UNIVERSITY OF WISCONSIN-MADISON 2006 NEWSLETTER

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

UNIVERSITY OF WISCONSIN-MADISON 2006 NEWSLETTER

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

Changes afoot, from Biochemistry Phase II to the New look of the Graduate Program...

It is a pleasure to together in contiguous space. !e negotiate the bureaucratic hurdles to write my first “from research space will include specialized establish an official new program. Tom the chair” dispatch areas for structural biology and chemical Martin and Sebastian Bednark, work- for the Biochemistry synthesis, allowing the department to ing with John Denu and Catherine UNIVERSITYNewsletter. OF WISCONSIN-MADISON It has stay at the forefront of emerging tech- Fox from Biomolecular Chemistry, been a busy and nologies. In addition, the building will spearheaded the effort. I believe that eventful year for the include much-needed state-of-the-art IPiB represents an unprecedented step department, as well lecture halls and teaching laboratories. in cooperation and collaboration in the 2006as NEWSLETTERfor me personally, Another priority in the department biochemical sciences at the UW. From the Chair as I “learn the ropes” has been the move towards a new grad- I hope you like the new look of our Betty Craig as chair. uate program - the “Integrated Pro- Newsletter and find the articles inside ForI am friends pleased of to reportthe Department that the Bio- gramof Biochemistry in Biochemistry” at (to the be called University informative. of Wisconsin-Madison We would be glad to hear chemistry Phase II Biostar Building IPiB) - a joint venture with the Biomo- from you anytime, and visit us when Project, our newest building to be cen- lecular Chemistry Department in the you can, to meet with old friends and tered on the present site of the 1956 School of Medicine and Public Health. see the changes afoot in Biochemistry wing, is moving forward. We are We think that the time for such a change for yourself. delighted that Flad and Associates, the has come. When the two departments designers of the 1998 Addition, have first established doctoral graduate pro- In this issue: been chosen as the architects. !e grams around the turn of the previous • A unique “hands-on” learning experi- design process should take about two century, these independent programs ence for undergraduates developed by years, with groundbreaking anticipated satisfied the separate need for special- James Ntambi that combines real-life in the spring of 2008. It will be a com- ized training in plant and animal bio- experience with classroom learning plex and challenging project, because of chemistry in CALS, as compared2006 to (page 3). the many physical constraints on the human biochemistry in the Medical • Establishment of two new professor- site. !e plan is to preserve the 1912 School. But, in the ensuing decades, an ships with a dual purpose – an oppor- wing and parts of the 1937 wing to understanding of the fundamental simi- tunity to honor two of our emeritus ensure the preservation of the Curry larities of biochemical processesNEWSLETTER in cells professors, Henry Lardy and Lau- murals (shown throughout this newslet- of all life forms has blurred the bound- rens Anderson, and to help retain ter). !e safety of the vintage elm tree aries between the research carried out two of our faculty, Laura Kiessling (aka Elmer) is also a priority. by students in the two graduate pro- and Ron Raines (page 22). !e new building will have labora- grams. • Efforts by faculty, particularly Mike tories for 20-24 research groups. !e So, the two departments crafted a Cox, to address issues of science edu- remaining labs still located in the old plan for a new joint graduate program, cation in secondary schools (page Enzyme Institute building will be inte- capitalizing on the strong history of 24). grated into the new building, as will all graduate training in both departments. • “Hector DeLuca on Vitamin D”, a the labs of the Biomolecular Chemistry Just weeks ago the two departments talk sponsored by the Wisconsin Department. For the first time the bio- recruited the first class of students for Academy of Sciences, Arts and Let- chemical sciences will be physically this joint curriculum, as we continue to ters (pages 26 & 27). Department of Biochemistry Alumnus by Bill Reznikoff Richard Scheller, Executive Vice-President for Research, Genentech, Inc. As a faculty, we all have a desire to help young Biochemistry at that time. Rich developed a students find and accomplish their life dreams. deep appreciation of structural biochemistry Some of our students come to the Depart- from that experience and was a coauthor of a ment of Biochemistry without a clear idea of paper from Sunda’s lab (Sprang, Scheller, where they want to go intellectually and pro- Rohrer and Sundaralingam. 1978. Journal of fessionally, while others know that they are the American Chemical Society 100: 2867- interested in Biochemistry and want to go on 2878). to be a scientist. Richard (Rich) Scheller is Rich’s interest in structural biology led in that latter group. him to go to the California Institute of Tech- nology so that he could work with Richard “I think that there are a lot of very dedicated Dickerson. It was during this time that he teachers at the University of Wisconsin. I thought manifested key features of his career; his great that the classroom lecturing was generally out- interest in exciting science and his ability to collaborate with a variety of investigators. standing. !ere were tremendous opportunities, During is graduate training at Cal Tech, Rich even at a large state school, to do individual re- worked with Art Riggs, Keiichi Itakura and search and an honors undergraduate thesis.” Herb Boyer. He made his mark at the time as one of originators of key recombinant DNA Rich came to the University of Wisconsin – techniques, but later worked with Eric Madison as a freshman in 1971. He had Davidson’s lab as his interests changed to grown up in Milwaukee with a passion for using the technology to study developmental science in general and biochemistry in par- biology questions using the sea urchin as a ticular. By some good fortune for me, he was model organism. assigned to me as an advisee. I do not know Rich then went on to work with Richard whether I had an impact on him, but I do Axel and Eric Kandel at Columbia Univeristy remember that I thoroughly enjoyed the rela- – Physician and Surgeon’s Medical School for tionship. Rich was a very successful student a postdoc. Rich was the molecular biology who worked hard because he loved the adven- bridge that led these two labs to use recombi- ture of science and he loved learning new nant DNA technology to start studying things. He was a thoroughly fun person to molecular neurobiology using the marine snail interact with. He recently gave the University Aplysia as a model organism. !is is the field the best compliments that we could receive. that he continued to pursue as a professor at “I think that there are a lot of very dedicated Stanford University, at first in the Biology teachers at the University of Wisconsin. I Department, and then in the Department of thought that the classroom lecturing was gen- Molecular and Cellular Physiology and the erally outstanding. !ere were tremendous Howard Hughes Medical Institute. opportunities, even at a large state school, to In 2001, Rich became the Director of Sci- do individual research and an honors under- entific Research at Genetech. Currently he is graduate thesis.” Rich took advantage of the the Executive Vice President for Research. His research opportunities open to undergradu- scholarly contributions have been recognized ates by first working in the laboratory of Ray by numerous honors including his election to Brown in the Oncology Department and the American Academy of Arts and Sciences then in the laboratory of Muttaiya Sundaral- and to the National Academy of Sciences. All ingam in our Department. Dr. Sundaralin- those who know Rich, know him as an excit- gam was the lead X-ray crystallographer in ing, fun person who still loves science.

2 Study Abroad in Uganda – International Health and Nutrition by Professor James Ntambi Billions of people face pressing health and nutrition issues that seldom confront most Americans. James Ntambi, Professor of Biochemistry and of Nutritional Sciences, College of Agricultural and Life Sciences (CALS), has initiated a program to help educate UW students about these world- wide problems. He does so by taking a group of students from UW-Madison to Uganda, “!e Pearl of Africa,” to learn first hand about the many health and nutrition 2006 students issues faced by people in a developing students develop a better understanding of not-for-profit student organization called country. !e “Uganda Study Abroad: Inter- the many health and nutrition issues that the Village Health Project-VHP (www.vil- national Health and Nutrition” program confront most Ugandan's. !ese questions lagehealthproject.org) and applied and offers exciting opportunities to learn about then form the framework for the course as obtained two Wisconsin Idea Undergradu- these issues from a classroom perspective well as the 3-week field experience in ate Fellowship grants from the Morgridge and through real world experiences. Uganda. Examples of some questions stu- Center for Public Service to help imple- !e program is the outgrowth of a part- dents consider are: What are common ment rural water projects. VHP also works nership between CALS and Makerere Uni- nutritional deficiencies in developing coun- with an AIDS support organization to versity (Uganda’s premier institution of tries? Why do people have vitamin defi- purchase ribbons for sale back here at UW- higher education) in Kampala, Uganda. ciencies? How do economics affect health? Madison, with the proceeds supporting Professor Ntambi, the program’s creator What are the impacts of the HIV/AIDS HIV/AIDS positive clients and other and leader, hopes that as future health care epidemic? Why has Uganda been so suc- health related activities in Uganda. providers, these participants will some day cessful in its fight against this disease? What With his colleagues in Uganda and at lend their expertise to addressing these are the relationships between nutrition and UW-Madison, Professor Ntambi has cre- problems. He believes this exposure will infectious diseases – most specifically ated a program that is making a difference make them better health care providers, related to children? for UW students interested in health whether they eventually work overseas or In Uganda, Professor Ntambi and his careers. !e program really makes “the in Wisconsin. As Professor Ntambi states, colleagues at MUIPH arrange learning world their classroom,” and clearly dem- “You cannot experience a situation like visits to rural health centers, Mulago Hos- onstrates that UW-Madison is not only a Uganda and not become a more caring pital (the National referral hospital), HIV/ world-class, but also a world-involved uni- and therefore more effective health care AIDS clinics, child nutrition centers and versity! It is the Wisconsin Idea gone inter- provider!” homes in rural villages. Professor Ntambi national. Professor Ntambi, along with John Fer- also makes a strong connection to the rela- If you wish to contribute to this pro- rick, CALS International programs office, tionships between health and food; how it gram, please see page 31 for more informa- work closely with colleagues at Makerere is grown, stored, and consumed. Field- tion. University and in particular the Institute of trips to agricultural research stations, Public Health (MUIPH) on course content farms, and local markets highlight these and in developing the experiential learning relationships. opportunities during the 3-week field study !e program began in the fall of 2003 in Uganda. During the fall course that pre- with twelve students and has grown to fif- cedes the winter break overseas experience, teen. In response to needs identified by students returning from Uganda, the program now includes a service- learning component that is helping to address Completed water tank with homeowners the lack of access to clean water–a signifi- cant problem in Uganda. With Professor Ntambi as their faculty advisor, in 2005 stu-

dents formed a 501(c) 3 plaque Dedication John Kakitahi James Ntambi John Ferrick Markerere University Dept. of Biochemistry CALS International 3 Programs Office Faculty Research Spotlight by Aseem Ansari Simple synthetic molecules orchestrate a genomic symphony

Starting as a single fertilized cell, a human being we should be able to reassemble a live transcrip- made of billions of very different cells eventually tion factor from simple synthetic modules. takes form. All cells contain the same genome, Our early results were extremely encourag- but "specialize" to acquire diverse shapes and ing. By linking a small DNA-binding ligand to a functions. !e genome itself is an inert reposi- short designed peptide, a molecule emerged that tory of information, an extremely large encyclo- specifically recruits the transcriptional machinery, pedia written with just four letters. How is the thousand times the size of our synthetic molecule, information read to orchestrate such a complex to a targeted promoter. Using this same logic, we and precise transformation? now want to manipulate genes that are of central !e genomic encyclopedia is selectively importance in human development and disease. accessed, and the information guides the fate of We have begun by focusing on the Homeobox cells. Different parts of the encyclopedia define (Hox) family of transcription factors. different fates and numerous cues impinge on Hox proteins have a DNA binding domain the cell to direct it to utilize information in that is conserved from bacteria to man. In specific chapters. !ese cues instruct regulatory nearly all multicellular organisms these proteins proteins to bind specific sites in the genome control genes and regulatory networks that are and to regulate the expression of target genes. critical for axial patterning and segmentation !us, these regulatory proteins, known as tran- of the organism. In humans, several Hox pro- scription factors, play a central role in cellular teins also play a role in hematopoiesis and their physiology. !e importance of their roles is clear malfunction is thought to facilitate the onset of in all organisms. In humans, their malfunction several leukemias. underlies numerous diseases, including cancer We chose to focus on two key members of and diabetes. this family, Ultrabithorax (Ubx) from the fruit My lab is focused on understanding how fly Drosophila melanogaster, and HoxB1 from transcription factors stimulate the transcrip- humans, because they are critical biologically, tion of targeted genes. As a post-doctoral and because a great deal is known about how fellow, I began to dissect transcription factors they work. Both of these Hox proteins bind using chemical and biological methods. Our specific DNA sequences in combination with work, and that of other labs, showed that another DNA binding partner. !is partner is the factors were amazingly modular called extradenticle (Exd) in flies and Pbx in - lego blocks that can be mixed and humans. After examining the crystal structure of matched in many combinations. the complexes, we thought we could build syn- Now, we try to recreate func- thetic molecules that would have the DNA rec- tional molecules using syn- ognition properties of Hox proteins (Ubx and thetic counterparts. Our HoxB1) and, via a small hook, would be able to reasoning is that if we recruit the partner Exd/Pbx1 to a specific DNA truly understand site. We collaborated with Peter Dervan's group how the pro- at California Institute of Technology to generate teins work, the compounds. !ese synthetic Hox-mimics work surpris- ingly well. !ey bind specific DNA sequences and recruit the natural Hox partners Exd/Pbx1 to DNA. Interestingly, the human Hox partner is critical for pre-B cell development (hence its name Pbx) and it often is altered due to aber- rant chromosomal breakage-and-reattachment in pre-B cell leukemias. !e chromosomal translocation leads to the creation of an abnor-

