... 608/262-3693 Laurens Anderson...... [email protected] . . . 608/262-3041 Please use the form at the right Helmut Beinert...... [email protected] . . . 608/263-6357 or go online to: Robert Burris...... [email protected] ...... 608/262-3042 www.uwfoundation.wisc.edu Alfred E. Harper...... [email protected] You may also contact the Chair: Paul J. Kaesberg...... 608/262-2205 Betty Craig Henry Lardy...... [email protected] . . . 608/262-3372 (608) 262-3040 Roland R. Rueckert...... [email protected] . . . 608/262-6949 E-mail: [email protected] Heinrich K. Schnoes...... 608/262-0650 John W. Suttie...... [email protected] . . . 608/262-2247

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Robert F. Aline, Jr. Herbert R. Heinicke Mr. and Mrs. Frank M. Reuter Marian T. Anderson Mark A. Hermodson Martin L. Ribovich Mr. and Mrs. Mark A. Ator Todd Joseph Holzbauer Jeffrey T. Richmond Walter M. Barker Rachel C. Houseman Robert E. Roberts Kathleen Ann Basmadjian Charles F. Huebner Alice V. Rohde Mr. and Mrs. Raymond E. Benenson Vivanti N. Jain Dr. and Mrs. Michael C. Roskos Mr. and Mrs. Duane A. Benton Ward W. Smith and Cheryl A. Janson Arthur G. Saponara Luke T. Bergerud Robert P. Hausinger Sylvia Z. Schade Joe M. Braun Dr. and Mrs. William T. Jackson Frederick J. Schendel Jeanne L. Bucsela Michael C. Janasik Saul A. Schepartz George E. Bunce Susan L. Kalvonjian Dennis W. Shepherd Gregory M. Campbell Donald A. Kita Dr. and Mrs. Charles F. Shuler James A. Campbell Mr. and Mrs. William F. Knilans Dr. and Mrs. Donald J. Siehr Douglas B. Chapman William E. and Anita J. Koerner David P. and Barbara L. W. Silva Ranjini Chatterjee Martin F. Kovacs, Jr. Paul A. Sims Peter T. Chivers Dr. and Mrs. Mei-Chang Kuo Thomas J. Skatrud Miriam De Salegui David O. Lambeth Donald E. Slagel Brian J. Destree William L. Leoschke Frederick G. Smith Mr. and Mrs. Edward M. Domanico Gerald Litwack Robert J. Lowe and Elena L. Spielman Lawrence B. Dumas, Jr. Jennifer M. Loeb Pari D. N. Spolter Jennifer Garvin-Cress Arnold S. Loo Joey M. Studts Barbara Gerratana Kelly M. Loyet Robert E. Stutz Margaret Gewont John E. Mazuski Duane A. Tewksbury Maurice Green Kenneth S. Meyer Nancy Torbet Mr. and Mrs. Kurt A. A. Grunwald Julia R. Montgomery James J. Vavra Sandra K. Grunwald John E. Morris Douglas E. Vollrath Glen E. Gutzke Mark A. Pallansch Theodore R. Watson David E. Hamer Richard B. Peterson William W. Wells Sylvia A. Hatfield Erik A. Petrovskis Ming-Chi M. Wu Keith F. Haviland Prof. and Mrs. Gregory D. Reinhart

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