For Friends of the Department of Biochemistry at the University of Wisconsin–Madison Table of Contents from the Chair

Home , Har Gobind Khorana, JoAnne Stubbe, John Gurdon, Judith Klinman, Madison Radicals

For friends of the Department of Biochemistry at the University of Wisconsin–Madison Table of Contents From the Chair...... 3 Biochemistry Advisor Graduate Degrees ...... 28 Exciting Discoveries ...... 4 Education and Training...... New Tripartite Biochemistry Complex ...... 9 Postdoc Program...... 30 Profiles...... Graduate Program: IPiB...... 31 Jill Wildonger...... 10 Graduate Student Organization: SFLC...... 32 Aaron Hoskins...... 11 Undergrad Program: UBSO...... 33 Scott Lowe...... 13 In Memoriam...... Lars Renner...... 14 Paul Kaesberg...... 34 Dave Nelson...... 15 Mo Cleland...... 35 Hector DeLuca...... 16 Masayasu Nomura...... 36 Lardy, Burris, Potter: South Dakota's Gifts...... 17 Chris Raetz...... 37 International Programs...... 19 Gobind Khorana...... 38 Our Department in India...... 20 Honors and Awards...... 40 Our Department in England...... 21 GLBRC...... 44 Our Department in Uganda...... 22 From the Labs ...... Pre-pre PhD programs...... Emeritus...... 45 Project CRYSTAL...... 24 Current...... 48 Micro Explorers...... 25 Contact Information ...... 66 Biochemistry Graduate Degrees ...... 26 Donors ...... 67

"Elmer" nestled amongst the Biochemistry buildings Photo courtesy of Hedrich Blessing From the Chair By Professor Betty Craig

the “Henry A. Lardy Undergraduate As his passing occurred so close to our Research Fund” and the “Karen M. print deadline, you will find only a Telander Undergraduate Research short mention in the pages that follow. Fund.” Henry Lardy, as you all know, Our next newsletter will provide a full was a giant of our department. He memorial. A symposium in honor and passed away in 2010 – you may celebration of his lasting contributions recall a tribute to his enduring to mechanistic enzymology is planned example in that year’s newsletter. for May 22-24, 2014 here in Madison. Karen Telander was an undergrad at We hope to see many of you there. UW-Madison who went on to pursue Check our website for updates and It’s been a while since last we wrote, a career in research, research ethics, and an opportunity to contribute to his but I think you’ll find us worth the wait. undergraduate education. She passed legacy (http://www.biochem.wisc. Marv Wickens and colleagues have away in 2009 – her husband initiated edu/news/default.aspx?id=252) pieced together a mosaic here that I hope a scholarship in her honor to support gives you a glimpse of the excitement and women and minority undergrads In the past few years, we’ve had three energy of the department’s goings on. in chemistry and biochemistry. retirements from and two additions to our faculty. I’m pleased to say that while Among my favorites are the I’m pleased to report that as we go George Reed, Dave Nelson, and Hector increasing opportunities we’ve been able to press in spring 2013, the building DeLuca have all retired, we are lucky to offer our undergrads to experience and renovation so omnipresent in to continue to see them frequently the wider world. Our faculty has worked recent newsletters is done. Almost. around the department, and Hector’s tirelessly to develop unique study The new research tower (also known as lab is still going strong (page 16). abroad experiences that enhance our the “Biochemical Sciences Building”) We’re also pleased to have welcomed students’ international perspective and was occupied in January of 2012. The Aaron Hoskins and Jill Willdonger to understanding of science. Aseem Ansari’s final step, complete renovation of the department in 2011. Both came Khorana Program (page 20), James floors 4 – 6 of the “85 wing,” will be to us with prestigious NIH Pathway Ntambi’s Uganda Program (page 22), completed in July of this year. See page to Independence Awards that have and Marv Wickens’ SCORE (England) 9 for a more complete description of helped them hit the ground running. Program (page 21) take students the tripartite complex as documented They introduce themselves and their into labs and lives across the globe. by Mike Cox, the “architect in roads to Madison on pages 10 – 12. charge” of this massive project. We’ve also established a summer I hope you enjoy what you read research program for undergrads in Sadly, we share a long “in and see in this issue – the new, more our labs here at home. The program memoriam" section to offer tribute colorful look of our newsletter. May provides students both the opportunity to colleagues we have lost since you it bring back pleasant memories of to experience full-time research and received our last newsletter – Paul your time in Madison in general, the financial assistance necessary to Kaesberg, Chris Raetz, Har Gobind and the department in particular. do so, making the important research Khorana, and Masayasu Nomura. Mo experience accessible to all. Our two Cleland, too, died tragically on March Remember, we are always happy to newest scholarships are supported by 6th this year following a fall on ice. hear from you, and visit us when you can.

E-mail: [email protected] Regular mail in care of the department – see page 66 for address information NEW: Like the Department on Facebook facebook.com/UWMadisonIPiB

3 New Discoveries A sampling of the Department's pioneering research in areas ranging from metabolism to gene regulation to enzymology.....

A new regulator of insulin. The Attie lab positionally cloned a gene for Type 2 diabetes, Stxbp5L, which encodes an inhibitor of insulin secretion called tomosyn-2. The work shows that beta-cells produce an inhibitor of insulin secretion and so have to inactivate this inhibitor to secrete insulin.

Sushant Bhatnagar & Alan Attie

Structures of splicing complexes. Butcher's group determined the structures of U6 spliceosomal RNA in complex with its protein and RNA binding partners using NMR, x-ray crystallography and small angle x-ray scattering. These structures reveal how the essential Prp24 protein interacts with U6 RNA to mediate the structural rearrangements required for spliceosome assembly. Additionally, we determined the structure of the U2/U6 RNA complex, providing the first view of this important component of the spliceosomal catalytic core.

Jordan Burke & Sam Butcher

New Activity of Pyruvate Carboxylase. The Cleland lab discovered that oxamate, an analog of pyruvate, is a substrate for pyruvate carboxylase, being converted to a carbamate analog of oxaloacetate. The carbamate is very acid-labile, which is why it was not discovered earlier. The study made use of C-13 NMR to detect the carbamate.

Mark Anderson, Laurie Reinhardt, Mo Cleland & Tonya Zeczycki

Controlling Fe-S cluster biogenesis. A post-translational mechanism regulating the cellular level of the scaffold protein on which Fe-S clusters are built was uncovered in the Craig lab. Degradation by the mitochondrial Lon protease modulates the scaffold’s stability over a 10-fold range, allowing cells to rapidly adapt their Fe-S cluster assembly and repair capacity to changing environmental conditions.

Ji-Yoon Song & Betty Craig 4 Natural symbiosis in carbon cycling. The Fox and Currie labs showed that pine-boring woodwasps inoculate the trees with a bacterium that enhances the destructive nature of the insect attack, thus providing a new example of symbiotic contributions to carbon cycling in terrestrial ecosystems. The potent mixture of enzymes secreted by the bacterium also gives insight into new approaches for enzymatic deconstruction of cellulosic biomass for industrial purposes such as biofuels production.

Amy Lim, Brian Fox, Shishir Chundawat, Johnnie Walker, Lai Bergeman, Kirk Vander Meulen, Chris Bianchetti & Taichi Takasuka

A new viral strategy. Baculoviruses use a novel mechanism to modulate the host DNA damage response during infection, as shown in the Friesen group. While baculoviruses need the host's DNA damage response machinery for their own viral DNA replication, they also encode a novel protein to modify the response to transform it from an antiviral pathway to one that expedites DNA virus multiplication.

Paul Friesen, Jonathan Mitchell & Nathaniel Byers

New mechanism of translational control. A new mechanism for translational control, conserved from nematodes to humans, has been uncovered in the Kimble lab. This mechanism brings together a core component of the translational elongation machinery with an Argonaute protein and a PUF RNA- binding protein to arrest ribosomes on selected mRNAs near the site where the nascent polypeptide chain emerges from the ribosomal exit tunnel.

Kyle Friend & Judith Kimble

Protein dynamics and Fe-S clusters. Iron-sulfur clusters are ubiquitous and their mis-assembly can cause disease. The Markley group discovered that the scaffold protein for iron-sulfur cluster assembly and delivery (IscU) is metamorphic. This ancient and highly-conserved protein populates two conformations: one is more structured, and the other, more dynamic (D). The two states differ by the configurations of two peptidyl-prolyl peptide bonds. Both forms of the protein are physiologically important, performing different roles in the cycle of iron-sulfur cluster assembly and delivery.

Jin Hae Kim, John Markley & Ziqi Dai 5 New Discoveries continued

Proteins that drive membrane fusion. Vesicle-plasma membrane fusion is responsible for the secretion of inflammatory mediators from mast cells. The Martin group found that Munc13-4, which plays a key role in mast cell degranulation, is able to stimulate liposome fusion in a Ca2+- and SNARE-dependent manner. This work reveals general principles by which priming/tethering factors operate to drive membrane fusion, and will contribute to understanding genetic diseases involving Munc13-4 mutations.

Declan James, Joe Esquibel & Tom Martin Not pictured Kristin Boswell & Steve Bruinsma

Perfecting computational predictions. Computational prediction of binding mutagenesis effects is a major challenge. The Mitchell lab developed models that accurately identify mutations that disrupt protein-protein binding and allosteric communication. In three CAPRI international blind prediction experiments, the lab returned top results in predicting the effects of 19 substitutions/residue on protein- protein binding; in identifying de novo designed interfaces that form stable complexes; and in docking heparin to a hypothetical protein of uncharacterized function.

Steve Darnell, Spencer Ericksen & Omar Demerdash Not pictured Xiaolei Zhu & Julie Mitchell

Surprises in your skin. The Ntambi group has discovered an entirely unexpected role for skin monounsaturated fatty acids in the regulation of energy expenditure and the development of obesity. They have found that Stearoyl-CoA desaturase-1 is a key enzyme in the skin, and its expression controls energy expenditure, hyperphagia and protection against high fat induced obesity and insulin resistance.

Harini Sampath, Matt Flowers, Makoto Miyazaki & James Ntambi

Controlling mitochondria. Mitochondria are centers of metabolism and signaling whose content and function must adapt to changing cellular environments. By combing genomics and proteomics technologies with classic biochemistry and cell biology approaches, the Pagliarini group has shown that cells use a variety of post-transcriptional and post-translational regulatory mechanisms to adapt to acute and chronic physiological stresses, including fasting, obesity and iron deprivation.

Jarred Rensvold, Joshua Carson, Paul Grimsrud, & Dave Pagliarini

6 Relatives of the common cold virus. More than 150 “types” of human rhinoviruses have been isolated. The fundamental question of why not all of them cause the same disease, i.e. the common cold, has now been answered in the Palmenberg lab. A protease called “2A” encoded within each genome shows extensive sequence diversity and consequent mechanistic selectivity for cellular substrates to account for differential pathogenic responses when these viruses infect. Three species of rhinoviruses actually recombine among each other to swap this genome segment providing almost unlimited variation in disease-causing capacity.

Woonghee Lee & Ann Palmenberg

From crude biomass to sugars. The Raines group has shown that an ionic liquid containing water and catalytic acid can be used to capture nearly all of the latent sugar within any crude biomass. The recovered sugar supports the vigorous growth of bacteria and yeast. This simple process is the basis for an award-winning start-up company: Hyrax Energy, Inc.

Ron Raines & Joe Binder

A new natural plant homopolymer. Yuki Tobimatsu in the Ralph lab, working with collaborators at the Noble Foundation (Ardmore, OK), discovered a ‘new’ natural polymer derived from chemical radical coupling of caffeyl alcohol, the ‘missing monolignol.’ Vanilla bean seed coats are composed of 80% of this new lignin polymer and 20% polysaccharides. (PNAS cover article, and Science highlight)

John Ralph & Yuki Tobimatsu

Dissecting Transcription Initiation. The steps and intermediates in transcription initiation by E. coli RNAP have been analyzed in the Record lab. After initial sequence-specific binding, a series of large- scale conformational changes bends the start site region of the promoter into the enzyme’s active site cleft. Then, base flipping nucleates opening 13 bp in the cleft. This initial unstable open complex is stabilized by rearrangement of the non-template strand and step-wise assembly of mobile elements of RNAP on the “downstream” duplex, increasing its lifetime by a factor of 105. We now can determine how initiation is controlled by promoter sequence, protein factors, and solution variables.

Jan Murray, Raashi Sreenivasan, Emily Ruff, Mike Capp & Tom Record. Recent alum researchers in my lab responsible for many of our recent discoveries include Amanda Drennan, Sara Heitkamp, Ruth Saecker, Ted Gries, Wayne Kontur & Carrie Davis. 7 New Discoveries continued

The first structural analysis of a membrane protein in the bacterial division complex.A sophisticated protein machine -- the divisome -- ensures that bacterial cells divide and the right time and place. The Senes group determined the structural organization of FtsB, an essential protein in that complex, using biophyiscal and computational methods and X-ray crystallography collaboration with Keenan Taylor and Ivan Rayment). Their work defines the structure of its membrane and periplasmic domains, and reveals that FtsB self-associates. Association with another protein (FtsL) appears to stabilize the periplasmic domain of FtsB, which in turn is critical for recruitment of other proteins to the division complex.

Loren LaPointe, Keenan Taylor (Rayment lab) and Alessandro Senes

Discovering the basis of membrane asymmetries. The Weibel group has shown that strain on membranes alters the local composition of intrinsically curved, anionic phospholipids. It thereby influences the positioning and function of amphipathic proteins in bacteria.

Lars Renner & Doug Weibel

mRNA regulation by design. TheWickens lab has used the scaffold of the PUF protein family to create proteins with new specificities. The lab’s new selection and deep sequencing methods, termed SEQRS, enable the global specificities of these proteins to be determined. Designed “neo-PUF” can turn up or down the expression of specific mRNAs in early development.

Marv Wickens, Zak Campbell, Amy Cooke & Andrew Prigge

8 The New Tripartite Biochemistry Complex A major new building and imaginative renovation provide striking and flexible space. By Professor Mike Cox

Those of you who have not visited the department in a few years are in for a surprise – a major expansion and redesign of our buildings. The new “Biochemistry Complex” consists of three buildings linked by walkways (see the drawing lower right), and is nearly complete and occupied. The 1912 and 1937 wings remain but have been highly renovated for teaching, while an entirely new building View from Henry Mall has been constructed that is dedicated clockwise from left 1912 and 1937 buildings,1998 addition (center), 2012 BSB, to research. The third building is the 1906 former Ag Journalism building. Photo courtesy FLAD Architects. “Biochemistry Addition,” which has been The new research tower and The 1998 Biochemistry Addition around since 1998, and houses most of “Biochemical Sciences Building” The third building in the complex is the our faculty. An entirely new building dedicated 1998 Biochemistry Addition, and is now Let me walk you through what we to research has replaced the 1956 wing. surprisingly the oldest part of the complex! have done: This new structure (plus the 1906 Ag It currently houses and supports the work Journalism building and the 1985 of 21 Biochemistry faculty and 3 Emeritus The new old “Biochemistry Building” Biochemistry tower) are all interconnected Biochemistry faculty. From the outside, the façades of the 1912 and constitute the Biochemical Sciences It is an impressive complex, integrating and 1937 buildings on Henry Mall and Building. The new labs house the research with teaching, and providing a University Avenue are the same. The new, Biomolecular Chemistry department on flexible and diverse collection of wonderful large building – called the “Biochemistry floors 4-5-6, and Biochemistry faculty spaces. And it awaits your visit! Building” – has our old 420 Henry Mall on floors 2 and 3. The 1906 part of the address. Inside, the building has been building houses some new computational completely renovated and redesigned spaces, a faculty meeting room, office for teaching functions. But there’s much suites, and a coffeehouse! The Biochemical more here than a few new classrooms and Sciences building is connected to the teaching labs – though those are present, other two by enclosed skybridges. and radically and beautifully improved. We have added many new functions: a highly computerized classroom to instruct students in the use of modern databases and bioinformatics; a new undergraduate lounge, providing a space for students to wait for classes and study; numerous new meeting rooms; entirely new spaces dedicated to computation. The infamous congestion outside the hallway of our old Room 125, before and after class, is a thing of the past! The Curry Murals, which I am sure many of you remember, were carefully protected during construction, and professionally cleaned and restored afterwards.

Right: Aerial view of the Biochemistry complex. Photo by Joe Oliva.

9 New Faculty Profiles Our two newest faculty, Jill Wildonger and Aaron Hoskins, recount their scientific histories and how they came to join us. Professor Jill Wildonger Cells are not from the retinal explant in all directions, and those interactions opened my eyes circles. We may making it look like a many-rayed star. to how research blossoms when people often see them How did these neurons “know” when to with different expertise join forces. drawn that way, sprout an axon, how did the axons grow, This early experience of reaching out to but their shapes and what molecules made it all happen? other groups to learn new techniques and structures My undergraduate research experiences continues to inspire me to connect with are incredibly were varied, and took me from zucchini other groups and work collaboratively. diverse. Nowhere to chickens and bullfrogs, using methods Even the simplest nervous system is the pairing and from biochemistry, cell biology and is comprised of hundreds of neurons: complexity of form and function more electrophysiology. But as I edged toward a nematode worm no larger than a on display than in the nervous system. graduation, I found myself reading more comma on this page has approximately Neurons are frequently described as tree- and more papers on neuronal development 300 neurons, fruit flies have 100,000, like, having a single axonal “trunk” and an and nervous system assembly – the and human beings have a staggering 85 “arbor” of dendritic branches. Extending beginning of a girl-meets-brain love story. billion nerve cells that form over a trillion this analogy, we can think of our brains When I started the graduate program synaptic connections. Yet virtually all as small “forests” of neurons, which in Neurobiology and Behavior at nerve cells, from worms to flies to humans, pass messages to each other via these Columbia University, I felt certain that share basic structural features: neurons trunks and branches. I want to know I would study neuro-development. Yet I have dendrites that receive signals and how cells generate these very different was drawn to join a lab in the Department axons that transmit them. Defects in axon shapes, and tailor them for specialized of Biochemistry and Molecular and/or dendrite morphogenesis underlie functions – a molecular understanding Biophysics headed by Dr. Richard Mann, many human diseases; nonetheless, I was of how cell shape and activity arise, whose main research interests include surprised to find that still very little is and are linked to one another. Hox protein function and patterning, known about the molecular mechanisms Everyone remembers the first using fruit flies as a model system. “Do responsible. So I headed off to San time they fell in love. I was a college fruit flies even have a brain?” one of my Francisco to join the lab of Dr. Yuh sophomore, and the lightning bolt struck classmates teased. Yet in the next few Nung Jan, whose group had recently while I looked down the eyepiece of a years, I studied how development of the developed genetic tools to illuminate microscope. I had seen drawings and nervous system is shaped by neuronal individual neurons in live intact animals, photos of cells, but seeing the neurons of a specification and programmed cell death, opening up new approaches to investigate developing chick retina cultured in a dish blending genetics, molecular biology, neuronal morphogenesis. A forward was something else. I was mesmerized. microscopy and biochemistry. We genetic screen utilizing these tools The delicate axonal processes grew out frequently collaborated with other labs, uncovered a critical role for the molecular

The cellular complexity of sensory neurons illuminated in a live, developing fruit fly (photo far left). We can track how ion channels are transported within neurons by adding fluorescent tags (see photos on the right). This particular ion channel belongs to a superfamily whose members are activated in response to salt as well as mechanical stimulation and pain.