4 mal protein that is a potent transcriptional information provides invaluable insight toward activator of genes that trigger unbridled cel- the design of synthetic molecules that function lular proliferation. When these genes are with high degree of precision. expressed in an unregulated manner they lead In the long term, we hope to generate molecules to the onset of acute lymphocytic leukemia. that can trigger different genes and networks We now are trying to create artificial transcrip- in a pre-ordained manner. Along the way, we tion factors to combat this oncogenic form of surely will need to manipulate their potency Pbx1. !is is a significant challenge: the mol- and specificity, and learn what networks they ecules must traverse the cellular membrane, activate and how. As our understanding of these enter the nucleus, and act as we command. process increases, we hope to design molecules What is more, they must not only be potent, that trigger specific differentiation pathways. but specific. !e basic approach could be used to guide the A key facet of transcription factors is their fates of stem cells and treat several terrible dis- cooperative assembly on specific DNA sites. We eases. !e applications to personalized thera- have learned new rules that govern these inter- peutics and tissue engineering are far off, but actions, including the role of allosteric modula- in getting to that distant target we will also gain tion of DNA structure in cooperative assembly significant insights into regulatory networks of several factors. Using a new microarray-based that govern cell fate. Ultimately, we hope to approach that was developed in our lab, and engineer cell fates by choreographing transcrip- named CSI:Madison by my students, we can tional networks. We want to design precision- comprehensively define the DNA recognition tailored chemicals that read desired articles of properties of our synthetic molecules as well the genomic encyclopedia, and direct cell fate as that of the natural proteins. Such textured in a predetermined manner.

In Memoriam: 2006

Arnold, Aaron (PhD 1937 Elvehjem) October 29, 2004

Hankes, Lawrence Valentine (PhD 1949 Elvehjem) December 16, 2004

5 Center for Eukaryotic Structural Genomics – Protein Structure Initiative by Donna Troestler and George Phillips !e Center for Eukaryotic Structural Genomics Biochemistry and Biomolecular Chemistry and (CESG) was founded by John Markley, Brian Shen and !orson from Pharmacy. Collabora- Fox, and George Phillips and is in its 5th year, tions with other faculty members are underway. and Phase 2, of the the NIH’s Protein Structure Currently, we are collaborating with Prof. James Initiative (PSI). During the five-year pilot phase !omson to solve structures of proteins he and of PSI, the $270 million given to nine U.S. cen- others identify as potentially playing key roles in ters resulted in more than 1,100 solved protein the differentiation of human stem cells. We are structures, of which more than 700 were unique, already nearing the end of our first year of PSI-2, and numerous technical advances (see PSI Pilot and to date we have deposited an additional 21 Phase Selected Technical Advances at the end of structures (91 total) into the Protein Data Bank this article). (PDB). During the pilot phase, CESG received a Later this year, for space and planning purposes, four-year, $17 million grant, and its primary CESG’s protein production laboratory will move efforts were centered on setting up a protein pro- to the old Genetics building on Henry Mall. We duction pipeline with requisite staff and equip- will occupy the entire fourth floor of the build- ment. With essential support from Biochemistry ing, and a large portion of the 3rd floor. It has Department staff and collaborators, CESG suc- been a lengthy process to clear out the areas we cessfully implemented a pipeline, and went on to will occupy and to prepare the space for CESG solve 61 structures, primarily from Arabidopsis labs, as the rooms and labs were outdated and in thaliana.!e second phase of the NIH project, need of many repairs. We hope to move by the PSI-2, supports four large-scale and six special- end of summer, 2006. CESG’s X-ray crystallog- ized U.S. centers. !e four large-scale centers are raphy team will remain located at the Phillips expected to generate between 3,000 and 4,000 Lab, and the NMR teams will remain located at structures. CESG has become a “Specialized the Markley Lab and in Prof. Brian Volkman’s Center,” with the explicit mission of developing laboratory at the Medical College of Wisconsin. novel methods for quickly determining structures CESG is conducting a workshop with of proteins that traditionally have been difficult NMRFAM this summer. !e 2006 CESG/ to study. !is effort has received $20 million of NMRFAM Wheat Germ Cell-Free Protein support from NIH. Production Workshop will be held from July !e CESG now is focusing on proteins from 30, 2006, to August 4, 2006, and will offer 25 many eukaryotes, including human, mouse, rat, participants a unique opportunity to obtain yeast, zebrafish, thermophilic algae, and others. hands-on experience with cell-free protein pro- Its goal is to obtain approximately 20% of our duction from wheat germ extracts. It will cover structures from outside requestors, so we wel- various aspects of small-scale expression screen- come suggestions of proteins whose structures ing and large-scale production of labeled proteins would make a large impact on a particular for NMR spectroscopy or crystallization screen- research area. CESG publications that have ing. Both manual and automated procedures will appeared or are in progress include as coauthors be covered. several UW-faculty members, including Raines, For more information on the workshop, CESG, Palmenberg, Butcher, Brow, Denu, Frey, Ray- and CESG structures, visit our website at: ment, Holden, Phillips, Fox, and Markley from http://www.uwstructuralgenomics.org

6 2” Schematic diagram of a custom 24-hole aluminum A shaker platform rack equipped to secure polyethylene terephthal- ate (PET) 2-liter beverage bottles in high-throughput protein pro- Selected Technical Advances from CESG: duction in refrigerated floor shaker (CK 25C Series, New Bruns- 8” wick, NJ, USA). • !e “Sesame” Laboratory Information • Incorporation of a wheat germ cell-free 8” 9.375” 2” 2.5”

0.5” Management System allows users to enter, expression system (developed at CESG in col- B DC process, view, and extract relevantE data from laboration with Prof. Y. Endo, Ehime Univer- any location using a series of Web-base appli- sity and Cell Free Sciences, Yokohama, Japan) 2” 2.5” cations. holds the promise of increasing the produc- • Auto-induction protocols allow4.375” automatic tion of proteins from higher organisms.

19” induction of bacterial protein production. • Automated software for X-ray crystallo- !ese protocols produce 10 times more pro- graphic structure determination can carry tein per volume of culture than traditional out fully automated determination of three- methods. dimensional protein structures from X-ray F 1” • Custom expression vectors that provide0.375” diffraction data. 1” 2” target protein fusions that promote total • Automatic crystal mounting and crystal expression,28.5” enhance solubility, and permit screening robots use computational pro- 1.25” 0.5” G 5.75” rapid detection by fluorescent tags. !ese cesses to automatically screen crystals for A - Front & back 2 @ 8” x 28.5” x 1/16” vectors can be used to engineerB - Left proteins & right ends toand center dividersquality or for contiguous collection of mul- 2” Himprove their folding and solubility. 4 @ 8.5” x 20“ tiple data sets. H (scored and bent to 90° on three sides) 2” • Auto-induction protocols allowC - Shelf automatic brackets 24 @ 1” x 2” •x 1/4”!e interaction between various pieces of lab D - Bottom 1 @ 19” x 28.5 x 1/16”” induction of bacterial proteinE - Shelf production. 4 @ 9.375” x 18.8125 x 1/8”equipment, a bar code writer, and a personal (left and right sections) !ese protocols produce 10 times and more 2 @ 9.3125 pro- x 18.8125 x 1/8”digital assistant through a wireless computer (center section) tein per volume of culture thanF - Shim traditional clips 192 @ 3/8“ x 1” network allows for inexpensive, small-scale G - Bottom assembled showing sections walls (B) methods. and mounting washers (F) in placeautomation of a lab environment and can • A fully integrated robotic crystallizationH - Mounting washers 4 @ 2” x 2” x replace0.25” the old-fashioned laboratory note- system can set up a 96-well plate every 2 book. 9.5” minutes,9.5” giving it a9.5” maximum throughput of • Automated NMR data analysis is a fully 2,880 different crystallization experiments integrated data analysis platform that pulls per hour. together the complete process of protein • Storage and crystal imaging units can NMR structure determination and analysis, quickly image 96 wells of a crystallization as well as archiving raw NMR data and inter- plate. mediate results. • Small-volume crystallization chips, now • Automated post-structure functional anal- used widely by crystallographers, are used to ysis software is used to search a three-dimen- screen conditions efficiently and speed crystal sional structure against databases of growth. three-dimensional structural templates and identify functionally important motifs. A Web interface for the software has been designed, and it can be used to obtain a sum- mary of a protein’s most likely function.

7 From the Covers Ron Raines Wickens Marv Poly (2S-proline) forms a left-handed helix that is the most stable The specificity of a regulatory protein in the C. elegans germ- structural element attainable with a natural polypeptide. The stability line (photography by Sarah Crittenton, image design by H. of this polyproline type II helix is enhanced by installing an electron- Adam Steinberg). withdrawing substituent in the R configuration at C y of the proline residues, as in this model of [(2S,4R)-4-fluoroproline]10 (photogrpa- hy by Robin Davies, image design by H. Adam Steinberg). Alan Alan Attie Hazel Holden Electron-microscopic image (40,000x) of a pancreatic β-cell N-acetyl galactosamine kinase (GalNAc kinase) is an ATP-depen- (upper left) and a fenestrated endothelial cell forming the wall dent enzyme that catalyzes the production of GalNAc-1-phosphate. of a micro-capillary. Insulin-containing secretory granules can Crystals of the human enzyme were grown in the presence of its be observed in the β-cell, with one showing evidence of a recent substrates, MgATP and GalNAc. As can be seen from the electron fusion with the β-cell surface membrane resulting in the disper- density (mesh), the enzyme is active in the crystalline state and the sion of insulin into the extracellular space (photography by Ben products of the reaction, MgADP and GalNAc-1-phosphate, are August, image design by H. Adam Steinberg). observed in the active site (image design by H. Adam Steinberg). 8 Sam Butcher Ron Raines Structure of the HIV frameshift site RNA (PDB ID 1Z2J) Disruption of shape-complementarity markers to create cyto- with artistic rendering of an approaching ribosome (image toxic variants of ribonuclease A (image design by H. Adam design by David Staple and H. Adam Steinberg). Steinberg). Ron Raines Rick Amasino Proline residues are especially common in the triple helix of Leaf senescence is a developmental program in which nutrients are collagen, which is the most abundant protein in animals. Both recycled. In deciduous trees, such as this maple, nutrients are moved predominant pyrrolidine ring puckers of proline are displayed from the leaves resulting in beautiful fall colors. The nutrients are in a 2-azabicyclo[2.1.1]hexane residue, which thus provides stored in the stem and roots and, in the following spring, are used new insight on the effect of ring pucker on collagen stability to support a new crop of leaves (photograph by Jordan Hall). (image design by H. Adam Steinberg). 9 From the Covers Ann Ann Palmenberg Sebastian Bednarek HeLa cells infected with encephalomyocarditis virus (EMCV) and har- The cover image is a SEM micrograph of the stigmatic surface of a wild-type Ara- vested at 2 (top left), 4 (top right) and 6 h (bottom) post-infection. Cells bidopsis flower (face-on view). During flower morphogenesis, the stigmatic papillae were fixed, permeabilized and stained with anti-3D antibodies (visualizing expand anisotropically to form elongated cells that serve as a receptive surface for EMCV 3D polymerase). Then the cells were incubated with anti-mouse pollen grains. Polar expansion of adl1A stigmatic papillae was inhibited, and the FITC-conjugated antibodies and TxR-conjugated wheat germ agglutinin, mutant cells showed defects in cell wall formation and plasma membrane recycling localizing Golgi and nuclear membranes (by Aleksey Aminev, Institute for (photography by James Busse, image design by Robin Davies). Molecular Virology). Ron Raines Record Tom Interactions in the complex of ribonuclease inhibitor The relationship between salt bridges on the surface of DNA-binding pro- and ribonuclease A. teins and the formation of extensive (wrapped) protein–DNA interfaces. Salt bridges between cationic and anionic sidechains observed in the X-ray structure of lac repressor and a track of cationic sidechains wind around the protein exterior, plausibly defining the DNA wrapping interface and trajectory in the global wrapping mode. Upon binding, some or all of 10 these salt bridges are proposed to break, profoundly affecting the observed thermodynamics of binding (image design by Ruth Spolar and H. Adam From the Labs This past year, Cupid entered our laboratory and ting into all kinds of trouble -- in a good way. Jon- went on a shooting spree, striking 6 members of athan and Dani miss Madison and WI very much. our laboratory. Angie, Donnie, Matt, Jessica, !ey’ll be in Alaska this summer for 2 months Oliver, and Phil all got married. where Jonathan will be working in one of the big Our diabetes work is progressing quite well. hospitals serving the Native American population We got our diabetes genetics NIH grant renewed – “Ive always wanted to see a larger population of with a fantastic priority score. Our manuscript folks enriched for the “thrifty genes” we’ve always reporting our first positional cloning success, a talked about.” new diabetes quantitative trait locus, was accepted Dan Gretch is now an Associate Professor at Alan Attie in Nature Genetics. We also published an expression Montana State University-Billings with tenure. Lab QTL study in PLoS Genetics, a syntergistic collabo- “A year ago, I changed research focus from things ration between our group and our wonderful statis- that clog your arteries to things that put holes tician collaborators, Christina Kendziorski, Brian in your brain. I transitioned into the world of Yandell, and Christina’s student, Meng Chen. prion research and received 5 years of funding Summer is in her third year of graduate through the NIH INBRE program. My research study in the lab. Highlights from the past year has allowed me to cut my teaching back to 50% include a visit to the Petersen Lab at the Univer- (mostly biochemistry for science majors and nurs- isty of Aarhus, Denmark, and passing her prelim ing students). Darla is doing well and is still work- exam in late April. She continues to be an active ing in the investment world. Brice is now in high member of the department, sitting on the student school (which he loves), is driving a car (yikes) faculty liaison committee and playing on depart- and won the Montana state high school wrestling mental kickball and dodgeball leagues. Summer championship as a freshman. Brad is now in sev- looks forward to an upcoming vacation to Disney enth grade and is doing great in school and in bas- World. and the biochemistry lecture/laboratory ketball and football as well.” courses for the nursing students in the spring. “I Scott Cooper and his wife Amy continue to will also be participating in an interdisciplinary enjoy life in western Wisconsin. !e highlight of learning community this fall that will link stu- last year was attending a research symposium in dents in astronomy, physics, chemistry, biology, Cairns, Australia. !ey worked in a stop in New sociology, and political science. Our theme will be Zealand to sea kayak, and some diving on the great sustainability.” barrier reef. Scott’s 5th and 6th graduate students Oliver and Summer are working closely finished in June, and his first graduate student, together on angiogenesis in relation to pancreatic Tim Walston, finished his Ph.D. and got a teach- islets. !is is an exciting and challenging new area ing job at Truman State University in Missouri. for our lab. Oliver has done some of the work in Don Gillian-Daniel is keeping busy as zebrafish in collaboration with Mary Halloran’s the Assistant Director of the Delta Program in lab, and we’re correlating some of the phenotypes Research, Teaching and Learning where he coor- of our congenic mouse strains with those we see in dinates their teaching internship program for the zebrafish. graduate students and post-docs. Each spring he Matt graduated and is now a post-doc in James teaches metabolism in the Vet School, something Ntambi’s lab. Jessica will graduate this summer he began doing many years ago while a post-doc and then do a Nutrition clinical internship. Hong with Alan. On the home front, Ben (5 this April) left us to take a job at Schering-Plough working and the Hannah and Noah (2 in June) keep Don on drug targets in pancreatic islets. and Anne Lynn, well, very busy! In news from lab alumni, Scott Lowe, who is Kim Dirlam-Schatz was promoted to Asso- now a Howard Hughes Investigator, won the very ciate Professor at the end of the 2003-2004 aca- prestigious Paul Marks Prize for Cancer Research. demic year, but then took the next year off to be Jonathan Stoehr has another year in his residency home with her second child, born at the end of program at Yale and will be Chief Resident next September 2004. She returned again last fall and year. His daughter, Maddy (3), has memorized has been teaching part-time (50%) since then. a half-dozen bedtime stories and likes to “read” She currently teaches a laboratory course for non- books to her little brother. Jackson (18 mo) is get- majors in the fall. 11 Wedged between the Markley and Fox groups on RNA structures recently solved by NMR, includ- the first floor is a shady enclave of miscreants that ing the U6 RNA stem-loop and its RNA binding study RNA structure and function. Please don’t protein partner Prp24 (Reiter), the frameshift be too afraid of this den of rabble-rousers. !ey site RNA of HIV-1 (Staple), the U2-U6 spliceo- are actually a nice group of people once you get somal RNA complex (Sashital), and the notori- to know them. Some of them have even started to ously large tetraloop receptor complex (Davis). openly admit that proteins are interesting. Alto- !ese talented students will confess to conspir- gether there are 10 of these rogues, sometimes ing with John Markley’s NMRFAM gang (Blad, referred to collectively as “!e Butcher Lab.” Abildgaard, Cornilescu, Westler and Tonelli to Sam Butcher Individually, they have many aliases but are most name a few). If you go looking, I am sure that Lab commonly known as: Nick Reiter, Dipa Sashi- you can find these people lurking in the base- tal, David Staple, Jared Davis, Ryan Marche- ment at odd hours. schi, Sarah Pillard, Vincenzo Venditti, Trent In this past year, the ringleader of the Butcher Foster, Allyssia Borski and Sam Butcher. lab was promoted to Associate Professor with Rumor has it that as many as four Butcher tenure. Tenure is a euphemism for “keep doing lab members may fly the coop with Ph.D.s in science but spend more time in committees.” the near future. Be on the lookout for Staple, Nevertheless, if you would like to visit the dark Reiter, Sashital and Davis to take their turns in side of biochemistry, pay a visit to 141 Biochem- the hot seat as they defend themselves (they are istry Addition. We have a Warden (Rita Warden) expected to sing like birds). On exhibit will be and if you look OK, she just might let you in.

Yong Liu graduated with her Masters in John Marlier and his wife and daughter spend the December. She moved to San Francisco with her summer in Madison, with John determining the husband, Kaisheng (post-doc Frey lab, now has isotope effects on the urease-catalyzed hydrolysis a job at Amgen), and their daughter, Miranda. of formamide. Jill Rawlings was also here during Jeremy Van Vleet, a fourth year graduate the summer. student, is getting married in March to Jennifer Mo now has two NIH grants, one joint Headman, a graduate student in the bacteriology with two colleagues in Australia, John Wallace department. in Adelaide and Paul Attwood in Perth, to study Laurie Reinhardt Mo Cle- , assoc. scientist, and her pyruvate carboxylase. Mo visited the University husband Eric Steinmetz had their second son, of Florida (and the Sarasota Opera) in March and land Tyler Hudson, on April 18th of last year. Logan State University in August (also the Utah Lab Mark Anderson, asst. scientist, finished our Summer Festival Opera). 2005 was a big year for joint isotope effect study of dihydroorotase with Mo’s family. His older daughter, Elsa, had a boy, Richard Christopherson in Sydney, Australia, Maxwell Cleland Niles, in May, and his younger and a paper is now in press at Biochemistry. daughter, Erica, was married in Whistler, British Columbia, in July.

12 Current Lab News: home in their beds, an undergrad working in the Vessela Petrova has joined the lab as a gradu- lab, Reece Goiffin, came to the rescue. !e Bio- ate student. Vessela got her B.A. in Biochemistry chemistry building was badly damaged but thanks and Molecular Biology at Franklin and Marshall to Reece’s efforts in alerting other lab members, College. She surprised us on March 1st when she no equipment in the Cox lab was damaged. presented the lab with a red and white doll. Ves- Mike is having an even busier year than usual. sela explains that in Bulgaria, martenitsas (the In addition to the never-ending book writing, he red and white dolls) are exchanged on March 1st organized a UCLA (Keystone) symposium held to celebrate the coming of spring. Usually they’re in Taos in February, and is organizing a session at Mike Cox worn until the first stork or a blossoming/leafing the ASBMB meeting in San Francisco in April. Lab tree is seen, then they’re tied to a tree branch. Architects are being chosen for the new Biochem- Our martenitsas is attached to the Cox lab news istry building project just starting up, that he will board instead of a tree and I think we’re look- be overseeing. He is helping to spearhead efforts ing for a robin instead of a stork. !e lab has to create two new courses in the department (one over looked this celebration of spring since Mara on Molecular Evolution for undergraduate non- Robu’s tenure. Welcome to the lab Vessela! majors, and a professional development course !e Cox lab also has a new postdoc. Dmitry for first year graduate students). He will also be Baitin joined the lab in December 2005. Many an instructor in a course this summer in Corsica, Cox lab members may remember that Dmitry has sponsored by the French Centre National de visited the lab twice before as part of the Fogarty Recherche Scientifique. Somebody has to do it. International collaboration between Mike Cox and Research in the lab is going particularly well. Vladislav Lanzov who’s lab is located in St. Peters- Watch the literature over the next year for new burg, Russia. Welcome back to the lab Dmitry. Cox lab contributions. Our research program is Rachel Britt has her preliminary examina- evolving. tion scheduled for April 2006. !e Cox lab has submitted its first bill to the Past Lab News: Wisconsin State Assembly! Mike and several col- Li-chun Huang sent a note saying that she’d leagues advised Representative Terese Berceau in traveled to China for the first time in Novem- crafting a bill that was introduced to the Wiscon- ber 2005, and that they’d got around by foot, sin legislature on February 7, 2006. !e aim of the bike, train, bus, and boat. She said it was quite Science Education Protection Act is to defend the an adventure. She also mentioned that she’d integrity of science in the state’s science classrooms. climbed Mt. Whitney August 2005. !ey’d com- Our fingers are crossed! A more detailed descrip- pleted the 6,000 foot climb, 22 mile round trip tion of the bill and related efforts in the depart- in 12 hours. !at’s something! ment can be found elsewhere in this newsletter. Nami Haruta wrote to say that she was On a cold Wisconsin Saturday night, a sprin- making a move from Yokohama City University kler pipe in the 1998 Biochemistry Addition burst to Osaka University. She said she was to continue around 1 . While the grad students were at her research of S. pombe Rad541 and its media- tors after she’s relocated.

Awards: Julia Cox received a Peterson Fellowship for 2005-2006. Julia Drees received a Steenbock Fellowship for 2005-2006. Julia Drees also received a Vilas Travel Award for the Keystone meeting in Taos, New Mexico, in February 2006.

Goings: Shelley Lusetti has accepted a position of Assis- tant Professor at New Mexico State University, Las Cruces. Congratulations, Shelley! We’re all excited for Shelley but will certainly miss her.