10 motor dynein in polarized dendritic contributions to a range of scientific localization in neurons in vivo to isolating transport and maintaining axonal fields. From the very first, members motor proteins for in vitro biochemical identity. While dynein has a well-known of biochemistry, neuroscience, fruit assays to developing new genome role in “walking” along the microtubule fly, and developmental biology groups engineering techniques; the latter project cytoskeleton in cells, our research on campus have given my lab a warm I am happy to say is in collaboration with revealed an unexpected role for dynein welcome, including us in group meetings the Cox, O’Connor-Giles and Harrison in organizing microtubules within axons. and suggesting collaborative projects. labs. We are actively recruiting graduate These studies sparked my continuing Looking back over the past year since the students, and look forward to welcoming interest in how molecular motor proteins lab started, it’s exciting to see how we’ve a post-doctoral fellow in the spring. work in concert with microtubules to grown as a lab, and how projects that A friend from graduate school recently build neuronal structure and function. were simply ideas on paper last January asked me whether I was happy in my Since one of my favorite aspects of have come to life (in some cases, quite new position, and jokingly asked, “Do being a researcher is interacting with literally, since we’ve been generating you skip, dance and sing to lab every other people who are passionate about transgenic fruit fly strains). Our very day?” I said I usually bike, although science, I’m thrilled to be a part of the talented and enthusiastic lab manager was there was a pretty big grin on my face. scientific community at Madison. I’m joined this fall by several undergraduate It’s been an amazing year, and I am very also inspired (and frequently awed) to students, and we are currently tackling excited about what the next ones will bring. be the colleague of researchers who have projects ranging from the live imaging of made and continue to make important motor protein dynamics and ion channel

Professor Aaron Hoskins Since starting synthesizing novel molecules, designing highly processive, purified enzymes. The my laboratory at complex kinetic experiments, or spliceosome, on the other hand, could UW in August developing new spectroscopic techniques not be purified, is composed of dozens 2011, one of the if current methods or molecules were of components, and is a single turnover highlights has been insufficient. Learning how to step outside enzyme. The key to single spliceosome how much I enjoy my comfort zone and focus on the experiments turned out to be the talking about experiments that will answer questions, combination of yeast genetics, chemical biochemistry not just experiments that my labmates or I tools, and a fluorescence technique with the UW knew how to do, has had a lasting impact called CoSMoS (Colocalization Single undergraduates. They nearly always ask on my career. Key to this was a thorough Molecule Spectroscopy). Together, this me some variation of “Why did you and broad training in biochemistry combination allowed me to probe reaction decide to become a biochemist?” It is that has since proven invaluable. reversibility, kinetics, ordering, and slightly bewildering to be on the other After my PhD work, I decided to even conformational changes that were side of that question. It seems like I was an visit the RNA World. Melissa Moore and occurring during the splicing reaction. undergraduate at another Big Ten school Jeff Gelles (UMass Medical School and Single molecule biochemistry greatly pondering my future just a few years ago! Brandeis U., respectively) proposed that I appeals to the “making stuff” and Looking back, I became a biochemist use single molecule fluorescence methods “measuring stuff” aspects of my because I like to “make stuff” and “measure to study the spliceosome: a eukaryotic personality. The microscopes my stuff”. For me, the exhilaration of scientific enzyme composed of 5 RNAs and about laboratory uses are built in the lab and discovery stems from tackling biological 100 proteins. The spliceosome removes are controlled using custom software. problems with chemical or physical introns from precursor mRNAs, and this This means the microscope looks more tools that I have created. This synthesis process is a fundamental mechanism for like something put together with parts of the physical sciences (chemistry and encoding genetic complexity in higher from Radio Shack than anything you physics) with biology constitutes the organisms. After a few months in the might purchase from Olympus. While heart of my current research program. Moore Lab, I drank the “RNA Kool- this equipment can be used for a wide- Throwing everything but the kitchen Aid” and I’ve been hooked ever since! range of biochemical experiments, often sink (and sometimes that too) at complex When I began my postdoc, single the limiting factor is developing a system cellular processes is an approach that molecule experiments were just becoming suitable for single molecule imaging. was honed during my graduate work mainstream. However, the vast majority This is where a deep-appreciation of with JoAnne Stubbe at MIT. Often the of those experiments were carried out chemistry and biochemical “know how” experiments in JoAnne’s lab required on a single strand of RNA or with is enabling my laboratory to conduct

11 unique experiments. Combining machinery are lethal, defects that disrupt my laboratory. This involved an exciting traditional biochemical assays, cutting the recycling or biogenesis pathways can ride on the top of the freight elevator in edge chemical biology tools, and single lead to serious, incapacitating diseases the new Biochemical Sciences Building, molecule measurement is an extremely including retinitis pigmentosa or and this was by far the closest I’ve ever felt powerful approach for studying muscular atrophies. Finally, if there is one to being John McClane in “Die Hard”! molecular machines. I often describe my thing that I have learned during my career, Working at UW in the Department research as making radioactive molecules it is that making fluorescent molecules of Biochemistry has been an absolutely and then hitting them with lasers. is hard! We are devoting significant wonderful experience. The scientific At UW, I’m continuing to use effort towards developing new, enabling culture and heritage of the department and single molecule methods to study methodologies for attaching fluorophores campus is astounding and for someone various aspects of RNA processing. to RNAs or RNPs in vitro and in vivo. who works on RNA, I am humbled every My laboratory is focused on the initial Over the past year, I have recruited a time I step into the Khorana Auditorium. I stages of spliceosome assembly and wonderful trio of graduate students as well am particularly enjoying interactions with activation when the splice sites (locations as four undergraduates, and the laboratory new colleagues across campus in genetics, of bond cleavage and formation in the has started to take off! In January 2012, physics, chemistry, virology, or other pre-mRNA) are recognized by various we moved into our new laboratories in departments. The breadth of science at spliceosome components. How these sites the Biochemical Sciences Building (I UW is staggering and has already opened are correctly identified is a fundamental think we were the first lab to move in) my eyes to new directions for my research. question in gene expression since aberrant and in March, we began constructing Looking down the road into my future, I splicing by even a single nucleotide can our microscopes in remodeled space suspect that I will always be “making and alter the reading frame of the mRNA. in the basement of the 1985 building. measuring stuff” but given the pace of In collaboration with Sam Butcher and One particularly memorable event was scientific discovery at UW, I am even more David Brow, we have also begun to look figuring out how to maneuver a 12-inch excited to learn what that “stuff” may be. at spliceosome recycling and biogenesis. thick, 4' x 12' optical table weighing While many mutations in the core splicing 2000 lbs down the elevator shaft into

Clockwise from left: (1) Delivery of our optical tables by Reynolds Moving to the new BSB building in February 2012. (2) A view looking up the BSB elevator shaft from a ride on top of the freight elevator. (3) The Hoskins Lab CoSMoS microscope showing the red (633 nm), orange (594 nm), green (532 nm) and blue (488 nm) lasers and optics.

12 Alumnus Profile: Scott Lowe Scott Lowe, an Alumnus of the Department, recalls his time in Alan Attie's lab and his progression to cancer research in the Howard Hughes Institute. about experimental design. As time went Scott’s work resulted in important on, he changed projects in order to assist contributions to our understanding of the the lab in characterizing lipoproteins from a p53 tumor suppressor pathway and the mutant strain of pigs with high cholesterol. process of multi-step carcinogenesis. He There he also learned an enormous amount was among the first to recognize the role of about cell culture and receptor-ligand oncogene-induced senescence as a tumor interactions. Still, perhaps one of his most suppressive mechanism and has continued memorable experiences involved animal to pursue both the causes and consequences husbandry associated with propagation of of replicative death as it relates to tumor the mutant strains of pigs, which involved suppression. He made fundamental some amusing scenes involving artificial contributions to our understanding of insemination and drinking beer with a programmed cell death as an innate anti- new mother pig to enable her to tolerate tumor mechanism and as a response to Dr. Scott W. Lowe is Geoffrey Beene valuable newborns. He learned the value of chemotherapy. Most recently, he has helped Chair for Cancer Biology and Associate animal models of human disease, but also to found the comparative oncogenomics Director for Basic Cancer Research in the struggled with the challenge of the slow movement, combining novel mouse models Memorial Sloan-Kettering Cancer Center. pace of research with these systems. Much and RNA interference tools to filter the He is also an Investigator in the Howard of his more recent career has been devoted most important driver mutations from the Hughes Medical Institute. to developing more rapid strategies to study panoply of variation present in most human Scott’s scientific career began at the gene function in (smaller!) animal models. tumor genomes, and to identify cancer University of Wisconsin, where he initiated Scott’s time in the Attie lab was a time specific vulnerabilities that may serve as his undergraduate studies in chemical of key scientific development and gave him new therapeutic targets. After 16 productive engineering program. By the end of his the hunger to pursue a career in biomedical years at Cold Spring Harbor, Scott moved sophomore year, it was clear to him that research. Alan was a great mentor for him, to Memorial Sloan Kettering Cancer engineering was not in his future, and he teaching him a lot about the field, but Center, where he is active in the Program began to take a broad range of courses in an also gave him the freedom to explore his in Cancer Biology and Genetics. There, he effort to find a major. At that time his future own ideas. Scott’s time in the Attie lab was hopes to combine powerful genetic and trajectory was set by a series of events in the also one of great fun, and he made many animal modeling tools to develop better biochemistry department. First, he was friends in the Attie lab and throughout the cancer therapies. inspired by a Biochemistry course by Dave Biochemistry Department. He realized that Scott’s work has been recognized by Nelson, whose enthusiasm for the topic was science was a serious business but also had a number of awards. He was named as a contagious. This, together with a wonderful to be fun. He also realized that having a Sydney Kimmel Foundation Scholar and a course in Genetics given by James Crow good research environment is as important Rita Allen Foundation Scholar. He received made Scott interested in biochemistry and as having good ideas. These early lessons the Outstanding Investigator award by the molecular biology. Perhaps the single most helped guide his research throughout his American Association for Cancer Research impactive event in setting Scott’s trajectory career. and was awarded an American Association in research was triggered by his participation Scott applied to several premier graduate for Cancer Research –National Cancer in an honors lecture series associated with programs and was accepted into MIT…this Research Foundation Professor. He received Nelson’s biochemistry course, where he certainly was not due to his grades – which the Paul Marks Prize for Cancer Research heard a lecture from Alan Attie about suffered owing to an excess of time spent and the Alfred G. Kundsen award for cholesterol metabolism and lipoprotein at the Memorial Union – but rather the Cancer Genetics. He has also recently been biochemistry. At the end of the lecture, experience and productivity he had in the named an American Association for the Alan mentioned he had opportunities for Attie lab. He performed his graduate studies Advancement of Science Scholar. research in his lab, and Scott immediately at the Massachusetts Institute of Technology took him up on the offer. under the supervision of Dr. H. Earl Ruley, Scott Lowe in the Alan Attie lab Alan took him into the lab, where Scott and received his Ph.D. for research on completed a senior undergraduate project the role of the p53 tumor suppressor in and eventually stayed on as a technician. At oncogenic transformation, apoptosis, and that time, the Attie lab was located in the chemosensitivity. After a brief postdoctoral basement of the old biochemistry building position in the MIT Center for Cancer on Henry Mall, and then moved to the Research with Drs. David Housman and second floor. Scott’s first project focused Tyler Jacks, Dr. Lowe initiated independent on the contribution of de novo synthesized research at Cold Spring Harbor Laboratory, and exogenous cholesterol to various bile where he rapidly rose through the ranks acids. With this project, Scott learned a eventually becoming Deputy Director of range of methods, and importantly much NCI-designated Cancer Center. 13 Boyer Award Winner 2011 The Boyer Award is a generous donation of Paul Boyer, and is awarded to an outstanding post-doctoral fellow. Dr Boyer received his PhD from our department in 1943, and a Nobel Prize in Chemistry in 1997. Last year's awardee, Lars Renner, recounts how he came to Madison as a post-doc to study spatial localization of proteins and where it has taken him since. biomaterial surfaces. My Ph.D. research cardiolipin. Using the division protein was performed with Carsten Werner MinD as a model system, we demonstrated and centered upon the study of artificial that the behavior and function of this supported lipid membranes for the study protein in vivo is controlled by its of transmembrane proteins. After several interactions with cardiolipin (and anionic years of contact with Doug, I came to phospholipid) microdomains. The results Madison in 2009 as a DFG-funded from these studies provide a framework for Postdoctoral Fellow in the Weibel lab. I understanding the behavior of membranes fell in love with Madison, the seasons in in response to cell curvature and the role My love of cycling brought me to the Midwest, the beautiful landscape, the of phospholipid anisotropy in cellular Madison, Wisconsin. rolling hills for cycling and skiing, and the biochemistry. I met Doug Weibel in 2007 at a very special people in the Midwest. I was tremendously honored to receive meeting on the coast of Spain (Sant Feliu In Madison, I began studying a central the Boyer Postdoctoral Excellence Award de Guixols). Doug gave a talk at the question in cell biology: how is the in 2011 in recognition of this research. conference and I presented a poster on my temporal and spatial organization of the Paul Boyer’s foundational work in the graduate research, however I don’t think cell machinery established, maintained, biochemistry of ATP synthase inspired we spent much (or any) time discussing and replicated within the cell? Recognizing my interest in biochemistry and there is research. Our shared passion for cycling that numerous, functionally unrelated a loose connection between the proteins dominated our conversations. I kept in proteins localize to the poles of rod-shaped that I have worked on and the proteins for touch with Doug after the meeting and our bacterial cells, I explored whether the mean which Paul Boyer received the 1997 Nobel paths crossed annually, including a one- curvature of this region of the cell wall Prize in Chemistry. week cycling excursion through the Italian plays a role in biomolecule localization. I In 2012, I took a position as a Group and French Alps. During the course of our used techniques from material engineering Leader in Molecular Nanosensors at the interactions, I became interested in using to test whether membrane strain at the Technical University Dresden. I returned my background in materials science and polar regions of bacterial cells influences to Dresden with an extended family polymer science to study microbiology. phospholipid heterogeneity and the (including my American-born daughter I studied Bioprocess and Chemical localization of amphipathic proteins. Charlotte), a cache of fond memories of Engineering at the Technical University Our results were consistent with a model Madison, and several new bikes. I remain Dresden, Germany. After receiving my in which membrane curvature created an avid cyclist and am certain that cycling diploma I worked as a Research Associate strain and positions microdomains of the will play an instrumental role in my future at the Leibniz Institute for Polymer intrinsically curved, anionic phospholipid visits to Madison. Research Dresden and the Max- Bergmann-Centre for Biomaterials studying protein adsorption on

Methodology: A-E application of soft lithography to fabricate microstructures that we used to analyze the temporal and spatial behavior of lipids and proteins in bacterial cells. F-I Bacterial cells are adapting to the imposed geometry.

14 Dave Nelson: Researcher, Teacher and Collector A perspective on an exceptional historian of UW and our Department. Adapted from the original article By Nia Sathiamoorthi of the Daily Cardinal

A room in the Biochemistry Building was known but before the code was really of them. “Before long, everyone in the overflows with scientific equipment – the worked out. So, everyday somebody would department knew if they had a piece of dull glint of old microscopes and beakers on come in the door shouting, ‘They’ve got junk, they should bring it to me,” Nelson every available flat surface. Hidden behind phenylalanine,’ or something else from the said. this hodgepodge sits Professor Emeritus code. It was just intoxicating.” The equipment is an important feature David Nelson. After receiving his Ph.D., Nelson traded in a College of Agricultural and Life Nelson is a collector of old laboratory the West Coast for the East Coast when he Sciences course, Inter-Ag 375 Ground instruments. Those in his office are simply a started his post-doctoral work small fraction of his stockpile, overflowing at Harvard Medical School in many rooms and closets on this campus. It Eugene Kennedy’s laboratory. is because of Nelson’s love for science and Nelson found Kennedy’s the University of Wisconsin-Madison’s broad approach to research rich academic history that this collection very different from Kornberg’s continues to grow. narrow-focused one. While Nelson was born and raised in Fairmont, he acknowledged both were Minnesota, and it was in this small town he important, Nelson favored discovered his appreciation for the sciences. breadth in his own laboratory He credits his good teachers, especially when he became part of the his high school chemistry teacher, with UW faculty in 1971. spurring his excitement for chemistry. It was the research on “I took things apart and put them back bacterial attractants and together. I was a ham-radio operator. But repellents by another prominent basically, it was chemistry that I loved,” UW professor of biochemistry, Nelson said. Julius Adler, that first brought Nelson pursued his undergraduate Nelson to Wisconsin and studies at Minnesota’s St. Olaf College. inspired him to study the free- Majoring in both biology and chemistry, swimming unicellular organism he ultimately realized his desire to study called paramecium. medicine or the underlying causes of After jump-starting his own laboratory, Breaking Research in Life Sciences at UW: behavior. He was all set to go to medical Nelson began his teaching career with Past and Present, facilitated by Nelson and school until the summer of his senior year Biochem 501. He appreciated how the other professors. In the course, the first when he worked full-time in a research class forced him to know the entire field discussion of every week revolves around laboratory. Nelson discovered he loved and gain the vocabulary to converse with historical discoveries and the second working in the lab and nothing else came any colleague, regardless of research topic. discussion focuses on the current UW close as a real challenge or pleasure. He Twenty years later, Nelson had the research derived from those discoveries. changed his plans suddenly and went to opportunity to teach for a year at Spelman The lab allows students to repeat historical graduate school at Stanford University. College, a small African-American women’s experiments with historical equipment. Nelson joined Arthur Kornberg’s college in Atlanta. He discovered he loved Teaching this course inspired Nelson to laboratory in 1964. Just a few years prior, the depth achieved in teaching a smaller consider authoring a book on the history of in 1959, Kornberg received the Nobel course so much he almost stayed on, but science at UW-Madison. Prize in Physiology or Medicine for his returned to UW to create a longer two- “I love biochemistry and I love to discovery of DNA synthesis mechanisms. semester biochemistry course, 507 and 508, teach. What motivates me, as it does most Under Kornberg, Nelson studied the use with his teaching partner, Michael Cox. teachers, is seeing the lights come on in of bacterial sporulation as a model for cell It was with Cox that Nelson took on their eyes. Students take both biology and differentiation. When bacteria form spores, the revision of Lehninger’s “Principles of chemistry, and in biochemistry, they see it a part of the cell pinches off to make that Biochemistry” textbook. “It has been a finally coming together,” Nelson said. “I spore. We now know a new set of genes really fabulous partnership. Dave really hope what students learn from my teaching, is expressed, but Nelson’s group was still cares about the book and teaching,” Cox both in class and the laboratory, is a healthy asking the simple questions about cellular said. The book, in its fifth edition and respect, maybe even an awe, for life.” differentiation. produced in 12 languages, has become the “At Stanford, I was a greenhorn in a most widely used biochemistry textbook in To see the original article, published parade of first-rate people. But they took us the world. March 19, 2013 in its entirety, please visit: graduate students on as equal colleagues,” Nelson actually came into his collection http://host.madison.com/daily-cardinal/ Nelson said. “I was there at a wonderful of old scientific instruments from a retiring science/dave-nelson-researcher-teacher- time. This was after the structure of DNA UW professor, and grew to see the beauty and-collector/article_a9f7d6b8-910e-11e2- 90cd-001a4bcf887a.html 15 D and D Break New Ground Hector DeLuca's lab continues to develop Vitamin D analogues with exciting therapeutic potential for kidney dialysis, autoimmune disease and diabetes. Never mind the caused by hyperparathyroidism. At the MS. This, therefore, has moved our focus title -- that's the same time, learning the lessons of 2MD away from vitamin D onto ultraviolet light editor's fault. It is we have been developing new analogs that and its possible use in suppressing MS. true though that possess the ability to synthesize new bone Another topic of great interest has been our laboratory does in vivo but with reduced ability to cause type 1 diabetes. Previous work in our group remain functional bone resorption. We feel these compounds clearly showed that vitamin D deficiency in the area of will increase bone mass in osteoporotic markedly increases incidence and severity Vitamin D -- with patients and could be the next generation of type 1 diabetes in the NOD mouse (the a special focus on of development of vitamin D compounds animal model of this disease). Of great the development for this widespread disease. interest is that the islet cells of the pancreas of new pharmaceuticals based on the A major focus is in the area of contain large amounts of the vitamin D Vitamin D structure. Currently through autoimmune diseases. We have focused receptor and in addition to its role in the external support, we maintain a group of for the last 20 years on multiple sclerosis immune system, the vitamin D hormone synthetic organic chemists who prepare (MS) and have first been enamored by plays an important role in the cells that new and interesting analogs of the the possibility that vitamin D might produce insulin. We found an analog of vitamin D structure, which we hope will be involved in protecting against MS. the vitamin D hormone that will suppress have specific biological activities. Several However, our group as well as another type 1 diabetes in the NOD mouse. We of these analogs are in various stages group in France have clearly demonstrated have preliminary evidence that this analog of development in the pharmaceutical that vitamin D deficiency does not will stabilize transplanted islet cells into pipeline, and especially our lead compound increase the incidence of experimental animals that have lost their natural islet called 2MD which is 2-methyelene-19- autoimmune encephalomyelitis (EAE, cells through autoimmune disease. nor-20(S)-1a,25-dihydroxyvitamin D3. a model of MS in mice) but rather Another area of interest has been the It was designed initially for treatment of suppresses it. Furthermore, elimination of relationship between diet and the incidence osteoporosis but more recently we have the vitamin D receptor in such animals also of type 1 diabetes in the NOD mouse. We found it promising for the treatment of eliminates the incidence of disease. Thus can clearly show that a chow or crude diet secondary hyperparathyroidism in dialysis unexpectedly, vitamin D deficiency in this causes almost a 100% incidence of type 1 patients. 2MD is extremely effective in autoimmune disease results in reduced diabetes in the NOD mouse. If the same increasing bone strength in ovariectomized incidence, contrary to experiments or mice are placed on a highly purified diet rats and in monkeys. It has gone through surveys that show a correlation between with a particularly highly purified casein as phase 2 clinical trials in human patients. high blood levels of 25-hydroxyvitamin a protein source, the incidence is near zero. Although it did not increase bone mass, D and reduced incidence of MS. Further We have prepared extracts of the natural it greatly increased bone turnover that we examination of this has resulted in our diet that when added to the purified diet strongly believe results in a much stronger discovery that a wave band of light that will restore the high incidence of type 1 skeleton. Unfortunately to develop a drug does not produce vitamin D is responsible diabetes. An interesting and important for osteoporosis requires a 3-year, phase for protection against EAE and presumably project is to try to find out what it is in the 3 fracture study costing approximately crude diet that supports the development $1 billion. So far we have been unable of type 1 diabetes in these susceptible mice. to locate a firm willing to commit to To summarize, we are still having this amount. We have, therefore, focused a lot of fun with vitamin D and we our attention in a shorter goal, namely are very interested in the autoimmune the treatment of bone disease of kidney diseases and what could be done to help failure patients who lack the ability to in their therapeutics. In the meantime, produce the vitamin D hormone in any a major effort is the timely development quantity. This compound is currently in of pharmaceuticals for the treatment of a a phase 2 clinical trial in dialysis patients variety of diseases, especially bone disease to correct their metabolic bone disease resulting from kidney failure.