13 Michael Hobbs will be defending his thesis works, she has back up plans to visit her grand- spring 2006 and plans to work in the Madison mother in Australia over the summer, and then to area. join the Brenda Bass lab at the University of Utah Julia Drees defended her thesis this May and as a postdoc working on RNA editing enzymes. is currently deciding on a postdoc. Julie Eggington will defend her thesis spring Weddings and Babies: 2006 and (per Julie) has plans to start her own Julia Drees married Erin Chalmers in August of reality TV show called “!e Hot Room: P32.” 2005. !e wedding was held in Santa Cruz, Cali- Should her TV pilot not be picked up by the net- fornia, near where Julia is from. Nami Haruta married Satushi Takahashi in April 2005 at the Kamigamo-Shrine. Nami sent photos of the wedding and she was beautiful in her white kimono. Congratulations Nami and Satushi. Nami and Satushi also gave us the news that they’ve just had a baby! Nami sent a picture of Kazume who is extremely cute. What a lot of life changes for Nami in the past year. Congratu- lations on your new baby too! Tanya Arenson and Paul Marrione sent us news that they’ve just had a new baby boy who they’ve named Jonathan. Jonathan was born on March 8, 2006. Congratulations to you both on the new addition to your family.

Besides continuing to publish, review, travel, organic chemistry. “My biggest fear is that my teach, and keep an eye open for WMDs, here son [James] will grow up with a Texas accent,” are some of this year’s activities, accomplish- she says. Elissa Hobert, who is about to choose a ments, plans and quotes from the Laura Kiessling graduate school, works with Jessica. Meanwhile, Group. Brendan Orner plans to leave April 15 to be an Newly crowned Lab’s Most Quotable Person assistant professor at Nangyang Technological is grad student Adam Courtney with, “Why do University’s Division of Chemistry and Biologi- you have to make this a house of lies?” and this cal Chemistry in Singapore. “I’m going to take unrelated declaration: “I don’t conform. I defy snow tires with me because I heard you can’t get Laura Kiessling the Microsoft Word spell checker on a regular them there,” says Brendan. Lab basis.” Postdoc Coby Carlson, who plans to Ashley Reinke, who works with Eric land a job in industry in 2006, welcomed a baby Underbakke, will begin the biomedical sciences daughter in June 2005. Maeve joined big brother program at the University of Michigan. Eric is Cian, age 4. Grad student Ratmir Derda was on engaged to Dipa Sashital of Biochem Associate TV for 5 seconds, looking in a microscope when Prof. Sam Butcher’s lab. He says, “Just let them “60 Minutes” interviewed Prof. James !om- know I’m still alive and kicking.” David Peal, son. !is month Ratmir will present “High who plans to earn the Ph.D. soon and move to !roughput Approach to Functional Materials Utah for a postdoc position in Alejandro San- Supporting Human ES Cell Self-Renewal” at the chez’s group. !ere he will chop up worms (pla- American Chemical Society’s spring meeting in naria) and study regeneration. Erik Puffer will Atlanta in an Excellence in Graduate Polymer earn the Ph.D. soon and start a job with the Flow Science Research Symposium. Laura will pres- Cytometry core at H.L. Moffit Cancer Center in ent similarly at the Materials Research Society’s Tampa, Florida. Katie Alfare received a gradu- meeting. Grad student Lingyin Li and postdoc ate research fellowship from the National Sci- Brendan Orner also contributed to the stem ence Foundation. Katie is a member of Graduate cell work. Postdoc Jessica Hollenbeck is leav- Women in Chemistry, a relatively new group on ing this summer to be an assistant professor at campus formed in response to high attrition rates Trinity University’s Department of Chemistry among female scientists. !ai scholar Aimon in San Antonio. She will teach biochemistry and Tonpenyai is being mentored in the lab until 14 early June by graduate students Emily Dykhui- Alumni news: Eva Gordon is a science writer zen and Grace Jiarpinitnun. Aimon is earning for the new ACS Chemical Biology Journal. Erin her B.Sc. in chemistry from Mahidol University. Carlson is at Scripps Research Institute in a post- Emily was awarded a fellowship from the Divi- doc position with Ben Cravatt. Jason Pontrello sion of Medicinal Chemistry of the American landed an academic position as assistant professor Chemical Society. Postdoc Christine Brotschi in chemistry at SUNY Cortland. Andy Spencer from Switzerland extended her stay in the lab, joined “a good group” at protein Design Labs at happily. She plans to seek a permanent position San Francisco after reluctantly leaving the Khosla soon. John May, who is enjoying being a new lab in Palo Alto last summer. ChemoCentryx is dissertator, posits, “Adam tries to imitate my the site for new work in medicinal chemistry for accent when he wants to sound intelligent.” Bill !omas. Zhi-Qiang Yang has also taken an Grad student Jack Borrok’s contribution to industrial position at Merck, West Point. Robert the newsletter: “If Todd Gruber ‘borrows’ my Owen began work in March as a principal sci- pipette one more time and doesn’t return it, I’m entist at Pfizer in Ann Arbor, Michigan. Yi He going to go medieval on him!” Todd is safe at took his new Ph.D. to work for 3M Biosciences. the moment. He is at Applied Molecular Evolu- At Yi’s graduation, we heard great testimony tion in La Jolla, California, as part of a 12-week from former group member John Phillips. Just internship under the Biotechnology Training remember that what you say in the lab can come Program. !is year Todd married Corey Last- back to haunt you. Our favorite thing about inger and adopted a beagle mix named Penny. Yi’s new job is his title: Biochemist. Will Sand- Emily Dykhuizen did an internship last year with ers recently moved to Tetrionics (in Madison), Abbott Laboratories as part of her BTP program. which was acquired by SAFC. Will’s title is not Grad student Erin McElroy and postdocs Jiy- “biochemist.” Allison Lamanna is a postdoc- oung Chang and Yimin Zhu substantially round toral fellow in Michigan with Rowena Matthews; out the group’s roster in the chemistry lab. Patricia Mowery is enjoying her time as a post- Laura hired Sally Garbo Wedde as an editor doctoral fellow in Utah with Sandy Parkinson. to assist her with new duties as editor-in-chief John Phillips is in the Stoltz Group at Caltech of the new American Chemical Society Chemi- working on the total synthesis of the natural cal Biology Journal (http://pubs.acs.org/jour- product bielschowskysin, which has been identi- nals/acbcct/currentissue.html). !e third issue is fied as a potent inhibitor of EKVX lung cancer under way. !e journal is accompanied by online cells. Jason Gestwicki is working on recruiting podcasts and a Wikipedia feature that encour- students to Michigan (we still like you Jason), ages the science community to discuss chemical as a member of the Department of Pathology. biology and thereby help define it. Also new to Michelle Soltero-Higgin and Josh Higgin (for- the group are grad students Rachael Carpen- merly of the Raines lab) welcomed a baby boy. ter, Richard Grant, Becca Splain, April Weir Ross Weatherman, an assistant professor in the and Margaret Wong. Rachael named April the Department of Medicinal Chemistry at Purdue, group’s “most fashionable.” April is engaged to is a new father. Nikki Pohl gave an outstanding UW-Madison physical chemistry grad student seminar in the Department of Chemistry. Nikki Jeremy Higgins. Rachael says of Sally, “It seems has already been promoted to associate profes- that everyone is vying to be her favorite and Joe sor with tenure. A grad student in the Chem lab, Klim apears to be in the lead.” Sally disavows Lingyin Li, initiated a collaboration with lab any notion of favoritism. At this writing, post- alum Andy Hinck, an associate professor at the doc Matt Allen was debating whether to bring a University of Texas-San Antonio. watermelon to the Great Dane when he dresses Kiessling Group members have been as Gallagher to compete for the title of `Stache out on the road. Matt presented on contrast Master of Madison. !e contest is the annual agents for MRI synthesized using ROMP at finale to four weeks of mustache-growing for the the “Imaging in 2020” conference Septem- fundraiser he started with 3 other Kiessling group ber 25-29, 2005, in Jackson Hole, Wyoming. members. Fellow lab member Richard Grant is Ratmir and Erin Carlson attended the meeting participating, too. Mustaches 4 Kids Madison “When Chemistry Meets Biology” on the Greek (http://www.m4kmad.org) last year raised more Island of Spetses. Coby Carlson attended the than $3,000 to help the Make-A-Wish Founda- AACR-NCI-EORTC International Conference tion fulfill wishes for children with life-threaten- “Molecular Targets and Cancer !erapeutics” ing medical conditions. in Philadelphia in Nov. 2005. Jessica went to 15 the Protein Society meeting in Boston and the and India’s Council on Scientific and Industrial National Meeting of the American Chemical Research (CSIR) successfully held their first joint Society in Washington, D.C. Ron Raines and conference titled Building Bridges, Forging Bonds Laura also spent some time at the meeting in for 21st Century Organic Chemistry and Chemical Greece. !ey can confirm that Erin and Ratmir Biology, at CSIR’s National Chemical Laboratory were at the sessions and not on the beach. !eir (NCL) in Pune, India, on Jan. 7–9. A follow-on daughter, Kyra, made a very interesting poster for mini-symposium was held at the Indian Insti- the meeting. Laura also visited Bordeaux, France tute of Chemical Technology (IICT) in Hyder- this summer to give the Tetrahedron Young abad Jan. 11–12. Bob Grubbs, this year’s Nobel Investigator Award Lecture. After the lectures, Prize winner, enjoyed it when Kyra asked him she had a chance to sample some of the local if he was the Dumbledore of chemistry. Laura wines. Unfortunately, the maximum number of recently returned from a trip to England as the bottles that can be transported to the U.S. was Rosalind Franklin lecturer. Until the missed con- 2, so there was little benefit to the group at large. nections at the end, the trip was delightful —the Laura, Ron and Kyra also attended Pacifichem night spent in the Ramada Inn outside the Mall in Hawaii, followed by a jaunt to India. ACS of America detracted a bit.

Over the past year, a lot has happened in the as a postdoc with Xin Sun to work on vertebrate Kimble lab. On the science front, we continue to development. Beth has not yet decided where she explore the regulation of germline stem cells as a is going, but plans to delve into the mysteries of model for controls of stem cells more broadly in plant development. Finally, Kit Tilmann com- animal development. Our most recent results are pleted his postdoc last summer, and started as an taking us in several exciting directions, includ- Assistant Professor at Loyola University in Balti- ing analyses of a novel β-catenin, cyclin D as a more, Maryland. developmental coordinator and the CEH-22/ In addition to these big professional moves, Nkx2.5 homeodomain transcription as a deter- there have been an unusual number of marriages, Judith Kimble minant of the stem cell niche. In addition, we engagements and new babies. Kit Tilmann and Lab have uncovered a gradient of FOG-1/CPEB that Megan Kenney have become engaged, as have controls germ line proliferation at one level and Dan Hesselson and Stephanie Nelson. Liana spermatogenesis at another, as well as a role for Lamont and Scott Meade were married last PUF-8 in control of the sperm/oocyte switch. year, as were Mike Chesney and Tristana Von In 2005, Trey Kidd and Jen Bachorik both Will; Kellee Siegfried and Matthew Harris have finished their Ph.D.s, and in early 2006, Liana become parents to Lily Anne Harris, who was Lamont and Beth !ompson followed suit born July 6, 2005. More recently, Nayoung Suh to defend their Ph.Ds. Trey and Jen have both and Euiyoung Bae gave birth to Subin Hannah moved on to life as a postdoc: Trey to Duke Uni- Bae on March 23 at 1:31pm, 2006. Remark- versity to work on zebrafish development in the ably, Trey Kidd and Mindy Steiger became new Poss lab, and Jen to the University of Pennsylva- parents only a few hours later: their son, Henry nia in the Dryefuss lab. Liana is staying in Madi- Justus Kidd was born on March 23, 2006 at son, but will move to the Genetics department 4:11pm. All are doing well.

16 Despite the various departures over the last year, So those are the major headlines. !e news- we also have some recent additions: several new letter mafia is restricting size of the contributions graduate students, John Jeong, Aaron Ker- this year, so I will leave it at that. But of course schner, Josh Snow and Dyan Vogel; a post- there is much more. So please stop in to say hello doc, Olivier Cinquin; and a technician, Maya and get really caught up if you are in the neigh- Fuerstenau-Sharp. Olivier is delving into the borhood!! mechanism by which size of the mitotic region Here are email addresses of the people is controlled, and plans to model that regulatory who have left the lab over the past year. trey. network mathematically. !e others are just get- [email protected]; bachorik@mailmed. ting started. upenn.edu; [email protected].

Greetings from the Lardy Lab at the Enzyme cians to test 16α-hydroxyDHEA as a treatment Institute! We have had some very good let- for Respiratory Distress Syndrome in premature ters from alumni and find that more and more babies. !e 16-hydroxyDHEA makes a 15-fold of you are retiring. One who is not retiring is rise in the last days of normal pregnancy and Shelly Schuster. Last year I mentioned that he preemies have very little of it. Giving the babies had become President of a new graduate school glucocorticoids induces the lung secretion but in California. It is named the Keck Graduate also retards brain development. So I think the Institute and trains students in the combination natural lung maturing agent is the 16-hydroxy Henry Lardy of Biotechnology and Business. !e grads have steroid and it should be tested. We have no funds Lab gone on to dozens of companies and universities. for trials and the lab operates on a combination Contributors to his Institute have been gener- of modest royalties on 7-oxoDHEA and my sav- ous—it grows! ings. Scientifically we have not advanced far since We have a new post-doc in our group—Dr. last year. I wrote a review on C19,∆5 steroids for Nianjun Xu. He brings his own salary from Vol. 71 of Vitamins and Hormones; Padma has China! Nancy Kneer has Emeritus status and synthesized about 60 compounds searching for participates by conducting enzyme assays and anti-androgens that might be useful in treating literature searches. Marion Wagner is seriously prostate cancer; Ashok has completed analyses afflicted with lung cancer. Her medications have of blood samples for a pharmacokinetic study not been effective so she has stopped taking them. of ADEK, our best-so-far anti-androgen. He, Yet she is very cheerful and still enjoys activities together with Padma, is also continuing the char- with friends. If you wish to send cards or letters acterization of steroids produced from DHEA by her address is: 12 Westbrook Circle, Madison, liver and brain tissue—some 30 compounds to WI 53711 go! We have been unable to get any clinicians We look forward with eager anticipation to to test ADEK on CaP patients or any pediatri- the first Tuesday in November 2006!

Comings and goings. Ed Mooberry retired last bodan Macura and Nenad Jurinac at the Mayo February after 24 years of service to NMR at UW- Clinic College of Medicine. Craig Newman Madison. We threw a “recognition reception” for left NMRFAM/CESG to take a position with Ed on March 3rd to send him off in style, and Epic Systems, a medical informatics company the Biochemistry faculty voted unanimously to that must be the fastest growing enterprise in grant Ed emeritus senior scientist status. Hee- the Madison area. Chris Oldfield, a Biophysics Chul Ahn, a postdoc in NMRFAM, returned to Training Grant trainee, has moved to Indiana Korea to direct the laboratory at KIST in Seoul University Purdue University at Indianapolis to that has a new 900 MHz NMR spectrometer. work with Keith Dunker, who is a collaborator John Markley Before leaving, Hee-Chul published a paper in on the CESG (Center for Eukaryotic Structural Lab JACS on the structure of crambin in a mixed Genomics) project. Qin (Kate) Zhao moved aqueous/organic solvent and in DPPC micelles; from CESG to Promega. John Cao moved from part of his project was in collaboration with Slo- CESG (Sesame) to a position with the State of

17 Wisconsin Corrections Division. Muniasamy son Brock last May. Rob Tyler and John were Neerathilingam (“Munish”) joined the lab as a speakers at an NMR workshop at Montana postdoc in NMRFAM after finishing his Ph.D. State Univ. in Bozeman last August. Andy Rob- under Iain Campbell at Oxford. András Perczel ertson, the new Chief Scientific Officer for the from Eötvös University in Budapest is a visiting Keystone Conferences, wined and dined Eldon professor at NMRFAM on a Fulbright Grant. Ulrich and John last January and gave them Jing Li has remained with the Sesame project a tour of the Robertson ski chalet in the Key- but moved from support from CESG to support stone area. Sue was back in Iowa City, where the from our NIH-funded metabolomics project girls (Kelly and Sarah) are finishing school. !e family comes together in Colorado for vaca- News from former lab members: tions. Young Kee Chae picked John up at the From “Viru” Virudachalam: "Sen is a 3rd year Seoul Airport last February and gave him a tour med student at Penn State, Vanitha is a 4th year of Sejong University, where Young Kee is an undergrad, applied math, at UC-Berkeley. Subbu Asst. Prof. Young Kee brought his graduate stu- continues to work in cancer research and I am dents to the meeting in Daejeon, Korea, where quite busy and active in implementing new treat- John gave a talk. Although Byung Ha Oh, ment modalities in our clinic." (Viru is Chief professor at Pohang University in Korea, could Physicist of Radiation Oncology at JMMD not attend the meeting, he gave his greetings to Health System in Concord, California.) Jane John by telephone. One of the highlights of the Caldwell and her husband Tim stopped by for a Korean trip was a day of skiing at Muju--John’s brief visit last summer; Jane is enjoying her work first experience of skiing in Asia. in the Dept of Biology at West Virginia Univer- sity in Morgantown. Dagmar Truckses and her Other News: husband Nate (geologist at ExxonMobil) have a Zsolt Zolnai is continuing to develop his 2-year old toddler daughter, Tatjana, who “loves “Sesame” laboratory information management to imitate her mama and talks lots,” Dagmar system. New users include one of the specialized works with Ray Jacobson, Asst. Prof. at the MD structural genomics centers supported by the Anderson Cancer Center in Houston, and was NIH Protein Structure Initiative and a structural recently promoted to the position of ‘Instructor.’ genomics group in Australia. Bill Walkenhorst, Chair, Chem. Dept. at Loyola Univ., New Orleans, and his family were refugees Milestones: of Katrina. !ey got out before their house was I-jin (“Jo”) Lin passed her oral prelim last flooded and moved in with family upriver in St. December. She has taken a postdoctoral position Louis. Tim Machonkin is moving to a faculty at the Oregon Health & Science University in position at Whitman College in Walla Walla, Portland, Oregon. Dmitiry Vinarov and his wife Washington. We heard from Chele DeRider Sara had their second child (a girl). that she was looking for jobs in the East Coast. Where did you land, Chele? Rob Tyler left CESG Family News: to take a postdoc position with Brian Volkman John and Diane’s son. Andrew. graduated from at the Medical College of Wisconsin. Andrei Carnegie Mellon University (Chemistry Major) Alexandrescu has been promoted to Assoc. Prof. last May and has started graduate school at the at the University of Connecticut, Storrs. Brian University of California San Diego in Chemistry Volkman has been promoted to Assoc. Prof. at and Biochemistry. !eir daughter, Jessamyn, is a the Medical College of Wisconsin. Anne Lynn graduate student in Biology at the University of Gillian-Daniel is doing a great job as the new Utah in Salt Lake City. administrative assistant for NMRFAM. John’s travels: Greetings: John and his son Andrew took a boundary Best wishes to all. Please keep in touch. Waters canoe trip with George Reed and his

18 Greetings from the Ntambi Lab! !is year has (Biology) who are all working with various mem- been one of both continuity and change for the bers of the lab to further their knowledge through Ntambi lab as we persist in trying to understand first-hand laboratory experience. Soon, we are to various aspects of carbohydrate and lipid metabo- be joined by the youngest member of the team, lism using the stearoyl CoA desaturase-1 (SCD1) !ezin Chonyi. !ezin is a high-school student deficient mouse as a model. who will spend some of his after-school hours in Over the past year, we have had to bid good- the Ntambi lab. bye to two of our lab members, Dr. Agnieszka As for the rest of us veterans of the Ntambi James Ntambi Dobrzyn and Dr. Weng-Chi Man. Dr. Dobrzyn lab, we continue to delve into our respective Dr. Makoto Miyazaki Lab returned to her hometown of Bialystok, Poland projects. has been instru- in November of 2005 and is now heading up her mental in the development of various tissue-spe- own lab there. Dr. Man was awarded her doc- cific SCD1 knockouts. He has also characterized toral degree in December of 2005 for her thesis the phenotype of the SCD2-deficient mouse and on “Topology of SCD1 and its co-localization investigated differences in substrate specificity with DGAT-2 in endoplasmic reticulum.” She is between various SCD isoforms. currently in Sunny California as she starts a Post- Harini Sampath continues to make prog- doctoral position at Stanford. ress in her thesis project aimed at understanding With these two departures, we have also had how various dietary fats differentially affect lipid the pleasure of welcoming two new members metabolism and risk for obesity and insulin resis- to the Ntambi Lab. Dr. Matt Flowers, whom tance. She is also mentoring Andres Abreu, a many of you may have seen roaming the corri- senior undergraduate student who is collaborating dors of the 5th floor, has now decided to roam with her on understanding differences in insulin them on the 4th floor instead. Matt was awarded sensitivity in various mouse models of obesity. a Nutritional Sciences NIH-training grant and Kiki Chu is also continuing her thesis proj- has begun work on characterizing various tissue- ect in understanding the role of SCD1 in lipid specific SCD1 knockouts in the Ntambi Lab. metabolism, particularly looking at its effect on Dr. Xueqing Liu, or simply Liu as we know hypertriglyceridemia and liver steatosis and its him, has joined us from the Jefcoate lab in the regulation by certain nuclear receptors. Pharmacology department at UW-Madison. Liu Last, but certainly not least, our fearless mentor obtained his doctoral degree at Ohio University Dr. James Ntambi continues to provide guidance and is now interested in understanding the role to his protégés despite a rather hectic schedule. of inflammation in regulating hepatic function. Dr. Ntambi continues to be invited to speak about We are also joined by three eager undergrad- SCD at various conferences around the world. uate students Andres Abreu (Zoology), Cora Furthermore, the partnership that he has estab- Holt (Biochemistry) and Amanda Doubleday lished between Makerere University in Uganda and the University of Wisconsin-Madison has flourished. !is year alone, fifteen undergraduate students from diverse disciplines made the 3-week long, 15,000-mile trip to get a first-hand glimpse at some of the problems that face the other half of the world we live in. With this project in Uganda, Dr.Ntambi has begun to bring much-needed attention to the issue of undernutrition, which is certainly something that is often forgotten in our quest to understand the consequences of overnu- trition. All the members of the Ntambi Lab hope to join him soon in this venture to bring aware- ness to problems that should really be obsolete by now but unfortunately are not. We hope that you have enjoyed reading about us in this issue and wish you all the very best in your endeavors. Cheers!

19 As we in the Raines lab continue to assault the forward to getting married this summer. Eugene interface between chemistry and biology, a mul- Lee continues to resist late afternoon naps while titude of changes have taken place. Brian “gene” preparing for his thesis defense and applying Miller, our cloning expert, left to become an for postdoctorate positions. Bryan “chum- assistant professor at Florida State University in mer” Smith, who recently became a father and Tallahassee. Kim Dickson is now an assistant pro- defended his thesis, is seeking an industrial posi- fessor at Macalester College in St. Paul, MN, and tion in Nebraska to return to his roots and teach already has several undergraduate students work- his daughter Ava the true meaning of “country”. ing in her laboratory. Betsy Kersteen works for After working with Kim Dickson for several Ron Raines the local biotechnology company, Eragen Biosci- years, undergraduate Bernie Fula, is now pursu- Lab ences. Matt “Popo” Soellner has migrated west ing a career in medicine at the UW School of to take a postdoctoral position with Jon Ellman Medicine and Public Health. Melissa Yatzeck, a at the University of California, Berkeley. Other senior, is taking some time off to take care of her lab alumni have also joined the ranks of assistant newborn baby girl, Mary. Shawn Lin, a junior, professors: Chiwook Park at Purdue University, continues to work with Jeremy Johnson after and Sang-Hyun Park at Seoul National Univer- a humanitarian trip to New Orleans. With the sity. And, Jin-Soo Kim left ToolGen—a com- departure of Julia Tretyakova to New Mexico, pany that he co-founded—to become a professor former student hourly Greg Jakubczak, alias at Seoul National University. LMJ, has enthusiastically taken over as the new !e Raines lab retirement community— Raines lab manager. Caitlin Dallich, who makes the 5th floor of the 1985 wing—had its grand a mean Tris buffer, is the new student hourly in opening this year with three senior lab members the lab. moving to that comfortable clime. Steve Fuchs New graduate students and postdoctor- defended his thesis successfully, and will move ates are picking up where others have left off. south at the end of summer to take a postdoctoral !is year the Raines group welcomed first-year position with Brian Strahl at the University of graduate students Greg Ellis, Nicky McElfresh, North Carolina at Chapel Hill. Steve also looks and Rex Watkins. Rex and his wife are expect- ing their first baby—a girl—and we wish them the best of luck. !e Raines lab also welcomed two postdoctorates to the lab. Moushumi Paul, who considered becoming a roadie for Toad the Wet Sprocket, received her Ph.D. with Wilfred van der Donk at the University of Illinois and is working on secondary structure stabilization of ribonucleases. Margie Borra the co-founder of the Bay of Pigs, received her Ph.D. with John Denu in biomolecular chemistry and is work- ing to characterize a novel human ribonucle- ase. Postdoctorates Matt Allen (Caltech) and !immaiah Govindaraju ("Govind") (NCL, Pune) are working jointly with the Kiessling and Abbott laboratories, respectively, on projects that can only be called “interdisciplinary.” Luke Lavis, a third-year student, passed his prelim exam and continues to develop novel fluorogenic probes to aid the group’s cell biol- ogy efforts. Joe Binder, an all-star cross-coun- try runner, proudly displays lab mottos on his fume hood while applying olefin metathesis to proteins. Matt Shoulders, a second-year stu- dent, enjoys working with acetyl chloride, eating Indian buffet, and listening to country music. Annie Tam, a fourth-year student, has the most artistic fume hood in the world of chemistry,