VDR ligand-binding domain.

16 Henry Lardy, Bob Burris, Van Potter South Dakota’s Gifts to the UW. By Professor Dave Nelson One research work at UW following his graduation research career studying this process laboratory at in Agriculture and Dairy Science from and the bacterial enzyme (nitrogenase) South Dakota SDSU in 1939. As an undergraduate, that catalyzes it. Over his long career State College Lardy, too, had worked in the laboratory he trained 71 graduate students and (SDSC, now of Moxon on problems related to a similar number of post-docs. Burris SDS University) selenium toxicity. Lardy earned his served as Chairman of Biochemistry was responsible Ph.D. with Paul Phillips at the UW in from 1958 to 1970, was elected to the for starting the 1943, and joined the UW faculty after National Academy of Sciences (1961), careers of three a postdoctoral period. Lardy and Burris was awarded the National Medal of distinguished worked in the same UW department Science in 1979, and won the Wolf UW professors in the life sciences: (Biochemistry) from the 1940’s until their Award in Agriculture (often considered Van Rennselaer Potter (who joined the deaths in 2010. So Potter, Burris, and the Nobel Prize in Agriculture) in 1985. faculty of the McArdle Laboratory in Lardy all got their starts in the Franke/ 1940); Robert H. Burris (who joined Moxon selenium laboratory at SDSU. the Biochemistry faculty in 1944) and Henry A. Lardy (Biochemistry/ Enzyme Institute, who joined the faculty in 1945). Van Potter, born in 1911 on farm near Coteau des Prairies, South Dakota, earned his B.S. in Chemistry and Biology in 1933, then took a position in the chemistry laboratory at the SDSC Agricultural Experiment Station under Professors Kurt Walter Franke and A. L. Moxon. Franke and Moxon used chemical methods to determine, in feeds and tissues, the levels of selenium, which caused “blind Van Rensselaer Potter (1911 - 2001) staggers” in farm animals. Potter’s next move was to become a graduate student in Van Potter spent his entire career Robert H. Burris (1914 - 2010) Biochemistry at the UW under professor studying enzyme levels in transplantable Conrad Elvehjem, earning his Ph.D. in animal tumors, and the effects of various Henry Lardy was a member of the 1936. After postdoctoral work, he joined inhibitors on enzymes of tumors. Today’s UW Biochemistry Faculty and one of the McArdle Laboratory at the UW. practice of combining several inhibitors the original Co-Directors at the Institute Robert H. Burris grew up a block away in cancer therapy is derived in part for Enzyme Research when it opened in from SDSC in Brookings, and earned his from Potter’s work. He was elected to 1949. Lardy made research contributions B.S. in Chemistry there in 1936. He and the National Academy of Sciences and in many aspects of metabolism. In his Van Potter became acquainted at SDSC, was president of the American Society doctoral work with Paul Phillips, Lardy where Burris also worked in the Franke/ for Cell Biology in 1964. His second developed a medium that maintained the Moxon lab. While Burris was still an serious interest was in the field he named viability of bull sperm for long enough undergraduate, Potter, by then already at “bioethics”, and his book Global Bioethics, to be used to artificially inseminate the UW, recommended him for a summer published in his retirement years (1988) cows far away from the bull, enabling position in the laboratory of Perry Wilson showed the way for much of the modern the wide dissemination of the genes of a (UW Bacteriology). Wilson, pleased with effort to bridge science and humanities. prize animal. For this early work, he won Burris’ work, invited him to come back the Wolf Award in Agriculture (1981). to the UW as a graduate student, which Bob Burris learned, in the laboratory Over the rest of his career he he did, finishing his Ph.D. in 1940. of Harold Urey, to measure the conversion continued his studies of respiration in Henry Lardy, a native of rural Roslyn of 15-N-labeled N2 to NH3 by nitrogen- spermatozoa; shared in the discovery of South Dakota, also began his graduate fixing bacteria, and then spent his whole biotin function; studied thyroid toxicity 17 transferring enzymes; career, and won a number of prestigious and studied the awards in addition to the Wolf Award. regulation of Outside the laboratory he was a gluconeogenesis in committed social activist; during the detail. He worked in McCarthy Era in Wisconsin, Lardy his laboratory every was president of Citizens Against day until shortly McCarthy, and his last public lecture before his death at included his strong plea to end the 92 in 2010. During discrimination against gays and lesbians. the last decade of his research career he Lardy’s attitude toward research entered a new area, is captured in this typed sign, which the metabolism of was pinned to the wall in his office: the human steroid DHEA and the effects “Beginning February 1st 1958 and of its metabolites on effective thereafter, working time which cellular processes. is lost while preparing for examinations should be deducted from your vacation Henry A. Lardy (1917 - 2010) Ironically, one of the potential uses for allotment. Anyone qualifying for and the thyroid hormone; made major such metabolites was the treatment of advanced degrees should be able to contributions to the understanding of the prostate cancer, the cause of Lardy’s death. acquire his scientific knowledge during class periods and leisurely evening coupling of oxidation to phosphorylation During his long career, Lardy reading. Knowledge gained while in mitochondria, and of uncoupling by trained 64 graduate students and 110 re-reading class notes is either false agents such as dinitrophenol; defined postdoctoral fellows, and published or short-lived. What you learn at the and studied respiratory control in more than 500 papers! He was elected laboratory bench is yours forever and mitochondria; purified, crystallized, and to the National Academy of Sciences may even benefit the rest of mankind.” characterized a number of phosphate- in 1958, just thirteen years into his

The Beckman DU Quartz Photoelectric Spectrophotometer was an instrument that revolutionized biochemistry and was used by all three of the South Dakotans.The Beckman Model DU was the first ultraviolet and visible spectrophotometer. Introduced in 1941,this instrument retained essentially the same design until it was discontinued in 1976, a commercial lifetime of 35 years.

18 International Programs: Giving Our Undergraduates a Global Perspective Three innovative programs enhance the Biochemistry Department's undergraduate education by creating hands-on experience on three continents. By Professor Marv Wickens

Every practicing scientist knows that science is international. It is not just that the conclusions we reach are universal. It is also that great results are Each program faces important obtained across the world, that collaborations extend to many continents, challenges as it builds on its strengths and that each culture builds on its own strengths, perspectives and history. and moves into new areas. We seek your Scientists, companies and policy-makers greatly benefit by having first- support to enhance these rare strengths in hand knowledge of these other cultures. Three innovative programs in the undergraduate training in Biochemistry. Biochemistry Department now provide that for our undergraduates. Each program has a unique emphasis, and can have dramatic impact 2 The Khorana Program is expanding on the students who participate. The Khorana Program (Dr. Ansari) brings into new areas of science, and seeks support students from India to UW (and now other institutions). Through new for UW students to go to India. initiatives, it now also enhances agriculture and Tech Transfer in India, 2 The SCORE program is soon drawing on the expertise of the Department, the UW, and WARF. The going to include additional outstanding SCORE Program (Dr. Wickens) sends talented UW undergraduates with institutions elsewhere in the world, and a serious commitment to science to study in Cambridge and Oxford, has begun to develop year-long experiences committing themselves to an intense summer of research. The Uganda for our most gifted majors. Program (Dr. Ntambi) sends students to that African nation, to learn first- 2 The Uganda program looks for hand how biochemistry and nutrition impact Uganda’s health care. Each of stable funding for its students to have an these experiences come at a formative time in an undergraduate’s life – and eye-opening experience in human health. so has ripple effects into the future. The three programs engage the UW in the international community of If you have suggestions or wish to science in a different way than our extensive scientific collaborations. They contribute, please contact Betty Craig send some of most exceptional students out into the world and let the rest (Department Chair) or any one of the of the world know that UW has something special to offer. three heads of the programs: Aseem Ansari This year, the creators of the programs describe recent developments (Khorana) Marv Wickens (SCORE), and the impacts the programs have on students. We also have asked the James Ntambi (Uganda). students to speak for themselves, and explain in their own words how their participation changed their lives. Please see page 66 for contact information.

19 The Khorana Program - India New initiatives and growth in this program further extend the Wisconsin Idea to India, and intimately link our department and the UW with that burgeoning culture. By Professor Aseem Ansari The University Khorana scholars learn about each RajBhandary, Gobind’s close colleague of Wisconsin other’s research projects in meetings every and friend, brought MIT onboard. –Madison week, which typically last 4-6 hours. Georgetown joined soon thereafter and (UW), in close Beyond science, we arrange talks and several other universities have expressed in partnership with meetings with exceptional individuals interest in partnerships in the near future. the Government across a wide range of disciplines. These To commemorate Gobind’s passing on of India and the have included: November 9th 2011, the Government of bilateral Indo-US • Sam Pitroda, the father of India’s India doubled the scope the program and Science and telecom revolution and advisor to India’s extended the funding for another three- Technology Forum (IUSSTF), initiated a Prime Minister, inspires scholars to think year cycle. Private funds bring the total scholar exchange program in 2008. This big; number of scholars to about 40 per year. prestigious research internship program Each of the ten partner schools received was named after Har Gobind Khorana, • Carl Gulbrandsen, managing Director 3-5 students. Cohesiveness is maintained an Indian-American scientist who of WARF, discusses how scientific ideas through an orientation event at UW, pioneered the use of chemical approaches can change the world; weekend video conferences, and an annual to solve fundamental biological questions. • Krishna and Suchitra Ella encourage symposium in Delhi at the internship's Gobind epitomized the importance of students to take the path less travelled, end in early August. The community transcending scientific, cultural and describing creation of an Indian vaccine is close-knit, helping foster future geographic boundaries (see Khorana company that has made vaccines international collaborations and seamless biography on page 38). affordable to the world’s poor; bridges between scientific communities To celebrate Gobind’s contributions, • Richard Davidson, a neuroscientist across the globe. we developed a program guided by the inspired by the Dalai Lama, has revealed Khorana Technology Transfer Program following principles: the remarkable ability of meditation to Scientists in the Department of • Identify and nurture future “Khoranas” alter the brain; Biochemistry have excelled at finding commercial applications for their scientific building long-term bridges between • Gerald Chan, a billionaire biotech discoveries. From the outset, Minister scientific communities, investor with a PhD in Biophysics from Sibal saw parallels to the tech-transfer Harvard, has emphasized the importance • Extend the Wisconsin idea to challenges India faced. These similarities of passion in the creative process. India, focusing on sustainable rural led to the Khorana Technology Transfer development, In addition, several scientificProgram, in which India sends a mix of • Partner with industry to develop visionaries, including Nobelists Phil excellent scientists and policy makers innovative products to meet needs across Sharp, Ham Smith, and Gobind, have "to learn how a government supported the globe. shared their own scientific journeys as institute such as UW can generate such have diplomats and entrepreneurs. All is IP and commercialize it so successfully." Future “Khoranas” aimed to nurture bold thinking among India overlooked other highly visible A key goal of the program is to ignite the students. schools to launch the Khorana Tech- the imagination of talented students Several Khorana scholars won awards Transfer Program (http://indousstf.org/ from US and India. Selected students are for their research. The quality of their work Khorana/khorana.html). The program invited for summer internships in leading is also reflected in the surprising number of leverages WARF’s unique strengths in laboratories. US students work in some of publications and patents that have resulted commercializing scientific advances and the best labs in India, and Indian students from a short summer internship. the UW-Business school’s Weinart center who are selected from a nation-wide Expansion and doubling down for entrepreneurship. search work in top labs at UW and its 10 In early 2010, due to the overwhelming An intensive two-week course in US partner universities. The participating increase in high quality applicants, UW 2012 was tailored to the Indian context. labs in both countries are world leaders invited the group of Big 10 Midwestern Home institutions were incentivized to with reputations for nurturing talent. schools that form the “Committee on make investments so that their trainees Scholars work with senior lab members Institutional Cooperation” (CIC) to would be able to create the necessary on specific projects. Our central goal is join the Khorana Program. We took a entrepreneurship and innovation for students to learn to frame scientific delegation of Deans from several CIC ecosystem. Ambitious, yes! However, the questions and experimental paths to schools to meet Minister Sibal in March opportunities for India to build on its answering those questions. Along the of 2010. It took nearly 18 months to intellectual strengths and demographic way, many make remarkable research meticulously assemble the framework dividend are enormous as are the potential breakthroughs. of the shared program. Professor Tom benefits to the US and India. 20 Rural Development numbers of "non-Biotech" Another major goal of the Khorana and "Agriculture, Dairy and Program was inspired by the Wisconsin Food Security" scholars. Idea – that research at the university Taken together the numbers should benefit the public. We took the would approach the volume of Idea half way across the globe and applied Fulbright scholars who travel to lessons learned in Wisconsin to improve India to learn about her culture Rural conditions in one of the poorest as well as her spiritual and social parts of the world – the eastern edge of UP, structure. A thriving partnership India’s largest state with nearly 300 million requires that US students travel people. The USAID and three Indian to India to learn how innovative Late Prof. Har Gobind Khorana interacts with institutions sponsored this project. John technological advances are transforming some of the 2009 of Khorana Scholars. Peters, the Director of Soils Testing lab at India. For that we continue to seek your The absence of a reasonable stipend that UW, boldly chose to relocate to India. John advice and support. most UW undergrads rely on to cover the and his wife lived and worked in India for An unexpected challenge: extracurricular costs through the academic two years and established 100 soil testing Funding Passages to India year turned out to be a serious problem. labs where less than 5 labs existed across Funds for the Indian Khorana scholars Consequently, we are seeking potential the nation. Best agricultural practices were are generously provided by Government sources of funding to be able to provide developed and shared with thousands of of India’s DBT and IUSSTF. To our utter a stipend and airfare to future American farmers. Women were taught to maximize surprise we found virtually no support Khorana scholars. We want to reach equal milk production and use funds to support to send US Khorana scholars to India. reciprocity of scholars between US and their family. For details see: NSF and NIH were enthusiastic but India and welcome creative ideas. http://news.cals.wisc.edu/ offered little financial support. IUSSTF communities/2012/10/22/helping- has temporarily stepped in to fill the For more information on the Khorana women-help-themselves/ void. We set out to find 20 talented UW Program, please contact Aseem Ansari Expanded scope and impact students but were only able to identify ([email protected]) and We now plan to expand the scientific 4-5 highly qualified students who were Nishritha Bopana (nbopana@indousstf. scope of the program, funding similar interested in going to India for research. org).

The SCORE Program - Britain Undergrads enhance their passion for science and gain international perspective through an intense summer experience in Oxford and Cambridge. By Marv Wickens, with a past participant, Amanda Buyan For two intense passion for research is heightened by the intensity of the summer’s focus on science. Most months, the students are even more committed to science than they were when they left. work in laboratories, Amanda Buyan, a past participant in SCORE, is now is doing her PhD work in conducting research Oxford, and writes about her experience in the program. in a specific lab, attending seminars I was elated when I got that email saying that I’d been accepted. It was a chance to and participating in scientific fulfill my dream of going to England, and to do research at Oxford – a great university discussions. and as I soon discovered, a beautiful place as well. It was the first real chance I had seen They study a broad range of problems at UW to study abroad as a science major, without extending my time to graduation. in biochemistry, molecular biology and would)The program be doing gave as mea PhD the candidate. chance to do a short, 8-week research project for which I genetics. The mentors are outstanding, and would work full-time – a rare glimpse of what kinds of things I could (and eventually have included Fellows of the Royal Society and EMBO, and a Nobel Prize recipient. The experience was even richer than I had anticipated. The lab work was intense The program enables students to and satisfying. Oxford was full of European scientists and I traveled a bit, seeing other see science and themselves through an cultures at a personal level. I became convinced I would continue to do research in the international lens. Most of the students next phase of my life. That phase was catalyzed by SCORE. While at Oxford, I inquired about PhD have not traveled outside the US before. opportunities there, my SCORE professor (Mark Sansom) recommended I apply for a On their return, students often comment Wellcome Trust Structural Biology Programme at Oxford. I ended up being one of the that they have gained a deeper appreciation five fortunate people that they select, allowing me to exceed my wildest dreams and for how much they love science itself. Their pursue a PhD at Oxford for four years in England. I may still be having a few difficulties with the British sense of humour, but love and appreciate what SCORE did for me. 21 Anticipation from two participants before they leave for SCORE 2013…

Having never been out of the country, I'm excited…to gain new perspective on the world. And even more excited that will be able to build on the science skills I have gained at UW-Madison. Ryan Birschbach

Studying a new disease model, experiencing the rich history England has to offer, working with brilliant researchers - I could not be more eager to get started on this journey. The Cambridge Backs Sarah Larson New initiatives now seeking funding include expansion to other leading institutions in Europe and around the world. It goes without saying that this requires stable funding, and we seek your support to enhance the programs and provide financial stability.

The Uganda Program UW students gain a deep understanding of the importance of nutrition and biochemistry in a poor but inspiring country. By James Ntambi, with past participants Beth Stadtmueller, Alex Burford, Matthew Hunt and Eric Monroe The Ugandaon a trip west to visit the Queen Elizabeth Program enables National Park, Kabale, and Lyantonde. students to In Uganda, students come face to face As a Junior and a Biochem major, at examine health with the reality of HIV/AIDS, women’s UW, I found myself challenged by a major and nutrition in a health, and nutrition. Over the years, life decision – What next? I weighed post- graduation options -- find a job, travel, go developing country. largely due to Dr. Ntambi's connections, to grad school, or maybe join the Peace Prior to leaving the strong bonds have formed between the Corps. Two main interests shaped my country, students University of Wisconsin-Madison and decision – a fascination with the molecular enroll in a three Uganda's Makerere University and the world, and a deep desire to help the world credit course focused on the Ugandan Institute of Public Health. Through these around me. At the time, it was difficult to healthcare system and culture. Topics relationships, students gain a truly unique identify a path that satisfied both interests. cover everything from economics to child exposure to the intersection of politics, Then my advisor, Dave Nelson, introduced malnutrition, prenatal care, women’s economics, culture, and education as it me to James Ntambi, who was developing a health, education, agriculture, or any other relates to public health. A past participant, new program in Ugandan public health and field found interesting to the student. Beth Stadtmueller, describes how the nutrition. I jumped at the opportunity, and changed forever as a result. The end of the fall semester culminates program impacted her life. Visiting Uganda in late 2002/early 2003 with a three week adventure in was an intense experience. I had traveled Uganda. The journey begins in extensively and had witnessed poverty the capital city, Kampala. While prior to the trip, but my experiences here, the group tours the city, had never brought me face to face with visits the largest hospital Uganda a public health crisis, nor provided an has to offer, and speaks with integral course of study, as the UW Uganda different healthcare workers. program did. Upon setting foot in Uganda, Time is allotted in the evening it became clear that political unrest, limited resources, malnutrition and disease were for students to explore the city’s incredibly intertwined – much more fantastic markets, restaurants, so than is obvious in publications. The and culture. After spending time situation might have seemed hopeless in Kampala, the group departs UW students at Mwanamugimu Nutrition Clinic. were it not for the impeccably high spirits of the Ugandan people, their enthusiasm to 22 learn and their remarkable ability to create If you are looking for amazing people, once in a lifetime experiences, or a better understanding of this big world we all share, I highly recommend the Uganda Program. Alex Burford (2004/2005 program alum)

UW students in rural classroom.