20 and has developed a reagent that unites the Cindy Chao and Rebecca Turcotte are work- Staudinger ligation and expressed protein liga- ing hard on their prelims. Rebecca is pursuing tion. Postdoctorate Frank Kotch recently syn- a joint M.D./Ph.D. degree and is in her fourth- thesized both “human” collagen and his first year overall. Fourth-year grad students Jeremy baby—a boy, whose gender was revealed conclu- Johnson and Jeet Kalia continue to pursue their sively by ultrasound. Postdoctorate Jason Horng next publications, while Tom Rutkoski, a third- works on polyproline helices and interviews for year student, continues to practice his English academic positions in his native Taiwan. !ird- accent and consider producing his own TV year graduate student Kelly Gorres continues sitcom: “!e Lab.” her research on prolyl 4-hydroxylase after a In the meantime…Ron is working hard to three-month internship at Beckman Coulter keep all of the above functioning as smoothly as in Minnesota. Second-year graduate students possible.

As many of you know, I am “retiring” from the lab to study the detailed biochemistry of various University of Wisconsin during the summer of transposase – DNA contacts. Soheila is just now 2007. I am not dropping out of science (if I did earning her Ph.D. from Michigan State. so, I would drive everyone, particularly Cathy, Big news is that Chris is getting married in crazy), but rather transferring my science to the June and hopes to finish his PhD work by late Marine Biological Laboratory in Woods Hole, summer. Also big news is that Mindy has moved MA. !e whole process is a bit confusing and on to a postdoctoral position at the University of traumatic for me and the other REZ Lab mem- North Carolina and she and Trey are proud par- bers, but nonetheless, we seem to be having a ents of Henry (3/26)! A final bit of news, Archna Bill Reznikoff good time. is leaving Madison for the next step in her career. Lab !e WE in the REZ Lab includes myself, She is joining the Biology Department faculty Igor Goryshin, Deb Hug, Agata Czyz, Chris at Valdosta State University in Georgia. Hmm Adams, and Rich Gradman. We are all work- – maybe we will arrange a lab trip to visit Archie ing on the basic molecular biology of Tn5 trans- next January. Congratulations to Chris, Mindy position. Igor is particularly interested in the and Archie!!! target capture process. Agata is taking off from !is April, the College of Agricultural and where Brandon ended by using small molecule Life Sciences is awarding me the extra mile inhibitors of transposase to define the different award for student advising. Of course it is a big steps in transposition. Chris is studying non- honor for me. However, the truth is that I always specific and specific transposase – DNA com- thought that that was what we were supposed to plexes using single molecule experiments (partly be doing and, in any case, I enjoyed it. in John Marko’s lab in Chicago). Rich is work- Please stop by and visit us but don’t visit ing in two fields – studying the conformational during the summer. I shall be working at the changes needed for synapsis and working with MBL during the summer - actually working Igor on target capture. Starting on April 1, a new at the lab bench. It is great to be at the bench postdoc (Soheila Vaezeslami) will be joining the again!

21 Two New Professorships in Biochemistry by Jim Shurts Laurens Anderson and Henry Lardy !is past year the Department of Bio- the Enzyme Institute from 1950-88. chemistry created two endowed profes- Lardy pioneered work on the preserva- sorships to honor two of our emeritus tion and storage of semen, which has faculty, Laurens Anderson and Henry made artificial insemination in livestock Lardy. We are pleased to be able to pay practical. He is an authority in biochem- tribute to our two distinguished col- istry and is recognized for his research on leagues, and at the same time recognize isolation, purification and characteriza- and support two of our most innovative tion of enzymes involved in carbohydrate current faculty. metabolism. He has more than 370 pub- Funding for the Anderson professor- lications in major journals and books and ship included a generous donation from has received numerous awards, including James Chieh Hsia Mao. Dr Mao, who the Wolf Prize. recently retired after a distinguished career !e initial recipient of the Laurens at Abbott Labs, earned his PhD in biochem- Anderson Professorship in Biochemistry istry under Laurens Anderson in 1963. is Laura Kiessling. Dr. Kiessling earned Laurens Anderson earned his BS her BS from the Massachusetts Institute from the University of Wyoming in 1942. of Technology in 1983, her PhD (1989) He served in WWII with the Army Air in organic chemistry from Yale University Force, then went on to earn the MS and and did postdoctoral work in chemistry PhD in biochemistry at the University at the California Institute of Technol- of Wisconsin. He joined Biochemistry’s ogy. In 1991, she joined the faculty at faculty in 1951, and served until retir- the University of Wisconsin, where she ing in 1986. He was Steenbock Professor is now Professor of Chemistry and Bio- of Biomolecular Structure at Wisconsin chemistry. Her current research emphasis from 1981-86. Anderson’s research on is on biomolecular recognition processes the chemistry, structure, and metabolism and the chemistry and biology of pro- of cyclitols and sugars, and on chemical tein-saccharide interactions. oligosaccharide synthesis, has been pub- !e initial recipient of the Henry lished in more than 90 scientific journal Lardy Professorship in Biochemistry articles. He’s been an active and respected is Ron Raines. Dr. Raines earned his member of the American Chemical Soci- BS from the Massachusetts Institute of ety’s Wisconsin section and its Division Technology in 1980, his MA (1982) and of Carbohydrate Chemistry, and has PhD (1986) in chemistry from Harvard received the ACS Claude S. Hudson University and did postdoctoral work in Award in Carbohydrate Chemistry. biochemistry and biophysics at the Uni- Henry Lardy earned his BS from versity of California San Francisco. In the South Dakota State College in 1939, 1989, he joined the faculty at the Univer- then went on to earn a MS and PhD in sity of Wisconsin, where he is now Profes- biochemistry at the University of Wiscon- sor of Biochemistry and Chemistry. His sin. He joined Biochemistry’s faculty in current research emphasis is on chemical 1945, and served until retiring in 1988. biology, protein design and engineering, He was Professor and Section Chair at and enzymology.

22 Honors & Awards: Faculty: Laura Kiessling – Hilldale Professorship and Harrison Dave Nelson – Alliant Energy Underkofler Excellence in Howe Award Teaching Award

Aseem Ansari – Shaw Scientist Award and Vilas Associates Julie Mitchell – 2006 Sloan Research Membership Award Tom Record – Society Fellow, Biophysical Society Bill Reznikoff – Arthur Maurer Extra Mile Award Mike Sussman – Elected Fellow of the American Associa- Rick Amasino – Howard Hughes Medical Institute Teach- tion for the Advancement of Science; Appointed to WI ing Professors Award; Elected member to the National Biofuels consortium by Gov. Doyle Academy of Science; President-elect of the American Society of Plant Biologists

Postdocs: Graduate Students: Paul D. Boyer Excellence Awards: Graduate Teaching Excellence Award Adrian D. Hegeman Jackie A. Fretz Colon cancer biomarker discovery in the Min muse through stable-isotope assisted This award is intended to recognize a Bio- quantitative proeomics chemistry graduate student who has con- sistently shown evidence of quality, com- mitment, and innovation in teaching. Graduate Mentoring Award Eric S. Underbakke This award acknowledges a graduate student or postdoctoral student who is acknowledged by her/his peers and advisors as This award is designated to honor Bio- one who displays clear promise as a research scientist. Most chemistry graduate students who consis- importantly, the award is to be designated in appreciation of tently provide quality guidance and scien- the student’s consistent willingness to contribute to the intel- tific training in mentoring undergraduate lectual and technical potential of his/her fellow students and students in their research efforts. colleagues through the selfless help of others. Sigrid Leirmo Memorial Award in Biochemistry

Undergraduate Majors: Christian D. Adams Brad A. Hook Mary Shine Peterson Scholarship Recipients: Dejan Acimovic Mia DeFino Yejin Eun Xinhong Lim Rachel Teo Kimberly Clark Scholarship Recipient: Robert Kirchdoerfer Sigma Aldrich Recipient (NEW): This award is to be given to a postdoctoral or graduate stu- Steven Kaul dent who displays clear promise as a research scientist. The Ezra Totten Recipient: award is to be designated in appreciation of the student’s Nicole Jones consistent willingness to contribute to the intellectual and technical potential of his or her fellow students and col- leagues through the selfless help of others. 23 What should Science Education be? by Mike Cox What is science? To those of us trained as sci- is presented as science, then it must actually entists, this is a simple question. Yet, for many, be science. !e wording is straightforward but the answer is unclear. !e different views in our potent. !e bill will provide educators with legal state were made plain in late 2004, when the substance to rely on when they come under pres- school district in Grantsburg, Wisconsin intro- sure from groups who want to introduce pseudo- duced Intelligent Design (ID) into its science science into the curriculum. !e bill will also curriculum as an alternative to Evolution. Dean provide parents interested in good science edu- Michael Zimmerman of UW-Oshkosh and other cation with a cause of action if they need one. deans from across the UW system sent a letter to !e bill has received considerable national Grantsburg, asking that ID be taken out of the attention. It has been endorsed by the Ameri- curriculum. Letters from scientists and educa- can Society for Biochemistry and Molecular tors from around the state soon reinforced the Biology (ASBMB), and is under consideration effort. Our department joined in the summer of for endorsement by the Federation of American 2005, sending a letter that urged the Grantsburg Societies for Experimental Biology (FASEB) and school board to reverse their action, signed by all the Association for the Advancement of Science 35 active members of the department. (AAAS). Interviews with department faculty Members of the Biochemistry faculty wrote describing the bill are widely available on the Letters to the Editor on this issue. !ese trig- internet (Alan Attie has achieved some notoriety gered a response from a sympathetic state leg- by declaring that the bill places Wisconsin in a islator, Terese Berceau. A committee consisting position to be the “un-Kansas”). of Mike Cox, Alan Attie and Rick Amasino of On a related front, the Biochemistry depart- the Biochemistry Department, as well as Elliott ment is adding a new course to its undergraduate Sober, Ron Numbers, Andrew (Anj) Petto (also curriculum. In fall of 2007, the department will Professors in the UW system), and attorney Beth offer its first course directed at non-majors, a course Cox advised Rep. Berceau and helped write a bill in molecular evolution. A movement has also Representative Berceau introduced into the legislature on Feb. 7, 2006. begun to set up a one credit cross-college course, to !e bill, now called the “Science Education Pro- be required for every major generating biological tection Act”, has received considerable national scientists or science teachers, that will introduce attention. In its entirety, it reads: students to the definitions of science, scientists, !e school board shall ensure that any and the scientific method(s). Farther afield, Mike material presented as science within Cox organized a session at the ASBMB meeting in school curriculum complies with all of San Francisco in April 2006 on “Current Topics in the following: (1) !e material is testable Molecular Evolution”, which was complementary as a scientific hypothesis and describes to a session on “Teaching Evolution under !reat only natural processes. (2) !e material of Alternative Views.” is consistent with any description or Want to become involved? We have been definition of science adopted by the impressed with the extraordinary impact elicited National Academy of Sciences. by each action we have taken. Every letter to a !e bill does not ban the discussion of any ideol- school board elicits grateful responses from par- ogy in context. It simply states that if something ents. Letters sent to newspapers get published. Letters sent to legislators are read and responded to. If you are concerned about this issue, write a few letters or get involved in another small way. It need not take a lot of time. Resources are readily available for those interested: Websites of the National Academy of Sciences, the National Center for Science Education and the American Association for the Advancement of Science: http://www.ncseweb.org/, http:// www.nasonline.org/ (search for: evolution sci- ence education), http://www.aaas.org/ (search Faculty stand with Representative Berceau for the introduction of bill 1143 at the Wisconsin State Captiol for: evolution science education). 24 To learn more about the legislation: http://www.legis. To learn what any scientist can do to help the cause state.wi.us/assembly/asm76/news/evolution.html/ of science education (an article on our experiences, published in the Journal of Clinical Investigation): To contact representative Berceau: http://www.legis. http://www.jci.org/cgi/content/full/116/5/1134 state.wi.us/assembly/asm76/asm76.html To view interviews with members of the committee: To contact the department about this issue: http://www.madison.com/archives/read.php?ref=/ [email protected] tct/2006/02/07/0602070356.php, http://www.madison.com/archives/read.php?ref=/ tct/2006/02/16/0602160364.php, http://www.wpr.org (search for, pseudosciences)