The formal program is a collaboration with limited resources. I was humbled. And I would never see life the same again. I recall severely ill people asleep on the hallway floors in Mulago hospital, which between the Biochemistry and Nutrition lacked not only enough beds for its patients, but also many basic medical instruments and Departments, and the CALS Office in some areas, even running water. I tracked a patient’s progress in the Mwanamugimu of International Programs. As Beth's nutrition unit – her name was Jabeth – she was just over a year old, yet was already comments illustrate, it enables students to battling severe malnourishment, HIV, Tuberculosis and malaria. Jabeth was one of many connect classroom studies with real-world children in the unit whose prospects for the future seemed dim, yet the unit staff was learning. The students gain a palpable unfailingly upbeat and their approach of combining nutrition education for mothers understanding of the realities faced by so with treatment of children was highly effective, promising a brighter future for many. many in the world. Students collaborate As the eye-opening experiences piled up, I could see that education was the intimately with villagers, who in fact strongest weapon in use to battle the complex set of circumstances at play in Uganda, yet education itself was also suffering. Even at our host institution, Makerere University, identify the projects that are needed. resources were limited. As I walked through campus, I sensed much of the same The program needs financial support positive, youthful energy and motivation as at UW, but in contrast the laboratories for to continue. With that in mind, the science education and research contained instruments in need of repair and were void student alumni themselves created The of many basic necessities. Overall it was clear that Ugandans failed to benefit from much Village Health Project. This program of the education and research that was being conducted throughout the world and this directly raises funds, applying for grants observation concerned me and left a truly lasting impression. and fellowships , and seeks donations. The Uganda Program provided me with a new and global perspective on life and the To donate, please send a check to: career decisions before me at the time. Having observed the complexity of a public health Village Health Project, 333 East Campus crisis, the discrepancy between biomedical research and its global application, and the Mall, Room 3207, Madison, WI 53715- power of education to promote change I concluded that pursing a career in academic science would be the best way for me to help combat the challenges facing Uganda and 1380. For more details concerning many other parts of the world. Upon returning from Uganda I began graduate training the international health and nutrition in biochemistry and today I am a postdoctoral researcher studying the human immune program in Uganda please contact system, research that I hope to expand upon in my own laboratory one day. It has been John Ferrick ([email protected]) ten years since I set foot in Uganda, yet much of what I learned remains at the front of Director of International Programs at my mind today – motivating me to pursue research that will help to combat disease and UW-Madison/College of Agricultural & inspiring me to ask how science education can be expanded to train studentsBeth Stadtmueller worldwide Life Sciences. and ensure that discoveries become accessible to everyone.(2002/2003 program alum)

The Program was eye-opening. Several of us who had been moved by the experience The experience motivated me to join the formed a 501(c)3 nonprofit group, the Village Peace Corps as a health educator on projects Health Project. Thanks to involved students and relating to HIV and maternal and child the generous support of alumni, the Wisconsin survival. I now am preparing for a career in Idea Fellowship, and Rotary International, the medicine working here and abroad. Looking organization now supports sustainable projects back, it is clear that the Uganda Program to improve sanitation, nutrition, and education expanded my worldview, and instilled passions in rural Uganda. for global public health and social justice. Eric Monroe Matthew Hunt (2010/2011 program alum) (2004/2005 program alum)

23 Pre-college Outreach The Wisconsin Idea asserts that developments at the University should be brought to the benefit of the people of Wisconsin. Two innovative programs created by Drs. Hazel Holden and Doug Weibel of the Biochemistry Department do just that, with a focus on the education of middle school and high school students. Here, Dr. Holden describes a program in which middle school students participate in research in her own lab, yielding astounding results all the way from crystals to structures to papers. Dr. Weibel describes his program’s collaboration with a committed high school teacher, and the ripple effect that has had on her students. Project CRYSTAL Middle school students gain hands-on understanding of chemistry and biochemistry by doing crystallography - and publishing papers - in Hazel Holden's lab. Project CRYSTAL The 2011-2012 Project CRYSTAL the structure and function of an enzyme is a scientific class was composed of four seventh involved in unusual sugar biosynthesis, is outreach program grade students, Melissa, Malaika, Gwen, off to a great start. The cloning has been first establishedand Sarah, from Edgewood Campus going well, and purified protein is expected in 2009 through Middle School. IPiB graduate students within the next coming months! funding by the NSF Rachel Kubiak, Becky Phillips, and During the 2012 summer months, the to the laboratory Matthew Zmudka mentored these middle Project CRYSTAL team began production of Dr. Hazel M. schoolers. Through their efforts, they of a biochemistry textbook specifically Holden. The name were able to clone, purify, crystallize, and geared towards middle school students. “CRYSTAL” solve the structure of a protein referred Thus far six chapters have been written and stands for to as ChmJ. It is a fascinating enzyme illustrated. Members of this year’s class are Crystallographers involved in the biosynthesis of mycinose, serving as reviewers, and their comments Researching with an unusual sugar found attached to the have been terrific. It is already clear that Young Scientists: antibiotics chalcomycin and tylosin. A this book is making a profound difference Teaching And paper describing their results has now been in how fast these students are learning the L earning.” accepted for publication in Biochemistry, concepts being taught during the lectures. The programwith all four middle school students serving Project CRYSTAL has now been provides hands-on as co-authors. This is the second time that featured as one of the NSF exemplary laboratory experiences for four selected middle school students in this program projects and has been highlighted by the middle school students each academic year. have been authors on a paper published in National Science Teacher Association. It They spend approximately 1.5 hours in the Biochemistry! It was a bittersweet moment has also been written up in Science Daily, laboratory per week working on a specific for all of the Project CRYSTAL team when C&E News, Inside UW-Madison, and the research project. Through both laboratory “graduation day” arrived because these RCSB PDB Newsletter. Recently, Project exposure and interactive lectures, these young women brought such enthusiasm CRYSTAL was cited by Prag Chitnis, students learn the fundamentals of and laughter to the laboratory each week. director of the Division of Molecular chemistry and biochemistry. At the Project CRYSTAL began its 2012- and Cellular Biosciences at the National end of the school year they leave the 2013 season on September 11th with four Science Foundation, for its broader impact Holden laboratory having experienced eighth graders, Odoi, Malachi, Rosie, and component. We are happy to announce such techniques as DNA cloning, E. coli Lilli, from Spring Harbor Middle School. that Project CRYSTAL was refunded for cell growth, protein purification, X-ray Their project, which also involves studying an additional three years. crystallography, and protein modeling. More details concerning Project CRYSTAL can be found at its Facebook page: (http://www.facebook.com/ProjectXTAL) or at: http://www.projectcrystal.org/.

Graduation Day! The class enjoyed ice cream The 2011-2012 Project CRYSTAL Class. at Babcock with their mentors. The 2012-2013 Project CRYSTAL Class. 24 MicroExplorers The thrill of discovery excites high school students about science through a collaboration between a high school teacher and Doug Weibel’s lab. MicroExplorers participated in a range of activities in 2012. A highlight was our collaboration with We caught one another in the act: sizing up the long row of tall green lockers. local chemistry Would we fit inside, if stuffed in? It was crazy to think that we would be nervous, however none of us had particularly fond memories of high school and biology chemistry. Does anyone? As we were about to relearn, fantastic teachers can have a high school transformational role in chemistry (and science) education. teacher, Melissa Around the corner, past the lockers, a jolting vision awaited: a standard, public Hemling. Melissa high-school lab. It probably looked about the same when we were in high school, returned for her however it looked very different from the environments to which we have become second summer accustomed that are sparkly, dazzling, and full of blinking lights and very expensive as an intern in stuff. The high school lab was old and plain. Melissa was about to transform this the Weibel lab space with her energy and creativity. Over the summer, Melissa designed a set of through the NSF- experiments to introduce her students to microfluidic devices and we were here to funded, Research work with the students on these activities. By the end of the hour we spent with each class, students designed and made Shrinky Dinks and used them to create microfluidic Experience for devices in a transparent silicone elastomer that they would use to perform acid-base Teachers program and she was on a chemistry experiments. Using an iterative approach, the students learned about the mission to integrate microfluidics into laminar flow of fluids through hands-on activities, and used it to design, create, and her classroom. Microfluidics is the test microfluidic devices to solve a chemistry challenge provided by Melissa. study and application of fluid flow at I was assigned to hang out with a group of four girls for the class period. As we the microscale. The physics of fluids at began the lab, they seemed more concerned about an upcoming volleyball match small scales is non-intuitive and enables than chemistry. However their conversation took a turn as they watched Shrinky us to manipulate bacteria in new ways. Dinks buckle, curl, and shrink in hot oil. The turning point was when one of them Working closely with graduate student began cutting funky shapes from the leftover Shrinky Dink polymer. Their attention suddenly shifted and they hypothesized about what might happen if starfish shapes, John Crooks and postdoctoral fellows shapes with bristles, or winding shapes were submerged in the oil. It was thrilling to Katie Brenner and Piercen Oliver, watch them engage and get excited about their experiments. As their unique shapes Melissa integrated microfluidics into a shrank in the oil, we discussed whether we could create a microfluidic system based segment of her chemistry curriculum. In upon these shapes, and what might happen to fluid flowing through a device. All four October 2012, John, Katie, Piercen, and of the girls were excited. I shared with them what may very well have been the only Doug spent the day in Melissa’s chemistry useful thing I said all day: that this moment of discovery is what makes science so classroom at Beaver Dam High School exciting. The experience was a reminder to me about how truly lucky I am to get to be participating in the activity with her here, every day, surrounded by sparkly, dazzling, blinking lights, studying fascinating classes. Katie summarized her experience: biological questions.

John Crooks, left, with his group of student scientists. Katie Brenner, left, with her group of student scientists.

25 Biochemistry / IPiB Degree Listings December 2010 - December 2012 Degree Name (Major Professor) Program Thesis Title

PhD Jon Mayers IPiB Roles for ESCRT-0 in Sequestering Ubiquitin Modified Cargos into Dec 2012 (Audhya) the Endosomal/Lysosomal Pathway

PhD Jae-Young Yun Biochemistry Molecular Mechanisms of Vernalization in Arabidopsis thaliana Dec 2010 (Amasino)

PhD David Zhang IPiB RNA Polymerase II Controls Transcription Dynamics Dec 2012 (Ansari)

PhD Stephen Tumasz IPiB Structural Studies of the Yeast Prp24-U6 RNA Complex Aug 2011 (Butcher)

PhD Jordan Burke IPiB The Central Role of the U2/U6 snRNA Interaction in Spliceosome Dec 2012 (Butcher) Structure and Recycling

PhD Allyson Anding Biochemistry Mechanism of 4-hydroxybenzylretinone Action in Chemotherapy Aug 2011 (Clagett-Dame)

PhD Justin Brumbaugh IPiB Application of Mass Spectrometry to Study Pluripotent Cells Dec 2011 (Coon)

PhD Marielle Gruenig IPiB RecA and its Regulators: Surprising Activities Dec 2010 (Cox)

PhD Khanh Ngo IPiB Biochemical Regulations of the Bacterial RecA Protein May 2012 (Cox)

PhD Asher Page IPiB Structural and Biochemical Studies on the Escherichia coli Dec 2012 (Cox) Protein MgsA

PhD Masaya Hayashi Biochemistry Molecular Evolution of Mitochondrial J-proteins in Yeast Dec 2010 (Craig)

PhD Alison E. Meyer Biochemistry Characterization of the Specialized role of the Ribosome-associated Aug 2009 (Craig) J-protein, Jjj1, in Ribosome Biogenesis

PhD Brittany Albaugh IPiB Mechanisms of Acetylation by the Histone Acetyltransferase- Aug 2011 (Denu) chaperone Complex Rtt109-Vps75

PhD Samuel Oliver IPiB Context Dependent Protein Interpretation of the Histone Language Jan 2012 (Denu)

PhD Michael Goren IPiB Studies on Stearoyl-CoA Desaturase and Sphingolipid Synthase May 2011 (Fox) using a Wheat Germ Translation System

PhD David Taggart Biochemistry The Baculovirus Transcriptional Regulator IE1Acts as an Origin- May 2011 (Friesen) binding Protein to Initiate Viral Genome Replication

PhD Rianna Vandergaast Biochemistry Domains that Negatively Regulate SfIAP Control Apoptosis During May 2011 (Friesen) Baculovirus Infection

PhD Justin Spanier IPiB Mechanisms of Vitamin D-Mediated Suppression of Experimental Aug 2011 (Hayes) Autoimmune Encephalomyelitis

PhD Amanda Carney IPiB The Structural and Functional Investigations of Deoxyaminosugar Aug 2011 (Holden) N,N-dimethyltransferases

PhD Nathan Bruender IPiB A Structural and Functional Investigation of Enzymes Involved in May 2012 (Holden) the Biosynthesis of D-Tetronitrose

26 Degree Name (Major Professor) Program Thesis Title

PhD Adam Courtney Biochemistry Synthetic Antigens: Mechanistic Probes of B cell Signaling Dec 2011 (Kiessling)

PhD Clinton Morgan IPiB In vivo Chemical Reprogramming of Cell Identity: Implications May 2011 (Kimble) and Applications

PhD James Ellinger IPiB Application and Development of NMR-based Metabolomics May 2012 (Markley) Techniques

PhD Gregory L. Kabachinski Biochemistry Localization and Function of Priming Factors in Vesicle Exocytosis Aug 2011 (Martin)

PhD Michelle Kielar Grevstad Biochemistry Characterization of the Spatial and Temporal Regulations of Ca2+ Dec 2012 (Martin) Evoked Vesicle Exocytosis

PhD Katie Bishop Biochemistry Mechanisms Mediating Cell- and Species-Specific Regulation of Aug 2010 (Pike) Gene Expression

PhD Paul Goetsch IPiB Integrating Components of the Vitamin D Transcriptional Dec 2012 (Pike) Regulatory Network

PhD Gregory A. Ellis Biochemistry Small Molecules to Facilitate Chemotherapeutic Delivery Dec 2011 (Raines)

PhD Michael N. Levine IPiB Applications of the Trimethyl Lock in Fluorogenic Enzyme Dec 2011 (Raines) Substrates

PhD Sean Newmister IPiB Structural Investigations of Enzymes Responsible for the Dec 2012 (Rayment) Modification of Trichothecene Mycotoxins Associated with Fusarium Head Blight

PhD Amanda Drennan IPiB Key Conformational Changes of E. coli RNA Polymerase and Aug 2012 (Record) Promoter DNA in Transcription Initiation

PhD Sara Heitkamp IPiB Characterization of Transcription Initiation Intermediates for E. Aug 2012 (Record) coli RNA Polymerase Using Fast Footprinting and Equilibrium and Stopped-flow Fluorescence

PhD Matthew Copeland IPiB The Structure and Dynamics of Flagella on Swarming Cells of May 2012 (Weibel) Escherichia coli and Proteus mirabilis

PhD Marie Foss IPiB Chemical-biological Investigation of Subcellular Organization and Aug 2012 (Weibel) Cell Division in Bacteria

PhD Ye-Jin (Jenna) Eun IPiB Development of New Physical and Chemical Tools for Studying Dec 2012 (Weibel) Microbial Physiology

PhD Hannah Tuson IPiB Bacteria-polymer Interactions: Providing Novel Insights into Dec 2012 (Weibel) Environmental Effects on Growth and Motility

MS Ashley Richie Hoggard IPiB Dec 2012 (Butcher)

MS Anli Feng IPiB May 2011 (Craig)

MS Mathangi Srinivasan IPiB May 2012 (Craig)

27 Biochemistry Advisor Degree Listings December 2010 - December 2012 Degree Name (Major Professor) Program Thesis Title

PhD Amanda C. Wollenberg CMB Genetic Exploration of the Acceleration of Flowering by Shade and Aug 2011 (Amasino) Cold Exposure in Arabidopsis thaliana

PhD Josh Tietjen MBTG Dissecting the Complexity of the CTD Code Aug 2011 (Ansari)

PhD Colleen M. McMichael CMB The Arabidopsis SCD Proteins, Putative Mediators of Clathrin Aug 2011 (Bednarek) Dependent Trafficking in Cytokinesis and Cell Expansion

PhD Audrey Klingele Microbiology Directed Evolution of Radiation Resistance in Escherichia coli: Dec 2011 (Cox) Many means to One End

PhD Jeanette K. Ducett CMB Activation of the Pleiotropic Drug Resistance Regulon by the Aug 2012 (Craig) Molecular Chaperones Ssz1 and Zuo1

PhD Lingyin Li Chemistry Synthetic Surfaces to Control Cell Fate Dec 2010 (Kiessling)

PhD Rebecca A. Splain Chemistry Synthesis of Galactofuranose-based Acceptor Substrates for the Dec 2011 (Kiessling) Study of Galactan Biosynthesis

PhD Joseph R. Klim CMB Tailored Surfaces for Investigating Human Pluripotent Stem Cells May 2012 (Kiessling)

PhD Margaret Lee Wong Chemistry Chemistry for Probing Protein-protein Interactions May 2012 (Kiessling)

PhD Shane Mangold Chemistry Synthesis and Evaluation of Quinoxalinones as Inhibitors of the Dec 2012 (Kiessling) Lectin DC-SIGN

PhD Samira Musah Chemistry Synthetic Substrata to Instruct Human Pluripotent Stem Cell Fate: Dec 2012 (Kiessling) From Novel Ligands to Functional Biomaterials

PhD Dyan E. Morgan CMB Stem Cells and Differentiation in the C. elegans Male Germline Aug 2011 (Kimble)

PhD Joshua J. Snow CMB FOG-3/Tob Can Either Promote or Inhibit Proliferation in the Aug 2011 (Kimble) Caenorhabditis elegans Germline

PhD John J. Jeong CMB Interplay Between Cell Cycle Regulators and Developmental Signals Dec 2011 (Kimble) in the Caenorhabditis elegans Germline

PhD Aaron M. Kershner CMB Control of Stem Cell self-renewal in the Caenorhabditis elegans Dec 2011 (Kimble) Germline

PhD Jason M. Peters Genetics Genome-scale Studies of rho-dependent Transcription Termination May 2012 (Landick) in Escherichia coli

PhD Kuang-Lung Hsueh Biophysics NMR Investigations of the Rieske Protein from Thermus Aug 2011 (Markley) thermophiles Support a Coupled Electron and Proton Transfer Mechanism and a Diffusion Model

PhD Jin Hae Kim Biophysics Investigation of Escherichia coli IscU, Partially-Folded Iron-Sulfur Aug 2011 (Markley) Cluster Scaffolding Protein

PhD Ziqi Dai Biophysics Studies of Conformational States of Proteins involved in Dec 2012 (Markley) Biosynthesis of Iron-Sulfur Cluster

PhD Natalia S. Morsci CMB The Role of Kinesin-like Protein 6 in Structure and Function of May 2012 (Martin) Ciliated Sensory Neurons 28 Degree Name (Major Professor) Program Thesis Title

PhD Omar N.A. Demerdash Biophysics Modeling of Protein Function at the Intra- and Inter-protein Level: Dec 2010 (Mitchell) Computational Models for Allostery Hotspot and Protein-binding Prediction

PhD Christopher M. Bianchetti Biophysics Structure and Functional Characterization of Cellulases and Their Aug 2011 (Phillips) Interactions with Cellulose

PhD Aaron N. Bryden Computer Visualization and Analysis of Protein Flexibility Dec 2011 (Phillips) Sciences

PhD Aram Chang Biophysics Enzyme Structures and Analysis of the Region Specificity in Natural Dec 2011 (Phillips) Product Biosynthesis

PhD He Zhang Biophysics Modeling Reaction-diffusion Process in Modular Biomolecular Aug 2012 (Phillips) Systems with a Lattice Monte Carlo Algorithm

PhD Amit Choudhary Biophysics n → π* Interactions in the Molecules of Life Aug 2011 (Raines)

PhD Nadia K. Sundlass Biophysics Electrostatic Interactions of Biological Processes: Cellular Dec 2011 (Raines) Internalization of Pancreatic-type Ribonucleases and Salt-bridge Formation in a DNA-wrapping Protein

PhD Sayani Chattopadhyay Chemistry Collagen Mimetic Peptides for Wound Assessment and Healing May 2012 (Raines)

PhD Michael J. Palte MCP Characterization and Exploitation of the Glycocalyx for Drug May 2012 (Raines) Delivery

PhD Benjamin R. Caes Chemistry Catalytic Systems for Carbohydrate Conversions Aug 2012 (Raines)

PhD Jacqueline J. Chritton MBTG Translational Repression by Yeast PUF Proteins In Vitro May 2011 (Wickens)

PhD Amy Cooke CMB CAF1 Deadenylases. To Deadenylate or Not: That is the Question Aug 2011 (Wickens)

PhD Yiling Yvonne Koh Microbiology RNA Recognition by the PUF Protein Family Dec 2011 (Wickens)

PhD Jacqueline Baca CMB Characterization of a Staufen Homolog in C. elegans May 2012 (Wickens)

MS Lauren Michael Biophysics Dec 2012 (Butcher)

MS Anthony Fowler Chemistry Aug 2012 (Kiessling)

MS Jack Ho Engineering Aug 2012 (Weibel)

MS Daniel Pauw CMB2 Dec 2012 (Weibel) CMB: Cellular and Molecular Biology MBTG: Microbiology Doctoral Training Program MCP: Molecular and Cellular Pharmacology 29 Postdoctoral Training Postdoctoral fellows further develop their research and teaching skills, preparing for independent positions. By Professor Robert Landick

Postdoctoral Teaching has become an increasingly social hours with invited speakers training in the attractive career option to many trainees. that this year have included talks by Department of The Department has responded by scientists from local Biotech companies, Biochemistry has creating new opportunities for training an intellectual property specialist a long and storied in teaching. Trainees have collaborated from the Wisconsin Alumni Research history, but has with faculty to develop lectures in Foundation, and the Director of the never played a the lab course, Biochemistry 651. Wisconsin Entrepreneurs' Network. more vital role Postdoctoral fellows gain teaching PALS also held a poster session and in our research experience by developing topics social hour Oct. 25 with prizes donated success than it does today. Currently for discussion, and leading seminar by BioForward, the Wisconsin chapter over 50 postdoctoral trainees conduct sections on a biochemical theme. In of the US Biotechnology Industry research in one of the lab groups led by Biochemistry 660, trainees work with Organization, helped organize a our 32 faculty. Many are supported on Professor Wickens to develop lectures on Postdoctoral Career Development research grants, but at least ten current biochemical methods for the incoming Conference held at UW-Madison April trainees are supported by individual graduate students. This approach 6, and has been active in outreach efforts postdoctoral research fellowships from a provides the experience of teaching through the UW-Madison Science variety of sources including the National a course – as many of the postdocs Expeditions group. Institutes of Health, the American ultimately will do as faculty – but in Our postdoctoral fellows are a special Cancer Society, and the Life Sciences microcosm, enabling their research to group of research scientists at a formative Research Foundation. continue unabated. For deeper training, stage in their careers. They often bring Research is the primary focus the University of Wisconsin Delta new scientific expertise and drive the of most postdoctoral fellows. Their program (www.delta.wisc.edu) offers department’s productivity; but they also scientific accomplishments are too a year-long Certification in Research, form critical links with students, faculty numerous to list, but are a cornerstone Teaching, and Learning – an outstanding and one another. This network brings in the department’s success. Each year, opportunity for those seeking a teaching irreplaceable vitality and unanticipated faculty nominate outstanding trainees career. collaborations. for the department's Boyer Award for Postdoctoral organizations New developments in postdoctoral Postdoctoral Excellence, named for coordinate professional activities training are in the works – tune in to Nobel Laureate Paul D. Boyer (see and create new opportunities. The the next newsletter for updates on those “Boyer Award” essay page 14). This UW-Madison Postdoctoral Association initiatives. If you have ideas, suggestions year’s recipient is Zachary Campbell, for the Life Sciences (PALS) (www. or want to help support our efforts, recognized for superior research biochem.wisc.edu/pals/), which began please contact Bob Landick (landick@ achievement in Professor Wickens' in Biochemistry, now is campus-wide. biochem.wisc.edu). group. PALS organizes monthly meetings/

30 IPiB Update An update on a critical driving force for excellence and sense of community -- our graduate program, IPiB. By Professor Ivan Rayment

IPiB -- the 2013. During one of three recruiting not all-work-and-no-play, some of the Integrated weekends, prospective students have entertainment at the Retreat will be Program in had an opportunity to meet with faculty presented by members of IPiB in the Biochemistry -- is to learn about their research firsthand, form of a band. Pearl Snaps is a rock the major graduate to ask questions and share stories with cover band whose members are graduate program in the IPiB student hosts, and to experience students: Paul Wrighton and Ginny department, and everything that Madison has to offer. Kincaid (both IPiB and Kiessling Group is a collaboration Current IPiB students play an active members), Andrew Reidenbach (IPiB - between role in the recruitment weekends, Pagliarini Group), and Spencer Scholz Biochemistry and Biomolecular escorting guests from their hotel to (Chemistry - Tehshik Yoon). Chemistry. As we prepare to welcome their meetings on campus, serving as our eighth incoming IPiB class this fall, a resource we will try to bring you up to date on on campus the program and its graduates. life and the The IPiB program consistently rigors of ranks among the top ten graduate the lab, and biochemistry programs in the U.S., and arranging enjoys a stellar international reputation “down time” for its ground-breaking research and activities, high-caliber students. Our first PhD such as rock degree was conferred in the Fall of 2010 climbing – only four years after IPiB accepted its and museum first graduate class. Since then, 64 PhDs haunting. and 10 MS degrees have been earned by These IPiB graduate students mentored by faculty ambassadors in Biochemistry and Biomolecular offer the best Pearl Snaps: Chemistry. The majority of our perspective to Andrew (drums), Spencer (bass) Paul (guitar) & Ginny (vocals & guitar) graduates have gone on to postdoctoral the recruits, programs. because they know first hand what it is To find out what some of our IPiB like to study and live in Madison! Are you a former member of IPiB? grads are doing with their degrees, check The program is also gearing up for its If so, please contact us (alumninews@ out the IPiB website at http://ipib.wisc. biennial Student Retreat in September biochem.wisc.edu) and let us know how edu/ipib-welcome/?page_id=27. 2013 at the recently renovated Overture being in Madison has benefited your Currently, 111 students are enrolled Center on State Street. The Retreat will current occupation. Feel free to share in the IPiB graduate program. In be a day-long opportunity for students a memory from your graduate student February and March, the departments to share their science through oral or days, or tender some advice for current of Biochemistry and Biomolecular poster presentations, possibly uncover students and you might be featured in Chemistry hosted approximately 60 new collaborative opportunities, in a our next newsletter or on our web page. students who have applied to the setting separate from the focus of work IPiB program for entry in the Fall of in the lab. To demonstrate that we are

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31 SFLC IPiB Student Faculty Liaison Committee The Student Faculty Liaison Committee, a graduate student organization, reports on its extensive work to support graduate training and serve the Biochemistry community. By Loren LaPointe Chair IPiB SFLC 2012-2013 The goals of the keep it a bi-annual event that is productive "Method of the Year" by Nature Methods, SFLC are broad, and well attended by the department. and in 2011 he also gave a TED talk. We and draw on The retreat features awards and a student are very excited to host him as our student- students, faculty speaker elected by graduate students, invited speaker! and outside among other great talks by faculty, students, Outreach. Our 2011 Outreach Chairs participants. Let us and post-docs. Joe Klim (a CMB graduate were Basu Bhattacharyya (Keck) and highlight a few of of the Kiessling Lab) was voted to speak at Erin Ronayne (Cox) and the current our recent projects the retreat in 2011, and we also had the chairs are Basu Bhattacharyya, Chrissy and innovations. pleasure of hearing an excellent talk about Petzold (Keck), and Andrew Reidenbach Foster connections between students the history of our department during (Pagliarini). They led us to: and faculty. Our social chairs work hard dinner by Prof. Dave Nelson. Darryl 2 a set of themed experiments in the to put on annual events to provide an Wesener (Kiessling) is taking charge of Wisconsin Science Festival in both 2011 opportunity for department members to planning the 2013 Biochemistry Retreat (The Central Dogma) and 2012 (Sweet socialize, network, and have a little fun (Date TBA in September 2013), which Science – the Biochemistry of Sugars). together. In 2011 Kelly Stecker (Sussman) will be held downtown at the Overture 2 participation in the Second Harvest and Shruti Waghray (Wickens) had Center. It should be very exciting and we Food Bank every year and this past October record turnout for the Halloween and hope to see everyone there! we helped sort 2000 pounds of eggs to Holiday parties and added a new tradition Invited speaker. The students of the donate to local food banks! to our annual costume and ornament department nominate a faculty member 2 volunteer at the Science Olympiad competitions: an antique centrifuge to speak here at UW-Madison. Graham at West High School on December 15th. from Prof. Dave Nelson to display as a Erwin (Ansari) has been the chair of this If you have further ideas for outreach trophy! The trophy will be recycled each committee for the past two years and activities please contact Basu, Chrissy, or year as a new lab gets bragging rights. So organized our event in October 2011 where Andrew! far, it resides in the Raines Lab. Andrew we invited Prof. David Bartell from MIT The website for SFLC has been updated Reidenbach (Pagliarini) and Ginny to give a talk on his work on microRNAs, thanks to Sean Johnston (Raines)! The site Kincaid (Kiessling) have taken the reins ~22-nucleotide transcripts that bind displays photos from our events, and Sean in 2012 as our social chairs and are in the to protein-coding genes and repress has also been providing a list of recent midst of organizing the biggest social event translation. Graham is also organizing publications from IPiB students and of the year, the Holiday Party. this year’s event, which is coming up in post-docs. Check us out at http://www. Discussion of career options. Chelcie December and we have invited Prof. Ed biochem.wisc.edu/sflc/, or link to us via Eller (Raines), who served as SFLC Chair Boyden. Prof. Boyden develops tools the IPiB website under “Current Students.” 2011-12, organized Life Sciences Career for controlling and observing dynamic On the website, you also will find all of our Day, a very successful campus-wide event for circuits of the brain, and uses these officers’ emails and upcoming events. students and post docs to get information neuro-technologies to understand how Please contact us if you have any about various career paths for science cognition and emotion arise from brain questions or would like to become more PhDs through panels of professionals as network operation. In 2010, his work involved! well as small break out sessions. Hundreds on optogenetics was recognized as the of students participated, not only from IPiB, but including Microbial IPiB students relaxing at the 2012 student picnic Sciences, Cellular and Molecular Biology, Cellular and Molecular Pathology, and others! The Biochemistry Retreat. In Fall 2011 the IPiB SFLC brought back the annual Biochemistry Retreat, headed by Justin Spanier (graduate of Hayes), with a lot of help from Khanh Ngo (graduate of Cox Lab and SFLC Chair 2010- 2011). The department hasn’t held a formal retreat in several years and we are hoping to

32 UBSO Update (Undergraduate Biochemistry Student Organization) An undergraduate organization that facilitates education, research and career planning.

UBSO functions as a community group A few things UBSO has been doing: biochemistry major. Students exchange for students interested in biochemistry Orientation: A few UBSO veterans advice on balancing courses and encourage to connect, share ideas, learn from each helped with the Freshmen Biochemistry underclassmen to utilize the excellent other, and even have some fun while Orientation program. We gave incoming professional advising services provided by doing it! UBSO is dedicated to advising its freshman a tour of the Biochemistry the biochemistry department. students as well as providing information buildings and fielded questions about the Talks by outside speakers: UBSO about job and internship opportunities organization, classes, and life on campus. helps to illuminate opportunities for through meetings and seminars. Mentoring: UBSO continued its graduates by hosting speakers from Students also have the opportunity peer mentoring program that launched medical schools, graduate schools, Teach to get involved in the community and in 2011. Upperclassmen paired with for America, and the biotechnology on campus through UBSO. Meetings freshman biochemistry students explain industry. are typically 6 pm on Wednesday nights the ins and outs of the department. The Meetings: Students in UBSO twice a month. There are no membership mentorship program also provides an benefit from learning about professional dues or requirements to become a opportunity for incoming students to ask development opportunities such as “How general member. For more information questions about time management, how to get into a Research Lab,” “Study or to be added to our email list, contact to navigate university resources, and how Abroad,” “How to Write a Research [email protected] or visit http:// to make the most of the college experience Proposal,” and many others. ubso.weebly.com/index.html. in order to ease the transition to UBSO provides a special opportunity college. for undergrads to meet and help one Advising: Each semester another, learn about the exciting research UBSO hosts a meeting going on in the department, and to think geared towards exploring the creatively about science! course requirements of the

UW-Madison Memorial Union Terrace Photo: Jeff Miller

Science IS Art Microchannels that create patterns of fluid: The Memorial Union Terrace Chair

2 mm Design: Piercen Oliver, Weibel Lab. Photo: Robin Davies Photo: Jeff Miller 33 Remembering Paul Kaesberg By Professor Paul Ahlquist Paul Kaesberg, the W.W. Beeman responsibilities was to be in charge of the become a widespread symbol for viruses. Professor of the Department of University’s first electron microscope. His Paul complemented his physical Biochemistry and Institute for Molecular X-ray scattering studies and expanding studies with a variety of biochemical Virology, passed away on December electron microscope investigations approaches, including diverse studies of 24, 2010 at the age of 87. Paul will be contributed substantially to growing RNA sequence, structure and function. widely remembered for his fundamental evidence that a large fraction of viruses In the course of these, his group advanced contributions to multiple areas of virology, produce virions with an approximately early RNA sequencing approaches based his generous mentoring of students and spherical shape. Even more importantly, on ribonuclease fragmentation. Their postdocs, and his roles in initiating some Paul used ingenious electron microscope results included the first demonstration by important institutions in the field. His direct sequencing that the amber codon colleagues will also miss his dry wit, is UAG, and early oligonucleotide-based administrative insights and other counsels, comparisons revealing closely related which all proved valuable in many sequences in certain RNA bacteriophage. situations. This latter work established an early Paul was born in Germany but foundation for the more global and emigrated at age two with his family to the sophisticated nucleic acid sequence US, settling in West Bend, Wisconsin. Paul comparisons that are now commonplace. conducted graduate studies in Physics at Later, Paul’s group published the first UW-Madison in the laboratory of William adaptation to RNA templates of Fred Beeman, where he developed X-ray Sanger’s powerful dideoxy-nucleotide- scattering methods for studying biological based DNA sequencing method, providing macromolecules. Paul completed his PhD approaches broadly useful for direct studies in 1949, and shortly afterward joined of the sequence, structure, protein binding the university faculty in Physics. In sites and other features of long RNA 1955 he transferred to the Department molecules. of Biochemistry, and remained in that In further studies of virion and viral department through the rest of his career. Paul Kaesberg with his electron microscope RNA structure and function, Paul and his In 1961, Professors Kaesberg and in the early 1950s. colleagues contributed to the recognition of Beeman founded the University’s Biophysics shadowing methods to transcend technical multicomponent, divided RNA genomes, Laboratory, which in 1966 occupied its limitations of the time, and to show an important feature in the genetics of present site in Bock Laboratories, adjacent definitively that these “spherical” virions many viruses. Paul’s group was also a to the Biochemistry Department. Paul possessed icosahedral symmetry (see figure pioneer in using E. coli and eukaryotic chaired the laboratory from 1969 through from Science article). Such symmetry is in vitro translation systems to study viral 1988, the longest serving chair to date. In now recognized as such a nearly universal RNA coding capacity and expression 1987, under his guidance, the laboratory principle of isometric virion structure mechanisms. Among other findings, their name was changed to the Institute for and assembly that the icosahedron has results revealed the strong general tendency Molecular Virology to reflect the evolution of eukaryotes to efficiently translate only the Structure of Small of its research directions. "Spherical" Viruses most 5’-proximal open reading frames in Early in his research career, Paul began Paul Kaesberg mRNAs. As part of this work, Paul’s group to turn his attention to viruses as sources (1956) Science 124: mapped and sequenced the first ribosome of uniform biological complexes that 626-628 binding site from a eukaryotic mRNA, could be purified for physical studies. His revealing its close linkage to the 5’ end. He subsequent research was characterized by a and his coworkers also demonstrated that series of breakthroughs so fundamental to in eukaryotic systems, downstream open virology that present students can hardly reading frames in a mRNA are generally imagine a time when these cornerstones not translated, but become translatable of the field were not known. Prominent when their initiation codon is linked to examples include some of his early insights the 5’ end by 5’-truncation of the mRNA. from physical studies on the structure of In the course of his studies, Paul infectious virion particles. Such virions were worked with many different viruses, known to be nucleoprotein complexes, but always choosing for each research question their organization was uncertain. Paul’s Fig. 2a (left). Electron micrographs of heavily one or more agents best suited to the early small angle X-ray scattering studies shadowed turnip yellow mosaic virus. Because of particular biological issues and technical were the first to demonstrate that such the heavy shadowing and high contrast printing, the demands of the problem. Accordingly, particles consisted of an outer protein shell particle contours are much distorted; however, the particle shadows should be clearly delineated. (x about his papers featured in aggregate a large with the nucleic acid on the inside. 150,000.) Fig. 2b (right). Icosahedral models of the variety of bacterial, plant and animal One of Paul’s initial faculty particles of Fig. 2a. viruses. Nevertheless, in nearly all cases, 34 American Society Queen and royal family, and culminated for Virology. with a formal procession through the He was also a central streets of Leiden by the honorees, charter member Leiden University officials and faculty, of the Biophysical representatives of many other prominent Society. In 1963 world universities, and government he obtained a officials. With all faculty in full academic lifetime NIH robes representing the many colors of their Career Award that disciplines and universities, the procession paid much of his traveled to the presentation hall cheered salary throughout by thousands of spectators and trumpet his career. fanfare from adjacent roofs. O n e Paul’s many interests evolved through particularly his life and in later years included memorable cosmology and bridge. A continuing recognition for passion was UW basketball. Paul was a Paul and his season ticket holder for over 60 years and Paul in 1987-88 with models depicting progressively more complex family was his attended a Badger basketball game less virion structures with icosahedral symmetry. receipt in 1975 of than two weeks before his unexpected and an honorary Doctorate of Science from the peaceful passing. A devoted family man, the principles revealed by Paul’s work have University of Leiden in the Netherlands. Paul is survived by Marian, his wife of 57 proven broadly relevant to a wide range of This honor was magnified because it years, his three sons Paul, James and Peter, virus-host systems. was one of 13 honorary degrees specially two grandchildren, and many grateful Among other honors, Paul was a awarded on the 400-year anniversary students and postdocs. The memory of his member of the National Academy of of that University’s founding, an event accomplishments, humor and generosity Sciences, a Fellow of the American intimately linked with the history of Leiden will long be treasured by numerous Academy of Microbiology, and a charter and The Netherlands. The elaborate week- colleagues around the world. member and President (1987-88) of the long festivities included meetings with the

As we went to press W.W. "Mo" Cleland passes away The Department has voted to dedicate its next international Steenbock Symposium to Mo, with a focus on enzymology. A full memorial essay will appear in our next Newsletter. A description of the Steenbock Symosium to be held in his honor appears on page 47. A Fund has been established at the University of Wisconsin Foundation to honor Mo Cleland's contributions to the Department of Biochemistry (fund number 12157778). Although the exact use of these funds is yet to be defined, it is planned that they will reflect his great generosity of time towards graduate students and postdocs.

"Dithiothreitol: a new protective reagent for SH groups". Cleland, W. W. (1964) Biochemistry 3: 480-482

Mo Cleland died on March 6, 2013 as a result of injuries sustained in a tragic accident. Mo was a giant in enzymology. Among his many contributions was bringing about order to the field of multi-substrate kinetics and developing novel methods to examine enzyme mechanisms. He demonstrated the use of diothiothreitol – now commonly known as Cleland’s Reagent – as an antioxidant in protein purification and stabilization. Mo loved sailing on Lake Mendota, was a devotee of the Madison Symphony and Opera, and a serious and a nationally recognized philatelist. He was generous to colleagues and collaborators, and a Reduction of a typical disulfide bond by Dithiothreitol (DTT) aka Cleland's reagent via two sequential thiol-disulfide dominant force in mechanistic enzymology and in our department. exchange reactions.