Student Faculty Liaison Committee (SFLC) by Mark Meyer Hello from the Student Faculty Liaison Committee! IPiB recruiting for new students. !rough their hard !is year has been an excellent time for advancement work, they have recruited yet another excellent class of of science as the winds of change blow into biochemis- graduate students. try. We saw the changing of the Biochem Chairperson, Every year, the SFLC is proud to bring a student survived a flood, and began the graduate departmental invited speaker to present a seminar and meet with merger of Biochemistry with Biomolecular Chemistry. graduate students. A graduate student representative Here are the highlights from the past year. tallies all nominations and votes from all Biochem- I would like to congratulate our 2005/2006 istry graduate students, and then works very hard in graduate student awards recipients: Christian Adams coordinating that speaker to visit. Last year, Christian and Brad Hook (Sigrid Leirmo Memorial award), Adams brought Dr. Greg Verdine (Harvard University) Eric Underbakke (Graduate Mentoring award), and to speak about the structure and mechanism of DNA Jackie Fretz (Graduate Teaching Excellence award). repair proteins. !is year, Anna Fuzery has invited Dr. !ese awards are designed to recognize graduate stu- Eva Harris (University of California-Berkeley) to speak dents that make a significant contribution to research, in June. Her lab focuses on the Dengue virus. In 1998, teaching, and the department as a whole. !anks to all Eva Harris, along with the other organizers of the students, especially Christian, Brad, Eric and Jackie, Applied Molecular Biology/Appropriate Transfer Tech- in their hard work that continues to make our depart- nology (AMB/ATT) Program founded the Sustain- ment great. able Sciences Institute in order to promote technology As the fresh lot of students arrived in August, our transfer and capacity building in developing countries. social chairpersons, Allyson Anding and Mark Mar- I wish that I could detail all the important con- zinke, made them all feel very comfortable and wel- tributions that every committee and committee come with a great picnic on the Westside of Madison. member makes to the department. Special thanks are Marshall Park was an excellent location, with a large in order for our Student Seminar Series coordinator pavilion, sand volleyball courts, and wonderful views Ryan Marcheshi and all his hard work in organiz- of Downtown Madison over Lake Mendota. !is ing speakers and refreshments throughout the entire social dynamic duo also planned a very festive Holiday year (including the summer!), Alison Albee’s commit- Party, in which many labs participated in an ornament ment to the Departmental Retreat held in May at the contest, displaying the lab PI as well as members. !is Memorial Union, Jared Davis for his organizational year a size and weight restriction was instituted and efforts towards the Egg Drop which we all look for- enforced after the “snow making North Pole monstros- ward to every year, Todd Gruber and Kelly Gorres’ ity” that was entered last year by Sam Butchers lab. work on the graduate and undergraduate (respectively) !anks to all who participated. curriculum for the upcoming students, Samantha With the merging of the programs into the Inte- Herbst in keeping current with the library commit- grated Program in Biochemistry, or IPiB for short, tee, Rachel Britt staying in tune to “Biochem 2009” many challenges arose. !ese challenges were met first building plans, and Steven Darnell for the wonderful by our Recruiting Chairpersons, Bryan Becklund new SFLC website….come and check us out! and Summer Raines. In conjunction with Colleen www.biochem.wisc.edu/SFLC Clary, Flavia Arana, Ellyse Meuer (BMC), and the !anks to all faculty and graduate students that faculty committee, they began the trial and error of have assisted the SFLC over the past year!

25 Faulty Research Spotlight by Cheryl Adams Kadera Vitamin D: The New Old Natural Wonder Drug

Although Vitamin D had long been recognized as an essential nu- tritional factor and key agent for curing the bone diseases rickets and osteomalacia, it was DeLuca who made the crucial discovery that vitamin D’s function requires its conversion, in vivo, into 2 steps to an active hormone, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3, also known as calcitriol). Based on this discovery, he embarked on a comprehensive and brilliantly successful metabolite isolation and characterization program which, within roughly 15 years, resulted in the identification of about 33 vitamin D metabolites. Detailed studies of enzymology, physiology, and endocrinology of this system at the same time elucidated the calcium homeostatic system and especially the vitamin endocrine system. !e culmination of the effort was DeLuca’s beautifully definitive exploration of the regulation of metabolite synthesis, which established 1,25(OH)2D3 as a true hormone, whose synthesis is controlled in typical endocrine fashion by the products of its action (calcium and phosphorus levels) through a feed-back loop involving the parathyroid glands and parathyroid hormone.

!e isolation and characterization of the vitamin D that exhibit unique biologic effects. Over the years, hormone was a keenly pursued and extremely chal- DeLuca’s group has also devoted much effort to the lenging problem at the time (a few micrograms of development and refinement of quantitative assays pure substance were isolated from 1500 chick intes- for the potent vitamin D metabolites used for the tines), and its successful solution ranks as a brilliant diagnosis of bone disorders and for the monitoring technical feat and a true landmark contribution to and management of therapies. steroid chemistry and endocrinology. With his stud- More important than his quite astonishing ies of the regulation of metabolite synthesis, DeLuca output is the intellectual substance of DeLuca’s defined, in biochemical terms, a whole new hormonal work and its impact and consequences. As a result of system and added a major new subject – vitamin D his biochemical work, we now have a much deeper 1996 endocrinology – that since has become a standard understanding of the biological mechanisms con- component of biochemical and medical texts and has trolling normal calcium balance and a much clearer grown into an enormously active field with numerous insight into the causes of several important diseases new investigators from diverse disciplines. With the (e.g., hypo- and hyperparathyroidism, renal osteo- expansion of the field has come the realization that dystrophy, and various types of vitamin D-resistant DeLuca’s vitamin D hormone is a multifunctional rickets). !rough his chemical work and his detailed regulator, whose roles and sites of action include not studies of the biological properties and actions of only the maintenance of calcium homeostasis, but metabolites and analogs, DeLuca played a decisive also the control of cellular differentiation and the role in promoting the development and introduc- modulation of immune responses. !e identifica- tion of the natural hormone and of structural rela- tion of genes responsive to 1,25(OH)2D3, the isola- tives as effective new drugs for the treatment of tion of the vitamin D receptor protein, the cloning, disease. Indeed, the clinical applications of vitamin characterization and regulation of expression of the D compounds are a very significant element and an 1976 receptor gene are but some of DeLuca’s notable con- important consequence of DeLuca’s research. Most tributions. Very fruitful organic chemical syntheses recently, in an outstanding chemical feat, DeLuca are another distinguishing feature of DeLuca’s vita- has synthesized a novel 2 carbon modified 1α,25- min D research program. DeLuca’s team achieved (OH)2D3 analog termed 2-methylene-19-nor- the first chemical synthesis of calcitriol and many (20S)- 1α,25-(OH)2D3 (2MD). !is compound is other natural metabolites; his group also pioneered of particular interest as it has been shown to be effi- the preparation of a variety of systematically modi- cacious in promoting new bone formation. As most fied analogs, thereby resolving basic questions of current drugs utilized for the treatment of osteopo- structure/activity relationships and contributing a rosis decrease bone mineral loss but do not stimulate number of therapeutically efficacious compounds new bone formation, this analog is unique, and is including, for example, 1α-hydroxyvitamin D3, currently under development for the treatment of 1α-hydroxyvitamin D2, the “19-nor” series of ana- postmenopausal osteoporosis. Current or poten- logs and the more recent 2-carbon modified analogs tial medical applications of vitamin D compounds, 1959 26 however, are not limited to calcium metabolism and 1930 – Born in Pueblo, Colorado bone disorders. !e range of possible therapeutic uses 1951 – B.A., Chemistry (Honors), University of Colorado expanded significantly with the demonstration that 1955 – Ph.D., Biochemistry, University of Wisconsin-Madison 1,25-(OH)2D3 promoted the differentiation and 1956-57 – Postdoctorate Fellow, Biochemistry, inhibited the proliferation of malignant cells, and sub- University of Wisconsin-Madison sequent research in many laboratories has confirmed 1958 – Instructor of Biochemistry, that calcitriol, in addition to its well-established action University of Wisconsin-Madison as regulator of calcium homeostasis, also functions as a 1959 – Assistant Professor, Biochemistry, potent stimulator of cellular differentiation for a vari- University of Wisconsin-Madison ety of cell types (e.g., osteoblasts, lymphocytes, kerati- 1962 – Associate Professor, Biochemistry, nocytes, and others). University of Wisconsin-Madison !e preceding concise review illustrates the fundamen- 1965-Present – Harry Steenbock Research Professor, tal substance and numerous important practical exten- Biochemistry, sions of DeLuca’s research. His identification of the University of Wisconsin-Madison biologically active vitamin D metabolites transformed 1970-86 – Chairman, Biochemistry, the long-known vitamin into a multifunctional new University of Wisconsin-Madison hormone and created vitamin D endocrinology as a 1991-05 – Chairman, Biochemistry, new field of knowledge now productively pursued by University of Wisconsin-Madison numerous groups in medicine, physiology, biochem- 1968 – Meade Johnson Award istry, and molecular biology. !e pioneering synthetic of !e American Institute of Nutrition work initiated by his team has led to a great resur- 1969 – Andre Lichtwitz Prize from the French Institut gence of interest in steroid and vitamin D chemistry National de la Sante et de la Recherche Medicale and that subject now engages the attention of at least 1973 – Osborne and Mendel Award a dozen academic laboratories and a roughly equal of !e American Institute of Nutrition number of pharmaceutical companies. !e combined 1974 – Honorary Degree Doctor of Science, efforts of these groups have yielded some elegant new University of Colorado-Boulder synthetic routes to vitamin D compounds, and they 1974 – Roussel Prize of France have generated a very large collection of structural 1974 – Gairdner Foundation Award (Canada) analogs exhibiting a broad range of medically useful 1978 – Membership in the American Academy activity patterns. Some of these compounds already of Arts & Sciences have found important application for the treatment 1979 – Membership in the National Academy of Sciences of human disease, and current intensive development 1980 – Honorary Degree Doctor of Science, efforts will undoubtedly yield further additions to the Medical College of Wisconsin, Milwaukee present list of therapeutically useful agents. Professor 1983 – 3M Life Sciences Award of the Federation DeLuca’s vitamin D research, in short, represents out- of American Societies for Experimental Biology standing basic medical science with highly beneficial 1983 – Bristol-Myers Squibb/Mead Johnson Award practical consequences. for Distinguished Achievement in Nutrition Research Professor DeLuca has also been active in the 1985 – Honorary Degree Doctor of Medicine, creation of new commercial enterprises. He played Karolinska Institute, Stockholm, Sweden a major role in the start-up of Tetrionics, Inc. (now 1987 – Spencer Award, American Chemical Society, Sigma Aldrich Fine Chemicals), Bone Care Interna- Kansas City Section tional (now Genzyme), QuantiGel, and most recently, 2002 – Elected Fellow of the his own company, Deltanoid Pharmaceuticals, Inc. Wisconsin Academy of Sciences, Arts, and Letters For these efforts, he was recently recognized as Ernst Granted over 500 U.S. patents & Young Entrepreneur of the Year (2004) for the State and 150 active foreign equivalents of Wisconsin. Over 1100 publications in the following fields: In conclusion, Dr. DeLuca’s entire career has been Vitamin A, Vitamin D, Parathyroid hormones and Calcitonin devoted to scientific discovery, invention, and develop- ing his ideas into medications that have improved the inventor in the history of the Wisconsin Alumni Research Founda- health and wellness of people all over the world. He tion (WARF), resulting in more revenues than all other inventors also demonstrated innovation and success in leading combined. the Biochemistry Department to its current rank as Following is a link to the talk given by Dr. DeLuca at the Over- one of the top biochemistry departments in the world. ture Center in downtown Madison on March 7, 2006: http://www. Added to this is the fact that he is the most prolific researchchannel.org/prog/displayevent.asp?rid=3456 27 Postdoctoral Fellowships: Name Lab Fellowship Allen, Matthew J. Raines/Kiessling NIH - NRSA Postdoctoral Fellow Allingham, John S. Rayment Canadian Postdoctoral Fellow Byrd, Dana T. Kimble NIH – NRSA Postdoctoral Fellow Clee, Susanne M. Attie American Heart Postdoctoral Fellow D’Silva, Patrick R. Craig American Heart Postdoctoral Fellow Higurashi, Takashi Craig Human Frontiers Science PD Fellow Hollenbeck, Jessica Kiessling NIH – NRSA Postdoctoral Fellow Kotch, Frank W. Raines NIH – NRSA Postdoctoral Fellow Lam, Ngan Kimble Damon Runyon Postdoctoral Fellow Lee, MyonHee Kimble Howard Hughes Postdoctoral Fellow Nykamp, Keith R. Kimble Howard Hughes Postdoctoral Fellow Phillips, Bryan T. Kimble NIH – NRSA Postdoctoral Fellow Pierce, Brad S. Fox NIH – NRSA Postdoctoral Fellow Sobrado, Pablo Fox American Heart Postdoctoral Fellow Wang, Tao Craig American Heart Postdoctoral Fellow Xia, Xiaofeng Martin American Heart Postdoctoral Fellow Zhao, Enpeng Attie American Diabetes Postdoctoral Fellow Graduate Student Fellowships University: Name Lab Fellowship Nicholas Reiter Butcher CALS Wisconsin Distinguished Fellow Katie Williams DeLuca R.H. Burris Fellow Kara Lynch Martin AHA Predoctoral Fellow Harini Sampath Ntambi AHA Predoctoral Fellow Brian !omson Clagett-Dame AHA Predoctoral Fellow Melissa Davis Holden NSF Fellow John May Kiessling NSF Fellow Graduate Student Fellowships Departmental: Name Lab Fellowship Sungtae Kim Pike Babcock Fellow Jack Borrok Kiessling Biochemistry Scholar Caroline Davis Record Biochemistry Scholar Jae Eun Kwak Wickens Mary Shine Peterson Fellow Julia Cox Cox Peterson Fellow Karl Hauschild Ansari Peterson Fellow Christopher Warren Ansari Peterson Fellow Allison Albee Wiese Steenbock Fellow Julia Drees Cox Steenbock Fellow Dipali Sashital Butcher Wharton Fellow