35 In Memoriam: Masayasu Nomura Adapted from David Tennenbaum and Millard Susman Departments, later as a member of the Institute of Enzyme Research. Millard Susman, a past Chairman of UW Genetics (now retired), was hired in the same year as Nomura, 1963. “After his arrival in Madison,” Susman says, “he decided that although the ribosome field was very competitive and he wanted to avoid the rat race, he found they were irresistible, so he entered the field, and became Mr. Ribosome. He and his grad students deciphered the mechanism Normura while at UW-Madison that allows the ribosome to make proteins, Normura in 2009 visiting UW-Madison Masayasu Nomura, a molecular taking exact instruction from the genes.” fantastic ability to see what needed to be biologist and professor of Biochemistry and “We occupied neighboring labs in done, and do beautiful experiments to push Genetics at UW-Madison between 1963 genetics and had daily contact,” Susman knowledge forward, and kept going and and 1984, passed away on Nov. 19 of 2011, adds. “He’d talk about what was going on, kept going. I have huge respect for him, as at age 84 in California. and I would feel appropriately inadequate. a scientist and a person who was extremely Nomura’s scientific focus was the He was really doing earth-shattering generous and supportive of me when I was ribosome, a structure in the cell of all research.” a young scientist.” organisms that, under genetic control, “He was one of the most incredibly Susman says Nomura, who emigrated assembles the proteins necessary for cellular skilled and influential scientists, but he from Japan after World War II, was chemistry and structure. never got as much credit as he deserved,” “extremely hard working, he spent hours Using techniques that would be says Richard Burgess, a professor emeritus and hours reading the literature, and considered primitive today, Nomura of oncology, who collaborated on several was amazingly brilliant at finding ways performed the amazing feat of papers with Nomura. “He just had a to answer scientific questions. He was disassembling and reassembling the small a magical laboratory worker, and his subunit of the ribosome in a test tube. He productivity was just amazing. If he had discovered how mutations in this machine been more assertive, he probably would could make bacteria resistant to antibiotics, have won a Nobel Prize.” and dissected the pathways by which cells Bill Reznikoff, a former Biochemistry control growth through formation of faculty member, remembers Masayasu proteins and RNA in ribosomes. as a quiet but warm person. “At first, I Nomura received his bachelor’s and wondered whether he was too reserved doctoral degrees from the University of to teach undergraduates. Nevertheless, I Tokyo in the years when Japan was still asked him to give a lecture/demonstration emerging from the privations of World in an undergraduate laboratory course War II, and he thought he was destined in molecular genetics. It was a magical to spend his life in hardscrabble labs experience – both for the students and for working on projects related to agriculture me. He set up an experiment with his own or pharmacology, but his curiosity, hands and walked the students through the scholarliness and bench smarts led to the question being asked and the techniques opportunity to visit the United States in used and then solicited their input in 1957 as a 30-year-old postdoctoral student. Figure 6. Revised assembly map of interpreting the results. It was a model During a three-year sojourn in the U.S., Escherichia coli 30 S ribosomal proteins...... in how to educate young students to be Nomura worked with three towering image from: scientists.” figures in the burgeoning field of molecular "Assembly Mapping of 30 S Ribosomal While at UW, Masayasu helped biology: Sol Spiegelman, Jim Watson and Proteins from Escherichia coli". W.A. Held, nucleate a “Ribosome Group,” which Seymour Benzer. He came to Madison in the B. Ballou, S. Mizushima and M. Nomura included Julian Davies, a Biochemistry 60’s to join the Genetics and Biochemistry (1974) Journal of Biological Chemistry. 249: continued, bottom next page 3103-3111. The Rosetta Stone “Nomura’s “Assembly Map”, which provided the instructions to assemble the 30S ribosome, was the Rosetta Stone for over 30 years. It was stunning that all the information needed to assemble the ribosome was present in the molecules themselves, and that the ribosome could spontaneously assemble. The question remained as to whether the process Nomura observed in the test tube was the same in a cell. Recent work has confirmed that this is indeed the case, but it is a testament to Nomura’s pioneering research that it took over three decades of technological advances to make this leap.” -- Jamie Williamson (Scripps Institute)

36 In Memoriam: Chris Raetz By Professor Dave Nelson Chris proponent of careful genetics and rigorous good writing. Raetz, a enzymology. He set very high standards for He was a member his students and his colleagues, and he lived member of of the UW by these high standards. the editorial Biochemistry Chris left Wisconsin in 1987 to take a board of the Department position with Merck Research Laboratories, Journal of from 1974- where he eventually became executive vice Biological 1987, died president for research in biochemistry and Chemistry much too microbiology. In 1993 he accepted the chair and associate young, of of Biochemistry at Duke University, where editor of anaplastic he remained until his death. During the years the Annual thyroid at Duke, Chris extended his study of lipid Reviews of cancer, on August 16, 2011. Chris was biosynthetic enzymes to the crystallographic Biochemistry. Chris Raetz while at UW-Madison born in 1946 in East Berlin, the child of determination of their structures. He also The more two industrial chemists who emigrated to made major contributions to the analysis than 30 graduate students and 40 post- Ohio when Chris was a boy. He attended of lipids and synthetic intermediates by docs that Chris trained will carry on his Yale University, majoring in chemistry, mass spectrometry. When a consortium tradition of good genetics coupled with then did his M.D. and Ph.D. work at the led by Ed Dennis of UCSD began the good enzymology and critical thinking. But Harvard Medical School. In his Ph.D. effort to determine the complete lipidome it won’t be the same without him. research in the laboratory of Eugene P. of a mammalian cell, Kennedy, he extended Kennedy’s work on Chris took a major the synthetic pathways to phospholipids role in that project. of the E. coli membrane, using thorough Chris’s exceptional enzymology and very hard work. He spent qualities as a scientist a post-doctoral year with Herbert Tabor at were recognized with the NIH, then joined UW Biochemistry in the ASBMB’s Avanti 1974. Award in Lipids While at the UW Chris began a long (in 2002), the van series of genetic and biochemical studies Deenen Medal from that led eventually to the elucidation of the the University of entire ten-step pathway for the synthesis of Utrecht (2006), and lipid A, the core of the lipopolysaccharide his election to the endotoxin of E. coli and other Gram- National Academy negative bacteria. This (the Raetz pathway) of Science (2006), and related problems occupied most of his among other honors. attention for the rest of his career. He was Chris produced Figure 2. Constitutive pathway for biosynthesis of the Kdo2-lipid more than 300 papers A portion of LPS in E. coli K-12 ...... image from: a generous and supportive colleague, an "Lipid A Modification Systems in Gram-Negative Bacteria" enthusiastic teacher of undergraduates and that were models of C.R.H. Raetz, C.M. Reynolds, M.S. Trent, and R.E. Bishop (2007) mentor of graduate students, and a strong careful science and Annual Review of Biochemistry 76: 295-329.

Nomura continued faculty member. Julian recalls that it seemed Nomura continued to work on ribosomes, Academy of Arts and Sciences, and the unimaginable that Masayasu had succeeded but he turned from bacteria to yeast. He Danish Academy of Arts and Sciences. in taking apart a ribosome and putting it continued to be a major force in ribosome In 2002, he received the Abbott-ASM back together again. He notes that “The research and was active in research until the Lifetime Achievement Award from the fact that Masayasu was not awarded a very end, discovering that the molecular American Society for Microbiology. Nobel Prize was a great injustice to one of genetics of yeast ribosomes was significantly Basic biology still benefits from the best scientists I have ever met.” different from that of bacteria and rejoicing Nomura’s insights, Susman says. “Nomura In 1984, eager to live near more at all the surprises that he encountered. showed that the 22 pieces of a ribosomal Japanese-Americans, the Nomuras moved At both universities, Nomura mentored sub-unit could be put into a test tube and, to California, where Nomura became generations of graduate and postdoctoral under the right conditions, they would just the Grace Bell Professor of Biological students. Nomura was much honored. glom together into a working structure. Chemistry at the University of California- He was elected to the National Academy It was as if you put a bunch of gears and Irvine. of Sciences, the American Academy of springs in a box, gave it a shake, and opened Madison lost something irreplaceable Arts and Sciences, the American Academy it to find that they had come together into a when Nomura moved away. At Irvine, of Microbiology, the Royal Netherlands working cuckoo clock. Amazing.” 37 In Memoriam: Har Gobind Khorana Adapted from Aseem Z. Ansari, Marsha Rich Rosner, and Julius Adler (Cell, 147. 12/23/11) world, but has been singularly profound Institute for Enzyme Research, a vanguard in India. There, Gobind symbolizes of chemical biology at UW-Madison. the fact that education and talent can UW and MIT. From 1960 to 1970, overcome socioeconomic and intellectual Gobind was a member of our Department, boundaries. and Co-Director of the ‘‘Enzyme Institute’. Gobind began his education under a During this period, he generated and tree in a small village of a hundred families, amplified synthetic oligonucleotides. who were mostly illiterate. Fortunately, Using the oligonucleotide CUCUCU, his talent was recognized early, and he he discovered that the triplets CUC and went on to Punjab University in Lahore. UCU encode the amino acids leucine and Although he almost became an English a serine, respectively. Marshall Nirenberg major, he graduated with a Masters in had previously shown that UUU encoded Chemistry and then won a rare fellowship phenylalanine, and Gobind, with to pursue a Ph.D. in organic chemistry at characteristic humility, always noted that the University of Liverpool in England. Nirenberg’s work inspired his own. After obtaining his doctorate in 1948, Gobind enthusiastically moved to Eidgenössische Technische Hochschule (ETH) in Zurich to join the group of Vladimir Prelog, a chemist who won a Gobind Khorana with Julius & David Adler Nobel Prize in 1975. In less than a year, in 1966 while at UW-Madison Biochemistry he had to leave Zurich because his savings Gobind Khorana traversed boundaries, ran out. During his brief tenure at the both scientific and cultural. He pioneered ETH, however, Gobind serendipitously the use of chemistry and physics to encountered the little known work of answer fundamental questions in biology. Fritz Zetzsche on carbodiimides, which In particular, he helped decipher how later was crucial in Gobind’s synthesis of RNA encodes protein, and how light is nucleotide cofactors and ATP. perceived. His research earned him the Gobind failed to find a position in Khorana with Nirenberg during the Nobel Prize in Medicine in 1968. Although India, but then received a three-year 2009 Steenbock Symposium deeply modest and unassuming, Gobind fellowship with Alexander Todd at would often remark, ‘‘I only work on big Cambridge University. There, Gobind Gobind next set his sights on problems.’’ Indeed, only such challenges learned of Sanger’s exciting advances in synthesizing a complete gene. Ultimately, were worthy of Gobind’s extraordinary protein sequencing, Perutz’s and Kendrew’s he synthesized the coding and regulatory intensity, creativity, and focus. breakthroughs in protein crystallography, regions of a tRNA gene, and demonstrated Gobind is an icon for science sans and Todd’s own work on nucleic acids. This that it worked in bacteria. This tour de force frontiers. He was an early practitioner of innovative environment drew Gobind, a defined a framework for biotechnology what is now known as Chemical Biology. synthetic organic chemist, to the newborn and, 40 years later, is still used to assemble He pioneered new synthetic routes for field of Molecular Biology. synthetic genes and genomes. nucleotide cofactors and oligonucleotides In 1952, Gobind began his independent The second phase of Gobind’s career and then used these synthetic molecules scientific career as a nonacademic began after he left Madison for MIT. There, to help elucidate the genetic code. He researcher at the British Columbia he focused on the mechanism by which assembled the first synthetic gene, laying Research Council in Vancouver, Canada. intrinsic membrane proteins function the foundation for Synthetic Genomes His seminal scientific contributions can be and how they interact with phospholipids and Synthetic Biology. In 1971, after he grouped into two phases. The first focused in the lipid bilayer. His interests led him joined MIT, he described the amplification on nucleotides and nucleic acids, using to bacteriorhodopsin and, eventually, of synthetic genes in a series of enzymatic carbodiimides to form pyrophosphate mammalian rhodopsin. steps. 15 years later, these were enhanced bonds, which eventually led to the first The strategy he chose was a forerunner with a thermostable DNA polymerase, and synthesis of coenzyme A and ATP. Soon, of contemporary systems biology: sequence became PCR. At MIT, Gobind took on Gobind wrote to Van Potter, a leading the protein, mutate every residue, express lipids and membrane proteins, focusing on cancer biologist at UW-Madison, asking and reconstitute the proteins in a native rhodopsins until his retirement in 2007. if he would test his synthetic ATP in biological context, and then meticulously From India to UW. The elegance of rigorous biochemical assays. Van Potter monitor the phenotypic perturbations. Gobind’s work has inspired generations not only obliged with the experiments, but Gobind and his co-workers elucidated how of chemists and biologists around the also succeeded in bringing Gobind to the bacteriorhodopsin, and latter mammalian

38 rhodopsin, pumps protons across the membrane when activated by light. The Khorana program. Inspired by Gobind’s story, UW-Madison launched the Khorana Scholars Program. This program places American and Indian students in leading laboratories in the other country, for a transformative summer research experience (see the article on page 20 of this newsletter). In 2007, the year Gobind retired from active research, Gobind generously lent his name to the program. During his last visit to UW-Madison, Gobind met the 2009 scholars. His joy at Masayasu Nomura and Hikoya Hayatsu with Gobind Khorana meeting the future generation of scientists during the 2009 Steenbock Symposium and their passion for science was palpable. Symposia,’’ which were held in various His beloved wife Esther, whom he lost in parts of the world. The last such gathering 2001, ensured that he was free to focus was in 2009 at the 33rd Steenbock exclusively on science. Gobind tragically symposium on Synthetic Gene to Synthetic lost his daughter Emily in 1978 but is Genomes. Many of the scientists that survived by his loving children David and spoke, in describing their current work, Julia, who cared for him in his final years. noted how Gobind shaped their thinking Har Gobind Khorana pursued his work and how his contributions continue with a single-minded intensity but to propel new fields, such as synthetic remained humble to the end. His innate and chemical biology. As a tribute to curiosity and appreciation of life (as well Gobind, UW-Madison has made these as that quick laugh, that slight tilt as he talks publicly accessible at http://www. craned his head to listen, and that quizzical biochem.wisc.edu/seminars/ steenbock/ look) will remain with those who were Khorana with Khorana students 2009 Steenbock Symposium symposium33. fortunate to be his friend. In a collection A devoted family. Gobind had a deep of his papers published a decade ago, he The respect and warmth felt by interest in nature and its beauty; he actively quoted from Otto Loewi, who could have Gobind’s academic family was readily sought solitude in natural settings to describing Gobind himself: ‘‘We must be evident in the periodic ‘‘Khorana think deeply and critically about science. modest except in our aims.’’

Table of contents from The Journal of Molecular Biology Vol 72 Issue 2 December 28, 1972

The entire Journal was devoted to papers authored with Khorana

(as well as the first two in the next issue)

39 Honors & Awards Faculty Rick Amasino 2011 American Association for the Advancement of Science Fellow Aseem Ansari 2011 Romnes Faculty Fellowship 2012 Keck Foundation Grant Sebastian Bednarek 2011 Vilas Associate Award Mike Cox 2011 American Association for the Advancement of Science Fellow Paul Friesen 2012 American Society for Virology Lifetime Membership Award Colleen Hayes 2012 Scientific Researcher Award, National Multiple Sclerosis Society Hazel Holden 2011 Kellett Award Laura Kiessling 2011 WARF Named Professorship 2012 Murry Goodman Memorial Prize 2012 ACS Claude S. Hudson Award Judith Kimble 2012 Elected to serve on National Medal of Science Award Comm. James Ntambi 2012 FASBMB Teaching Award 2012 Elected to serve on AAS IOM Food and Nutrition Board

Dave Pagliarini 2011 Glenn Award 2011 Searle Scholar 2011 Ellison Medical Foundation New Scholar Award (declined) 2012 Shaw Scientist Award Ann Palmenberg 2012 American Society for Virology has created 2 "Ann Palmenberg Junior Investigator Awards" to be given annually in her honor Wes Pike 2012 Louis V. Avioli Award Recipient 2012 Career Award for Vitamin D Research George Phillips 2012 American Association for the Advancement of Science Fellow Ron Raines 2012 Finalist in Inaugural WARF Innovation Awards 2012 Chicago Clean Energy Challenge Award John Ralph 2012 Fulbright Grant 2012 Stanford’s GCEP (Global Climate and Energy Program) Distinguished Lecturer Award Ivan Rayment 2012 WARF Named Professorship Mike Sussman 2012 Named Bascom Professor Doug Weibel 2012 NIH New Innovator Award 2012 Gates Foundation Grand Challenges Grant Marv Wickens 2011 Elected to American Academy of Arts and Sciences

Staff

Dan Barnish Dept. Office 2012 Excellence in Higher Education Award Mark Meyer Pike 2012 ASBMR Young Investigator Award 2012 Vitamin D Workshop Travel Award Yuki Tobimatsu Ralph 2012 Best Research Poster Award Plant Cell Wall Gordon Research Conference 2012 ASPB Robert Rabson Award

40 Postdoctoral Staff Lars Renner Weibel 2011 Paul Boyer Postdoctoral Excellence Award Zak Campbell Wickens 2012 Paul Boyer Postdoctoral Excellence Award Postdoctoral Fellowships 2011 J. Kyle Friend Kimble American Cancer Society Thomas Ream Amasino Life Science Research Foundation Chen-Yu Wang Attie American Diabetes Association Mentor Based Fellowship Zachary Campbell Wickens NIH Ruth L. Kirschstein National Research Service Award Paul Grimsrud Pagliarini NIH Ruth L. Kirschstein National Research Service Award Matthew Kotlajich Landick NIH Ruth L. Kirschstein National Research Service Award Nicholas McGrath Raines NIH Ruth L. Kirschstein National Research Service Award Langdon Martin Raines NIH Ruth L. Kirschstein National Research Service Award Jamie Verheyden Kimble NIH Ruth L. Kirschstein National Research Service Award Tonya Zeczycki Cleland NIH Ruth L. Kirschstein National Research Service Award 2012 Sarah Brenner Weibel Hartwell Posdoctoral Fellowship Matthew Bruss Attie Trainee on the Molecular and Applied Nutrition T. G. J. Kyle Friend Kimble American Cancer Society Thomas Ream Amasino Life Science Research Foundation Hannah Seidel Kimble Life Science Research Foundation Scott Aoki Kimble NIH Ruth L. Kirschstein National Research Service Award Zachary Campbell Wickens NIH Ruth L. Kirschstein National Research Service Award Kevin Desai Raines NIH Ruth L. Kirschstein National Research Service Award Paul Grimsrud Pagliarini NIH Ruth L. Kirschstein National Research Service Award Matthew Kotlajich Landick NIH Ruth L. Kirschstein National Research Service Award Matthew Kraft Kiessling NIH Ruth L. Kirschstein National Research Service Award Nicholas McGrath Raines NIH Ruth L. Kirschstein National Research Service Award Jamie Verheyden Kimble NIH Ruth L. Kirschstein National Research Service Award Tonya Zeczycki Cleland NIH Ruth L. Kirschstein National Research Service Award

Graduate Students 2011 Brittany Albaugh Denu 2011 IPiB Graduate Teaching Excellence Award Matthew Copeland Weibel 2011 IPiB Graduate Mentoring Award Michael Goren Fox 2011 Sigrid Liermo Memorial Award in Biochemistry Angela Gruber Cox 2011 Keystone Symposia Travel Scholarship Audrey Klingele Cox 2011 Graduate School Vilas Travel Award Matt Mead Hull 2011 Travel Award Jonathan Mitchell Friesen 2011 American Society for Microbiology Student Travel Award Asher Page Cox 2011 Graduate School Vilas Travel Award Asher Page Cox 2011 Vilas Research Travel Award 2012 Ben Knowles Record 2012 IPiB Graduate Teaching Excellence Award Hannah Tuson Weibel 2012 IPiB Graduate Mentoring Award Kelly Hoadley Manthei Keck 2012 Sigrid Liermo Memorial Award in Biochemistry Nathaniel Byers Friesen 2012 American Society for Virology Student Travel Award Ben Knowles Record 2012 Gordon Biopolymers Conference Graduate Best Poster Maggie Strable Ntambi 2012 Cell Metabolism Oral Presentation Award Josue Baeza Denu 2011-2012 Biological Scholars Award Michael Bellecourt Landick 2011-2012 Biological Scholars Award Lucas O’Neill Ntambi 2011-2012 Biological Scholars Award Ian Windsor Raines 2011-2012 Biological Scholars Award Matthew Zmudka Holden 2011-2012 Biological Scholars Award

41 Honors & Awards continued Graduate Students Graduate Fellowships 2011 Nathan Bruender Holden CALS Wisconsin Distinguished Graduate Fellowship Matthew Copeland Wiebel WARF Scholar James Ellinger Markley Sam C. Smith Graduate Fellowship Ye Jin (Jenna) Eun Weibel Senator Robert Caldwell Graduate Fellowship Award Amy Jancewicx Rayment 2010-2011 Advanced Opportunity Fellow Sean Johnston Raines Autism Speaks Fellowship Douglas Knowles Record Arnold & Catherine Denton Graduate Fellowship Christopher Lapointe Wickens Biochemistry WARF Research Assistant Award Khanh Van Ngo Cox Genentech Graduate Research Fellowship Juan Rodriguez-Molina Ansari Jerome Stefaniak Graduate Fellowship Sohel Shamsuzzaman Pike Ahmad Scholar Rebecca Phillips Rayment NSF Graduate Research Fellow Johnnie Walker Fox NSF Graduate Research Fellow Darryl Wesener Kiessling NSF Graduate Research Fellow Jordan Burke Butcher Wisconsin Distinguished Graduate Fellowship Sean Newmister Rayment Wisconsin Distinguished Graduate Fellowship Asher Page Cox Wisconsin Distinguished Graduate Fellowship 2012 Justin Acheson Fox CALS Wisconsin Distinguished Graduate Fellowship Joshua Carson Pagliarini American Heart Association Fellowship Joseph Esquibel Martin 2011-2012 Advanced Opportunity Fellow Sean Johnston Raines Autism Speaks Fellowship Douglas Knowles Record Denton Fellowship Christopher Lapointe Wickens Genentech Graduate Fellow Manohary Rajendram Weibel Mao Wisconsin Distinguished Graduate Fellowship Hillary St. John Pike DeLuca Fellowship in Biochemistry Jonathan Stefely Pagliarini NIH Ruth L. Kirschstein National Research Service Award Johnnie Walker Fox NSF Predoctoral Fellowship Josue Baeze Denu NSF Graduate Research Fellow Virginia Kincaid Kiessling NSF Graduate Research Fellow Corey Nemic Ansari NSF Graduate Research Fellow Chrissy Petzold Keck NSF Graduate Research Fellow Rebecca Phillips Rayment NSF Graduate Research Fellow Erin Ronayne Cox NSF Graduate Research Fellow Kelly Stecker Sussman NSF Graduate Research Fellow Amelia Still Pagliarini NSF Graduate Research Fellow Darryl Wesener Kiessling NSF Graduate Research Fellow Kate Helmich Ralph WARF Research Assistant Grad Fellow Loren LaPointe Senes WARF Research Assistant Grad Fellow Training Grant Awards 2011 Nathaniel Byers Friesen Trainee on the Madison NIH Virology T. G. Matt Mead Hull Microbes in Health and Disease T. G. Benjamin Mueller Senes Computation and Information in Biology and Medicine T. G. Maggie Strable Ntambi Trainee on the Molecular and Applied Nutrition T. G. Robert Presler Raines Trainee on the Biotechnology T. G. Elena Sorokin Kimble Trainee on the Biotechnology T. G. Kristen Andersen Raines Trainee on the Chemical Biology Interface T. G. Christine Bradford Raines Trainee on the Chemical Biology Interface T. G. Darryl Wesener Kiessling Trainee on the Chemical Biology Interface T. G. Lauren Michael Butcher Predoctoral Trainee on Molecular Biophysics T. G. Johnnie Walker Fox Predoctoral Trainee on Molecular Biophysics T. G. Jordan Burke Butcher Trainee on the Molecular Biosciences T. G. Lindsay Hoover Craig Trainee on the Molecular Biosciences T. G. Angela Manlick Cox Trainee on the Molecular Biosciences T. G. Jonathan Mitchell Friesen Trainee on the Molecular Biosciences T. G. Katherine Rank Rayment Trainee on the Molecular Biosciences T. G. Erin Ronayne Cox Trainee on the Molecular Biosciences T. G. 42 Training Grant Awards continued James Vasta Raines Trainee on the Molecular Biosciences T. G. Paul Wrighton Kiessling Trainee on the Molecular Biosciences T. G. Kristen Andersen Raines Trainee on the Molecular and Cellular Pharmacology T. G Alex Carlson Pike Trainee on the Molecular and Cellular Pharmacology T. G. Neil Daily Martin Trainee on the Molecular and Cellular Pharmacology T. G. 2012 Christine Bradford Raines Trainee on the Chemical Biology Interface T. G. Nathaniel Byers Friesen Trainee on the Madison NIH Virology T. G. Matt Mead Hull Microbes in Health and Disease T. G. Benjamin Mueller Senes Computation and Information in Biology and Medicine T. G. Juan Rodriquez-Molina Ansari Trainee on the Genomic Sciences T. G. Tucker Carrocci Hoskins Trainee on the Biotechnology T. G. Robert Newberry Raines Trainee on the Biotechnology T. G. Douglas Porter Kimble/Wickens Trainee on the Biotechnology T. G. Robert Presler Raines Trainee on the Biotechnology T. G. Jan Windsor Raines Trainee on the Biotechnology T. G. Jordan Burke Butcher Trainee on the Molecular Biosciences T. G. Angela Manlick Cox Trainee on the Molecular Biosciences T. G. Paul Wrighton Kiessling Trainee on the Molecular Biosciences T. G. Rachel Barkley Rayment Trainee on the Molecular Biosciences T. G. Michael Bellecourt Landick Trainee on the Molecular Biosciences T. G. Laura Bond Ntambi Trainee on the Molecular Biosciences T. G. Trish Hoang Raines Trainee on the Molecular Biosciences T. G. Sean Johnston Raines Trainee on the Molecular Biosciences T. G. Molly McDevitt Pagliarini Trainee on the Molecular Biosciences T. G. Jonathan Mitchell Friesen Trainee on the Molecular Biosciences T. G. Lucas O’Neill Ntambi Trainee on the Molecular Biosciences T. G. Jarred Renvold Pagliarini Trainee on the Molecular Biosciences T. G. Katharine Schulz Harrison Trainee on the Molecular Biosciences T. G. James Vasta Raines Trainee on the Molecular Biosciences T. G. Kelly Werner Pagliarini Trainee on the Molecular Biosciences T. G. Brendan Floyd Pagliarini Trainee on the Molecular and Applied Nutrition T. G. Maggie Strable Ntambi Trainee on the Molecular and Applied Nutrition T. G.

Undergraduate Majors 2011 Hilldale Undergraduate Research Fellowship: 2012 Hilldale Undergraduate Research Fellowship: Grant Barber (Pagliarini) Lauren Buckley Amy Davis (Raines) Lauren Hoffer Zeeshan Haq (Record) Ian Johnson Brandon Hernandez (Kiessling) Amy Yan Athavi Jeezanathan Michael Kerins (Record) Austin Krejci (Pagliarini) Benjamin Knight (Mitchell) Mark Kraemer (Record) Michael Montenero Kellie Kolb (Landick) Joel Prince (Raines) Katherine Omernick Nathan Menninga (Adler) Sonia Trevino-Dopatka (Weibel) Brian Rekoske Ryan Sacotte (Weibel) Sang Joon Won (Cox) Christopher Schmitz Yuliang Leon Sun (Hoskins) Michael Voss (Landick) 2011 ASM Undergraduate Research Fellowship: L&S Honors Program Research Scholarship Sonia Trevino-Dopatka (Weibel) : Alison Huckenpahler (Record) 2011 University Book Store Academic Excellence Awards: Dana Bellissimo (Record) Desmond Chan Trewartha and Mark Mensink Senior Thesis Award: 2011 Undergraduate Nucleic Acids Best Poster Award in Wenting Cai (Mitchell) the Research Poster Competition ASBMB Annual Meeting: Khorana Program Fellowship: Joseph Piechura (Cox) Athavi Jeevananthan (Pagliarini)

SCORE Program Fellowship: Grant Barber (Pagliarini)

43 Great Lakes Bioenergy Research Center A cross-campus center for innovative research to produce fuel from biomass includes four Biochemistry faculty. By Professor Rick Amasino The Greatserve on the management team: Rick efforts is the discovery of how to use ionic Lakes Bioenergy Amasino, Brian Fox, Bob Landick, and liquids in the break down of biomass into Research Center John Ralph. sugars without the need for enzymes or (GLBRC) was In addition to working in the area of pretreatment steps. This work was done in founded in 2008 improving plant biomass, I serve as the Ron Raines’ group, and resulted in Ron with the support management team member representing founding the first start-up company based of the Department our education and outreach efforts. on GLBRC research. The company, called of Energy (DOE). Our center has devoted a portion of Hyrax Energy (http://hyraxenergy.com), There are two our funding to educating the public won the 2012 Clean Energy Challenge other such centers, about energy issues. Two of my GLBRC sponsored by the Clean Energy Trust of the Joint BioEnergy Institute (jbei. colleagues, John Greenler and Leith Nye, Chicago. org) in the San Francisco Bay Area, work full time on education and outreach, This year the Wisconsin Energy and the BioEnergy Science Center and we collaborate with other education Institute (WEI) building opened. The (bioenergycenter.org) headquartered in experts such as Hedi Baxter-Lauffer (UW) WEI, which is located east of the Enzyme Oak Ridge. This year the DOE renewed and Charles “Andy” Anderson (MSU). Institute on the corner where University all three Bioenergy Research Centers at Our efforts include developing classroom Avenue and Campus Drive meet, is a the same rate of funding as in the previous materials and conducting workshops campus-wide “meta-center” that will 5-year award – $25 million total costs per for K-12 teachers in the use of these bring together many energy-related efforts year for 5 years. The goal of these centers materials, summer research programs for in research, education and service. It is is to perform basic research that will undergraduates that focus on minorities distinct from, but will interface with, enable the production of transportation and students from small colleges, and the GLBRC. Areas of focus in the WEI fuels from biomass. developing computer games that educate include: liquid fuels for transportation Our center is headquartered at in the area of energy in collaboration systems; thermal and electrical energy University of Wisconsin-Madison and our with a group at the Wisconsin Institute storage and utilization; carbon neutral major partner is Michigan State University. for Discovery (http://discovery.wisc.edu/ electricity; policy, economics and societal The lead PI for the center is Tim Donohue, home/wisconsin/research/education- impact of energy challenges; and energy a professor in the Bacteriology Department research/). You can peruse many of outreach and service programs. You at the UW and our Chief Scientific our materials at http://www.glbrc.org/ can read about the WEI at http://www. Officer is Ken Keegstra, a professor in education/. energy.wisc.edu. My GLBRC colleagues the Department of Biochemistry & Presently, most of the ethanol used in in education and outreach will move into Molecular Biology at MSU. Tim and fuel comes from corn grain because the the first floor of the building to become Ken are joined on a management team starch in corn grain is readily converted part of a larger educational effort, and by nine faculty members from UW and to sugar. In biomass, most of the sugar John Ralph will move his research group MSU who represent the four scientific that one hopes to utilize is in cell walls— into beautifully designed lab space in an areas of the center: 1) improving plant structures that have, for obvious reasons, upper research floor. biomass, 2) deconstructing biomass, 3) evolved to be quite resistant to breakdown. We look forward to another 5 converting biomass to energy, and 4) The goal of the deconstructing biomass years of working in the important area fostering sustainable bioenergy practices. area is to break down biomass into sugars of sustainable, carbon-neutral fuel (Descriptions of the four research areas in an efficient and economical manner production. Follow our progress at are at http://www.biochem.wisc.edu/ which is a major challenge in converting http://www.glbrc.org. newsletters/2008/glbrc.aspx). biomass into liquid fuels. One highlight Four Biochemistry faculty currently from the Center’s deconstructing biomass

44 From the Emeritus Faculty My great interest by means of biochemistry and genetics to Another approach to this same subject is to find out get at the mechanism involved here, with is to study mutants we ourselves have what is in charge hope to ultimately expand this knowledge isolated. Normal flies avoid going to of an organism to all other organisms including people. an attractant mixed with overpowering (if anything!). I Some thirty mutants (obtained from repellent. The undergraduates here have pick my research Martin Heisenberg, Roland Strauss, and found mutants that can't decide what to projects to try to Douglas Armstrong) are now known that do ("Towards finding out how a decision get an answer to are defective somewhere in the fruit fly's gets made: The response of Drosophila to that. central complex but the nature of the conflicting stimuli and the isolation and Julius Adler In charge of a defect in each is not yet known. Eight study of decision mutants", manuscript person and of other primates appears to be undergraduates and I are trying to find about to be submitted). Also, normal flies the prefrontal cortex. That was discovered that out. We have shown that five of these run away from repellents and go instead about 40 years ago by Aleksandr Luria. thirty are defective in sending a message to attractants. The undergraduates have In fruit flies the analog of the prefrontal to the fly's legs and wings. These are the found mutants that don't know what to cortex seems to be the central complex. ones we study to find out how "thinking" do ("Drosophila mutants that are motile We study the fruit fly's central complex is translated into "action". but fail to respond to any sensory stimuli", manuscript about to be submitted). The defect in each of these mutants will be discovered in order to learn how the central complex functions. The above thoughts are included in the figure at left. Recently one of my postdoc heroes (1979!) returned to Madison to visit me, Marty Springer. We enjoyed Babcock chocolate hot fudge sundaes. The same will be provided to any of you, please come. Oops! also chocolate sundaes went to visitors Joe and Maddie Sanfilippo, now graduate students at Indiana.

Research in the includes one of the capstone projects research program as Assistant Professor Perry Frey Group in Madison and continuing research in of Chemistry at Clark University in continues on a Taiwan. Worchester, MA. Phil Schwartz recently smaller scale with Perry resigned as Associate Editor of moved from Pfizer Research to Takeda departmental Biochemistry after 20 years of service. California in San Diego. Kafryn Lieder support for supplies He resigned his last Editorial Board operates The Well Tempered Word, on two capstone membership with Bioorganic Chemistry, LLC in Madison. Dawei Chen is in projects. Dawei after 25 years of service. Perry also resigned transition while exploring small business Chen is working as a member of the Advisory Council to opportunities in Madison. Perry Frey part-time on these the Redox Biology Center at the University In retirement, Perry is pursuing a new projects, with the additional assistance of of Nebraska after 12 years of service. He challenge. Never having learned music in Laurie Reinhardt of the Cleland group, derived satisfaction in these roles but felt his youth, he decided to learn music in while pursuing other interests. Positive that it would be best to make way for his “second childhood” as a student of the initial results on either project would younger scientists. Perry has continued piano. After taking lessons for three years, represent significant progress. Perry to review research papers and has recently he now regards himself as an intermediate continues to collaborate with Professor written Perspective and Review articles for student of the piano, with aspirations to Shyue-Chu Ke at the National Dong Hwa publication. become as proficient as a typical teenaged University, Taiwan on the characterization Wisconsin alumni of the Frey group student. He might reach that level within of free radical species at the active site of are in transition at academic institutions two or three years. This activity keeps him lysine 5,6-aminomutase. The most recent and companies. Glen Hinckley moved occupied many afternoons and evenings, advance has led to the identification of from Elmhurst College to Farmingdale year-round. It gives him great pleasure. a third radical generated from lysine State College, SUNY. Kuo-Hsiang analogues. The collaborative research Joseph Tang is developing his productive

45 The Reznikoff pseudo retirement: own. We were again in Uganda a year ago How long will I continue to do it? I am In writing this and had a wonderful and rewarding time. considering three more years if my health short report from a I am the Director of Education and also allows. Professor Emeritus of Housing and Conferences at the MBL. Speaking of health (and we are in pretty (merit = deserve, I thought that I was retiring from writing good shape), one problem with aging is e = out; therefore I grant proposals but now I do it almost that you discover lots of little things that deserve to be out) continually – but it is worth it. Because the are not quite functioning at an optimal I want to thank students that I meet who take our research level – like my right knee that doesn’t like Marv for asking immersion courses come away with me to bicycle. But they are small. me to write this career changing I am really sorry to hear that Mo has Bill Reznikoff document. experiences. In died. He was an amazing institution in the Cathy and I doing the same things between the grant Department. He did not like molecular that we described before – only more so. proposals I try biology (until he had to accept the title in Cathy has a real passion for working with to help course order to pick up a student with molecular a Ugandan NGO that serves a whole slum directors arrange biology training grant support) but he community with a school, a clinic, a credit their courses and could be really entertaining and if one union, etc. Thank you James Ntambi for I have to deal needed a volunteer to help undergraduates, introducing us to Uganda and for helping with all sorts of he was right there to do it (although what us, particularly Cathy, in our efforts. little problems. “it” was, was not quite clear). Too bad too These efforts include donations of shoes, It keeps me sad. clothing, computers, etc. that James’ study busy and out abroad program takes to Uganda; and of trouble. Give us a call if you happen to come to financial donations that we send on our Rez returns to his youthful hangout - MBL Cape Cod. We would love to see you.

couldn’t imagine leaving in Oneida county. Headquarters is a two- our neighborhood where bedroom cottage which includes a garage there are no such houses. so that in Rhinelander I do not have to We found the south- scrape snow and ice from my Subaru. On facing kitchen she “always the other hand I have a lot more snow wanted” with a sun room shoveling to do in the front yard. That is overlooking a sheltered actually fortunate because, except for pine back yard perfect for birds pruning, I don’t do much forest work in and other loveable critters. the winter. First, because heavy winter Ruth loves puttering in clothing taxes my stamina as I grow “her” garden which is fine older and second because of a wolf pack with me as I love to putter prowling in my vicinity intimidates me. in “my” woodlands. She Paul DeLong, Wisconsin’s chief forester has converted the basement assures me there is no record of a wolf into a potting center and attacking a human but that provides him laundry. So, as we enter greater assurance behind his desk than our eighty years of life, we it does me when I am alone in the deep Roland Ruckert Splitting birch logs still live in a two-story with snow. basement and attic and a single garage But I digress from my forest manager It’s been 16 years since I retired from with my Subaru still facing ice and snow activities. Our woodland is 310 acres of academia and reinvented myself as a forest every winter. And we can still walk to mixed conifer and hardwood growing manager. Marv Wickens suggests it’s time Trader Joes, our bank, pharmacy, library in poor to good soil, undulating glacial for a progress report. First, we moved two and perhaps most importantly, the Laurel till presenting a variety of biomes. One years ago, after 43 years on West Lawn Tavern. Oh, the house is tight, warm and hundred acres I inherited from my Ave., to Fox Ave two blocks away. Ruth requires one-third the amount of energy father; the rest we acquired over the years “hated” the north-facing kitchen and to heat and air condition. beginning when I was a student in 1957. leaky windows. I had imagined we’d find Meanwhile I spend half my life in our Since my retirement at the end of 1996 a single story house with a double garage woodlands, a 3 ½ hour drive north to I have been learning how to manage it. where I could shelter my Subaru from 2374 Rueckert Road, about 5 miles, as Management, in this case, doesn’t mean the elements during the winter. Ruth the crow flies, southeast of Rhinelander planting trees. It is more a matter of 46 selecting “desirable” trees by removing shears and pruning shears, as the case I alluded above to wolves. These those less so. In the hills and eskers I favor may be. Bucking the trees into segments, woodlands are also inhabited by deer, bear, long-lived white and red pine and oak at splitting them and piling the firewood coyotes, bobcat, raccoons, mink, ferret, the expense of short-lived balsam fir which is invigorating in the dry cool fall, but beaver, muskrats and just recently, I’m grow like grass but make lovely aromatic sweaty and disagreeable during the humid assured by locals, by cougar and moose. Christmas trees. The wet lowlands are mosquito season. I also work on esthetics, As for flora I have so far catalogued 142 dominated by sedge marshes which, the keeping brush from taking over on trails. species, some of which are coveted enough biologist say, have been that way since the But the heavy lifting of forest management to merit visits by a local nursery which has last glaciers receded. The drier lowlands is done, not by me, but by a logger. I have, cloned some of them. are dominated by spruce, fir and tamarack in the last fifteen years had five harvests; Finally I should mention that we whose roots can survive the anaerobic soil each has been overseen by a DNR (Dept put our woodland under a permanent conditions. of Natural Resources) state forester. His conservation easement with the When the trails are clear of snow much services are paid by a 5% state tax imposed Northwoods Land Trust a few years ago. of my time is occupied by keeping the on the harvest. I have been fortunate in They monitor the land each year to insure roads cleared of fallen timber, my source selection of my logger, Dennis Schoeneck it is being managed to their standards. If of firewood. I patrol my three miles who happens to be a neighbor, and who you are visiting the northwoods, be sure to of logging trails on a sturdy all-terrain this year was selected Wisconsin State Tree stop by and visit. I’d be happy to show you vehicle (ATV) carrying necessary tools - Farmer of the Year. After each harvest the what I am doing. 2374 Rueckert Road, chain saw, pole saw, pruning saw, lopping woods looks healthier. Rhinelander WI 54501 (715) 362-4324

Steenbock Symposium on Enzyme Structure and Function will be held at The University of Wisconsin-Madison, May 22-24, 2014. This symposium is hosted by the Department of Biochemistry, and is in honor of the life of W. W. Cleland, our colleague and friend. The symposium will bring together leading scientists in the field to discuss their most recent research activities, and how they have been influenced by Professor Cleland’s remarkable contributions to enzyme chemistry. The speaker list includes: Karen Allen – Boston University Richard Armstrong – Vanderbilt University Vahe Bandarian – University of Arizona John Blanchard – Albert Einstein College of Medicine Squire Booker – Penn State University Debbie Dunaway-Mariano – University of New Mexico Paul Fitzpatrick – Texas A&M Judith Klinman – University of California – Berkeley Tom Meek – GlaxoSmithKline Frank Raushel – Texas A&M Nigel Richards – Indiana University – Purdue University, Indianapolis Vern Schramm – Albert Einstein College of Medicine JoAnne Stubbe – MIT Wilfred van der Donk – University of Illinois Grover Waldrop – Louisiana State University Session chairs include: Perry Frey – University of Wisconsin Rowena Matthews – University of Michigan Dexter Northrup – University of Wisconsin George Reed – University of Wisconsin Peter Tipton – University of Missouri Chris Walsh – Harvard University The banquet talk will be given by Professor Paul Cook from the University of Oklahoma, who will tell us about another side of Mo – namely his stamp collecting activities. The symposium promises to be both a great scientific experience as well as a chance for friends to come together to celebrate the life of our “mechanistic hero.” Organizers for the symposium are Debbie Dunaway- Mariano, Hazel Holden, Frank Raushel, Ivan Rayment, and Nigel Richards.