28 Biochemistry Degree Listing 2005/2006 Degree Name (Major Professor) Thesis Title

PhD Binkowski, Brock F I. Ligand Regulated Peptides: A general approach for using small molecules to (Belshaw) regulate the interaction of intracellular peptides with target proteins II. Novel Strategies for Error Correction on Gene Synthesis Products

PhD Flowers, Matthew, T The Role of ABCA1 and SCD1 in Lipoprotein and Cholesterol Metabolism (Attie)

PhD Kersteen, Elizabeth, A Protein Folding Enzymes: Protein Disulfide Isomerase and Prolyl 4-Hydroxylase (Raines)

PhD Hinkley Glen, T Ligand Effects on the Reduction Potential of the [4Fe-4S] Cluster in Lysine 2,3- (Reed) Aminomutase

PhD Levitsky, Konstantin Selective Modulation of Receptor Activity by Proximity-Accelerated Alkylation (Belshaw)

PhD Pottekat, Anita Molecular cell biology of GlcNAc-PI de-N-acetylase (PIG-L), the second enzyme (Menon) of the GPI biosynthetic pathway

PhD Sims, Paul, A Mechanistic and Function Studies of Enolase: an Investigation of the Structure (Reed) Relationships Among Variant Enolases and the Corresponding Active-Site Resi- dues of the Wild-Type Ennzyme

PhD Bae, Euiyoung Structure, Function and Dynamics of Psychrophilic, Mesophilic and Thermo- (Phillips) philic Adenylate Kinases

PhD Moe, Luke, A Mechanistic and Structural Studies of the Toluene 4-Monooxygenase from Pseu- (Fox) domonas mendocina KR1

MS Owen, Heather, J Characterization of Mengovirus 3BCD Proteins in the Nucleus (Palmenberg)

MS Simon, Brook, P Yeast PUF6 protein (Wickens)

MS Buter, Natascha The novel mammalian poly(A) polymerase, GLD-2 (Wickens)

MS Turbeville, Christopher, A Far-Red Light, Gibberellins, and the Transition to Flowering (Amasino)

MS Liu, Yong Heavy atom isotope effects on the reactions catalyzed by the mutants of oxalate (Cleland) decarboxylase from Bacillus subtilis and oxalate oxidase from barley roots

29 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 for us, please call or write to the indi- Sebastian Bednarek...... [email protected]. . . . 608/263-0309 viduals listed below. Sam Butcher ...... [email protected] . . . . . 608/263-3890 Margaret Clagett-Dame . [email protected]...... 608/262-3450 University of Wisconsin-Madison, Mo Cleland ...... [email protected] . . . . . 608/262-1373 Department of Biochemistry Mike Cox ...... [email protected] ...... 608/262-1181 433 Babcock Drive Betty Craig ...... [email protected] ...... 608/263-7105 Madison, WI 53706-1544 Hector DeLuca ...... [email protected] ...... 608/262-1620 Brian Fox ...... [email protected] ...... 608/262-9708 FAX # (608) 262-3453 Perry Frey ...... [email protected] ...... 608/262-0055 Paul Friesen ...... [email protected] ...... 608/262-7774 Change of Address, Information, Colleen Hayes ...... [email protected]...... 608/263-6387 and General Inquiries: Hazel Holden ...... [email protected] 608/262-4988 Ross Inman ...... [email protected] ...... 608/262-9881 Cheryl Adams Kadera Laura Kiessling ...... [email protected]...... 608/262-0541 (608) 262-9835 Judith Kimble ...... [email protected] ...... 608/262-6188 E-mail: [email protected] John Markley ...... [email protected] . . . . . 608/263-9349 Tom Martin ...... [email protected] ...... 608/263-2427 Graduate Studies Julie Mitchell ...... [email protected]...... 608/263-6819 (Information and Applications): Rebecca Montgomery .... [email protected] ...... 608/262-6773 Dave Nelson...... [email protected]...... 608/263-6879 Colleen Clary (608) 262-3899 James Ntambi ...... [email protected] . . . . . 608/265-3700 E-mail: [email protected] Ann Palmenberg ...... [email protected]...... 608/262-7519 George Phillips ...... [email protected] . . . . . 608/263-6142 Undergraduate Program/Internships Wes Pike ...... [email protected] ...... 608/262-8229 Ron Raines ...... [email protected] ...... 608/262-8588 Dan Barnish (608) 265-9846 Ivan Rayment ...... [email protected] 608/262-0437 E-mail: [email protected] Tom Record ...... [email protected] ...... 608/262-5332 George Reed...... [email protected] ...... 608/262-0509 Steenbock Symposia Bill Reznikoff ...... [email protected] . . . . 608/262-3608 Mike Sussman ...... [email protected] . . . . 608/262-8608 Janice Carberry (608) 262-7129 Marvin Wickens ...... [email protected]. . . . . 608/262-8007 E-mail: [email protected] Chris Wiese ...... [email protected]...... 608/263-7608 Emeritus Gifts/Donations Julius Adler ...... [email protected] ...... 608/262-3693 Please use the form at the right Laurens Anderson ...... [email protected] ...... 608/262-3041 or go online to: Helmut Beinert ...... [email protected] ...... 608/263-6357 www.uwfoundation.wisc.edu Robert Burris ...... [email protected] ...... 608/262-3042 You may also contact the Chair: Jack Gorski ...... [email protected] ...... 608/263-4441 Betty Craig Alfred E. Harper ...... [email protected] (608) 262-3040 Paul J. Kaesberg ...... 608/262-2205 E-mail: [email protected] Henry Lardy ...... [email protected]...... 608/262-3372 Roland R. Rueckert ...... [email protected]...... 608/262-6949 Heinrich K. Schnoes ...... 608/262-0650 John W. Suttie ...... [email protected]...... 608/262-2247

30 Donors to Biochemistry Funds in 2005 Julius and Hildegard J. Adler Carl W. Gilbert Hipolito V. Nino Alexander Capital Kurt A. A. and Sandra K. Grunwald Linda J. O'Gara American Chemical Society Glen E. Gutzke Mary S. Ozers Janet S. Arnold Kenneth E., Jr. and Janet H. Hamlin Erik A. Petrovskis Walter M. Barker Mark C. Harbeck George N. Phillips, Jr. Karl M. Beck Robert P. Hausinger and John G. Primm Wendy A. Bedale Susan L. Kalvonjian Promega Corporation Raymond E. and June F. Benenson Herbert R. Heinicke William S. Reznikoff Duane A. and Norma M. Benton Mark A. Hermodson Quinton R. Rogers Maryka H. Bhattacharyya Jeffrey P. Houchins Alice V. Rohde Charles E. Biddlecome !omas D. Huggett Michael C. and Julia B. Roskos Anne L. Bosch William T. and Lynn Jackson !omas J. Ryan James T. Bradley Diane Keller Arthur G. Saponara William E. and Lily M. C. Brown John H., Jr. and Luella B. Keyes Saul A. Schepartz Jeffrey L. Browning Kimberly-Clark Corporation Richard U. and Elizabeth G. Schock Bruker AXS Inc. !ora M. Kinseth Charles F. and Cynthia J. Shuler Bruker Biospin Corporation Donald A. Kita James D. Shull George E. Bunce Kevin J. Kleinfeld Margaret Shupnik Gregory M. Campbell William E. and Anita J. Koerner Donald J. and Ann R. Siehr Carolyn A. Campen Martin F. Kovacs, Jr. David P., Jr. and Barbara L. W. Silva Douglas B. Chapman Henry A. and Annrita Lardy !omas J. Skatrud Ranjini Chatterjee Margaret I. Leonard Donald E. Slagel Warren J. Close William L. Leoschke Frederick G. Smith Gladys M. Dahl Jennifer M. Loeb Kevin M. Sokolowski Arnold E. and Catherine M. Denton Hope Lowry Pari D. N. Spolter DNASTAR Inc. Frank Maley Robert E. Stutz Edward M. and Susan Z. Domanico James C. Mao Nancy Torbet Donn R. Dresselhuys John L. Markley James J. Vavra Lawrence B. Dumas, Jr. Morris Mauer Brian F. Volkman Epicentre Technologies Corp. John P. Mc Cutcheon Douglas E. Vollrath Financial Management Inc. Helen W. Mc Intire Robert S. Wehbie Roy H. Fishman Wayne F. Mc Intire William W. Wells Brian G. Fox Kenneth S. Meyer Steve R. West and Julie A. Waterbury Vincenzo Franco and Barbara Gerratana Jennifer A. Miskowski Joseph and Janet C. Wiltzius Frederick G. Freitag and Lynn N. Stegner John E. Morris Michael G. Wittekind Jennifer Garvin-Cress Marcia L. Moss Ming-Chi M. Wu Jason E. Gestwicki Alvin L. Moxon Maija V. Zile

31 Department of Biochemistry University of Wisconsin–Madison 433 Babcock Drive Madison, WI 53706-1544 USA FIRST CLASS

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