47 From the Labs Calling all Past Members of the Department of Biochemistry We want to hear from you!!!! Let us know what you have been up to. Please remind us of the faculty or facility you worked with and approximately when. Send updates to: E-mail: [email protected] or regular mail in care of the department. Keep in touch!! Like the Department on Facebook facebook.com/UWMadisonIPiB

Greetings from the even more exciting follow up paper in 2013. Andrew Lang, Preston Easterday, Hong Butcher Lab! 2012 Jordan successfully defended her thesis, did Hong Liao and Alex Blume. Andrew and was a busy and a brief postdoc in NMRFAM and then Preston have graduated and Andrew is a exciting year for us. moved on to UCSF where she is a postdoc medical student at UW-Madison. Preston We purchased the with Hiten Madhani. Katie Mouzakis is currently in the process of applying to department’s first produced another research highlight for medical school. Hong Hong continues to small angle X-ray us by investigating the mechanism of be an energetic and enthusiastic researcher. scattering (SAXS) ribosomal frameshifting in HIV. This work Alex got off to a strong start and is currently instrument, was recently published in Nucleic Acids studying abroad in Sweden. Butcher lab which allows us Research. Katie defended her Ph.D. and is Finally, we welcomed the newest to determine the low-resolution shapes gearing up to move to beautiful Durango, members of the Butcher Lab, Allison of macromolecules in solution. This CO where she has accepted a tenure-track Didychuck and Eric Montemayor. Allison instrument is now housed in NMRFAM position as an Assistant Professor at Fort is a very bright first year biophysics graduate and has been very popular. Jordan Burke Lewis College. student. Eric is an outstanding postdoc demonstrated the power of a combined Ashley Hoggard and Lauren Michael from the University of Texas Health SAXS and NMR approach by solving graduated this year with Master’s degrees. Sciences Center at San Antonio and will the structure of a complex of U2 and U6 Ashley gave birth to Albert Elmer Hoggard, split his time between our group and David spliceosomal RNAs. These RNAs are major a healthy boy born this year on July 18th. Brow’s group in Biomolecular Chemistry. components of the spliceosome active site, Lauren is working on campus at the Center Both Allison and Eric will be working on and among the largest RNA structures ever for High-Throughput Computing. the spliceosome project, our long-standing determined in the solution state. Check out We’ve had an awesome team of collaboration with Dave Brow. her 2012 paper in RNA, and look for an undergrads working in the lab this past year:

Some time after the scientist Laurie Reinhardt and Mo again with Richard Wolfenden at North Carolina following letter was hosted our collaborators, John Wallace at Chapel Hill and it’s always a pleasure to written, on March and Paul Attwood from Australia, Sarawut see and work with him. He is collaborating 6th 2013 Mo “Yui” Jitrapadkee from Thailand and with scientist Mark Anderson on the Cleland passed away. former Rayment post-doc, Martin St. kinetic isotopes effects of the reactions of Mark and I will Maurice from Milwaukee. We discussed enzymes maleamate amidohydrolase and always remember our individual results and planned future 6-hydroxynicotinate 3-monooxygenase. Mo fondly for his experiments for our pyruvate carboxylase Mark and Brian Smith (Denu Lab) mentorship and his project. It’s always an intense, productive, published their work on nicotinamidase. Cleland lab great generosity in and enjoyable few days. In addition to Mark is continuing their work on Sir2. sharing his vast knowledge with others. We the pyruvate carboxylate project, Laurie Anna Rutkowski is an undergraduate who will also miss stopping in his office to hear a is continuing to study the mechanism now works with Mark on these projects. story about some past escapade, the storyline of the reaction of NAD+ Synthetase (M. Tania Soerianto, an undergraduate from an opera or old movie he just watched, or tuberculosis) and its mutants. working with Laurie, was awarded a paid some advice on just about anything. Mo lived In the summer we warmly welcomed internship at Nostrum Laboratories Inc. his life doing what he loved to do everyday. Professor John Marlier from Cal Poly again in Kansas City, Missouri for the summer to come and perform research in our lab. 2012. She graduates in May 2013. In January, Mo attended and spoke He is working on his project about thioester There’s good job news concerning at the Isotopes in Chemistry and Biology hydrolysis funded by NSF with co-principal Tonya! In July, Tonya started as an assistant GRC held again in Galveston, Texas. In investigators Dr. Kristen Meisenheimer, professor at the school of medicine of East December, Mo joined a family gathering Emily Fogle, and Lori Robbins. Carolina University in Greenville, North for Christmas in California. Afterward, he In addition to John, Associate Professor Carolina. She is in the Department of attended the 23th Enzyme Mechanisms Mark Snider from the College of Wooster Biochemistry and Molecular Biology. Ann Conference held in Coronado Bay, in Ohio came to our lab to perform Menefee, who completed her Ph. D. (’09) California in early January 1013. research this summer. We’ve known Mark with George Reed, has joined her lab as a In June post-doc Tonya Zeczycki, since he was a graduate student (Ph. D ’01) post-doc/lab manager. 48 Hi all, All are from B.P. Konstanitov Petersburg the University of Aberdeen, Scotland in It has been a big Nuclear Physics Institute, Department December 2011. year here. Perhaps of Molecular and Radiation Biophysics, Joseph Piechura received a 2011 most important, National Research Centre “Kurchataov Nucleic Acids Best Poster Award in the I have recovered Institute”, St. Petersburg, Russia. Undergraduate Student Research Poster almost completely Competition at the ASBMB Annual from my very scary Arrivals: Meeting in Washington, D.C. 2011 bout with Stefanie Hartman Guillain Barre Chen joined the lab in Cox lab Syndrome. I had November 2012 as a a 6 month sabbatical in the first half of postdoc. She received 2012, and used it in part to complete the her B.S. at Virginia Tech 6th edition of the Lehninger text. That text in 2005 and her Ph.D. was printed just before Thanksgiving. We at Duke University in have some very interesting initiatives going 2012. Her thesis advisor in the lab, and I am looking forward to an was Dr. Tao Hsieh. exciting 2013. I miss you all and hope you are all in store for a happy and healthy year Goings: Mike had dinner with a few Cox lab alums (Khanh Ngo, Xiao-hong to come. Audrey Klingele, Qian, Sarita Jain, Leslie Waite and Qun Shan) in Albany, CA, summer 2012. Warmest regards, Mike Khanh Ngo and Asher Page all received PhDs. Audrey is now Past Lab News: More News: working at Lucigen. Khanh is a postdoc at Sarita Jain sent news that she September 2012 Rose Byrne was UCSF – Mission Bay in the lab of Maria joined XenoPort as Senior Director, selected to participate in the ASBMB Public Barna. Asher plans to join the Michael Eck Business Development. XenoPort is a Affairs Advisory Committee’s sponsored lab at the Dana-Farber Cancer Institute in biopharmaceutical company focused on Fall Student Hill Day in Washington early 2013. developing therapeutics for the treatment D.C. During this time, students and Charles Dulberger left the lab in July of nervous system disorders, including postdocs from around the country come 2011 to pursue graduate school at the neuropathic pain, spasticity and Parkinson’s to Washington D.C. to meet with their University of Chicago in the fall. He’s now disease. own congressional representatives to at University of Chicago in the Molecular Lisa Iype sent news that she’s working describe their research and advocate for Biosciences cluster, Biochemistry & for the Institute for Systems Biology in NIH funding. Rose met with Elizabeth Molecular Biophysics. Seattle as a Bioinformatics Scientist. Swartz of Senator Ron Johnson’s office and Cédric Norais sent news from France Representative Rehberg of Montana. Awards: that he’s enjoying teaching biology to (http://asbmbpolicy.wordpress. Mike Cox was elected to the rank of engineering students and is doing research com/2012/09/14/a-busy-week-for- AAAS Fellow. on the E. coli CRISPR system. asbmbs-public-affairs-office/) Erin Ronayne received the 2012 Lukas Bane is now a graduate student National Science Foundation Graduate and has joined Dr. Rachelle Gaudet’s September-October 2012 Dmitry Research Award. lab at Harvard and has been working on Baytin, Irina Bakhlanova and Alexandra Asher Page received the 2011-2012 determining the structure of an integral Dudkina arrived in Madison to work in the Wisconsin Distinguished Graduate membrane divalent metal transporter. Cox lab on an ongoing collaboration that Fellowship Award. Joseph Piechura is now a grad student initially began with Dr. Vladislav Lanzov. Angela Gruber received the 2011 and has joined the Dr. Erin O’Shea lab at All three previously travelled to Madison to Keystone Symposia Travel Scholarship Harvard. He’s exploring signal integration work in the lab as part of that collaboration. to attend the “DNA Replication and into the cyanobacterial circadian clock. Recombination” meeting in Keystone, Colorado. Engagements: Asher Page and Audrey Asher Page and Rachel Fried became Klingele both received engaged the October weekend immediately a 2011 Graduate School following Asher’s defense. Vilas Travel Award to attend the same meeting. Weddings: Asher Page also Angela Manlick and Ben Gruber were received a Vilas married 9/24/11, Marielle Gruenig and Research Travel Award Falk Eichhorn were married 10/1/11, Mike and Beth Cox had a party at their home in May 2012 and Qun and April 2012 Vessela Petrova and Luke Shan, Xiao-hong Qian and Brian Webb came to help celebrate Mike’s to work in the lab of birthday along with current lab members Erin Ronayne and Liz Wood. Dr. Peter McGlynn at Ensberg were married. 49 Babies: girl (Fiona Maya Eichhorn). Dongwook Kim). Akiko Sakai sent us news from Japan On August 18, 2012, Dennis Harris November 2012, Julie Eggington that she and her husband, Ryo Sakasai, had and Yeajin Song had a baby girl (Naleigh McLachlan and Adam McLachlan had a a baby girl (Chihiro). Ann Song). baby boy (Michael Robert McLachlan). On July 14, 2012, Marielle Gruenig- On October 18, 2012, TaeJin Kim and Eichhorn and Falk Eichhorn had a baby his wife, Yejoong, had a baby boy (Ethan

Greetings from the whose interest in evolution helped lead year as a visiting professor, two visiting Craig Lab. Much the Craig lab in that exciting direction has students (Julia Majewska and Michal has happened since returned to Japan for his postdoc. Rogaczewski) will arrive in March for a the last dispatch Several postdocs are off to new places year to continue their work on our joint from the lab. and new jobs. Takashi Higurashi joined Fe-S cluster biogenesis projects. Many comings the Biotech company EVEC in Sapporo, Brenda Schilke (master geneticist and goings, and Japan, a move which had the added benefit and molecular biologist) continues to many babies. We of being in the same city that his wife had bridge all the mitochondria projects, from welcomed six Craig a job! June Pais moved to Boston. As a Fe-S cluster biogenesis to mitochondrial Craig lab Lab newborns over postdoc at New England Biolabs she is import. IPiB grad student See-Yeun Ting a 16 month period, as well as Betty’s new in enzymology heaven (no, we don’t get has joined the import project. Brenda and grand-child! ! A record?? Congrats to the a discount on enzymes). Justin Hines is See-Yeun make a good team working to lab’s new parents: Amy, June, Sanjith, now an assistant professor of chemistry understand the amazing complexities of Jeanette, Hyun-Young and Ji-Yoon. at Lafayette College in Pennsylvania, the mitochondrial import motor. keeping up his interest in yeast prions. Amy Prunuske moved north, leaving THE NEWS: Chandan Sahi, who claims to greatly miss the ribosome-associated chaperones and The big news is that after working half- the Wisconsin winters, joined the faculty pleiotropic drug resistance behind, and has time for two years Willy Walter really did of the Indian Institute of Technology, settled into her new job as assistant prof retire. For his retirement party many lab Bhopal. in the University of Minnesota-Duluth alums sent their memories and amusing Ji-Yoon Song has returned to Seoul; Medical School. Lindsey Hoover and anecdotes that made us all laugh. Tom both she and her husband snagged coveted Peter Kuhn and a new (as of Jan 2012) Ziegelhoffer joined the lab (again) taking jobs at the Samsung Advanced Institute of IPiB graduate student Kanghyun Lee now over many of Willy’s roles and jumping Technology. Her Fe-S cluster/proteolysis form the core of the ribosome-associated into the world of cytosolic J-proteins, project (how is it and why is it that Isu’s chaperone group (aka “B” group). Sanjith along with Hyun Young Yu. half-life can vary from 15 min to two Yeruva has also left the lab, returning to Two PhD students graduated. hours) has been picked up by Szymon India. But Om Shrestha who joined the Jeanette Ducett (nee Waltner) moved on Ciesielski, who recently joined the lab lab (and “B” group) in 2012 continues the from the world of “what does a ribosome- as a postdoc from Gdansk, Poland. Our same enthusiasm for structure that Sanjith associated chaperone do when it's not on University of Gdansk connections remain and Jeanette brought to the lab – so the the ribosome” to the world of “real prions” strong. Not only does Jarek Marszalek Craig lab’s baby steps in that direction will (not those yeast ones). Masaya Hayashi come to the lab for several months each hopefully continue!

Hello from 141B Ryan Aschenbrener, Malak Benslimane, biofuels enzymes and their reactions and Biochemistry Connor Harmann, Albert Kim, Amy structures. Chris, Mike, Kirk and Shishir Addition and Lim, Ben Prom, Sung-Soo Kim, joined the lab since my last newsletter 4th floor of Old Cameron Seiser, and Taylor Tigue. contribution. Chris is a crystallographer Genetics. Justin is solving structures of toluene who trained with George Phillips on This updates monooxygenase and other proteins. cellulase structure and function. Mike is from 2010 to During his graduate career, he solved an enzymologist who trained with John present. structures of product bound states, has the Lipscomb in Minnesota. He is an expert In the first crystal structure of toluene bound in on oxygenases. Kirk is a bioinformatics/ Fox lab Biochemistry the active site of a diiron enzyme, solved enzymologist who trained with Sam Addition, the current people, sorted the structure of the reductase, and also the Butcher. Shishir is a chemical engineer by their lab bay south to north are hydroxylase-ferredoxin complex at 2 Å who trained with Bruce Dale at Michigan Johnnie Walker, Taichi Takasuka, resolution. Justin is not afraid of shaking, State. Combined with the protein Justin Acheson, Lai Bergeman, Chris baking, slicing or dicing any protein in engineering, biochemistry, and molecular Bianchetti, Mike Mbughuni, Kirk order to get to structure. biological skills provided by Johnnie, Vander Meulen and Shishir Chundawat. Johnnie, Taichi, Lai, Chris, Mike, Taichi and Lai, this is a really strong, The undergraduates working in the lab are Kirk and Shishir are working on various diversely talented research team. We have 50 been working on engineered cellulases George Phillips, as PI). Collectively, we (formerly UW Medical Microbiology from thermophilic bacteria and the natural make sure that University of Wisconsin and Immunology, now SUNY Buffalo), enzyme system produced by a Streptomyces maintains their decade-long contributions Arnie Ruoho, Baron Chanda and Cynthia isolated by Cameron Currie’s group from to the Protein Structure Initiative. The Czajkowski (UW Neurosciences), a microbe/insect symbiotic culture. Seems current CESG crew includes Dave Aceti, Alessandro Senes (UW Biochemistry), that wood wasps intentionally inoculate a Emily Beebe, Craig Bingman, Don and Celia Goulding (UC Irvine). We highly cellulolytic mixture of microbes and Drott, Ronnie Frederick, Andy Geisor, have membrane proteins in crystallization fungi into the pine tree when they lay their Kashia Gromek, Shin-Ichi Makino, screening trials and our project Scientific eggs. This microbial community degrades John Primm, Donna Troestler, and Advisory Board meeting is coming in the wood, contributing to the invasive Russell Wrobel. The undergraduates a month or so. It is an exciting time, as nature of the insect attack. We have working in CESG are Marley Crews-Hill, we are learning many new things about found a number of interesting enzymes Alexander Decleene, Aidan Holmes, membrane protein structure and function. that contribute to this natural destructive Jo Holder, Otto Kletzien, Jessica Liu, I have been Director of the UW capability, solved some crystal structures Hannah Meddaugh, Kylie Moyer, Trang Biotechnology Training Program since of new enzymes, and have begun to Nguyen, Kayla Olson, Rachel Schwanz, 2008, and hear about the exciting understand the basis of their function in and Fabian Suchy. research of graduate students from four the microbial community. TMPC is a collaborative project. of the colleges on campus. I still teach In the Old Genetics building, CESG We identify researchers with interesting Biochemistry 625 every spring, with transformed itself into PSI:Biology membrane proteins that can provide special guest lectures from Mo Cleland include the Transmembrane Protein biological and functional insights, and then and George Reed coming this spring. Center (TMPC, myself as PI) and the TMPC discovers how to make the proteins To you, the reader of these brief Mitochondrial Protein Partnership (MPP, for collaborative studies on structure and comments, best wishes for the coming John Markley and Dave Pagliarini as PI function. Some of our collaborators year. Please stop into the lab if you are in and Co-Investigator) and from Houston, that you may recognize include Katrina Madison for a visit. We would be happy the Natural Products Partnership (NPP, Forest (UW Bacteriology), Jay Bangs to see you.

Greetings to all! I visited with at the annual meeting of Research (NIH). Mike Guy is postdoc I hope that this the American Society for Virology. These at the University of Rochester-Medical newsletter findsvirologists include Rianna Vandergaast Center (New York) and Dave Taggart is everyone in good (IPiB) - a postdoc at the University of a postdoc at Ohio State University – the health and happy. Maryland, Nadine Dalrymple (IPiB) school that took the Big Ten Tournament The PDF lab is - a postdoc at Stony Brook University basketball title away from our Badgers still functioning (New York), and Kim Schultz (CMB) - this year! I also hear from Diccon Fiore well from the 7th a postdoc at Johns Hopkins University. and Melinda Brady-Osborne, who were Floor of R.M. Bock Doug LaCount (Biochemistry) is also our faithful research specialists in the lab. Friesen lab Laboratories. We a regular ASVer – he is professor at Just last summer, Kathy Zuehlke (Hajek) remain one of five research groups of the Purdue University and recently received visited the lab as she attended the 50th Institute for Molecular Virology (IMV) tenure there – congratulations! Another Anniversary Celebration of the CMB here at U.W.-Madison. Our main research very recent visitor to the lab was Susan Program here. Kathy is an award-winning interest continues to be the biochemistry Mendrysa, who with her two young boys science teacher in the greater Atlanta area. of host-virus interactions by using stopped by to say hello on their way to Lastly, I look forward to Steve Pullen’s baculoviruses as a model system. We focus visit grandparents near Green Bay. Susan Christmas card every year – Steve is a primarily on the virus-mediated events is a professor at Purdue and as you know longtime Senior Principal Scientist at that trigger apoptosis in baculovirus- is also married to Doug. In other alumni Boehringer-Ingelheim (Connecticut). infected cells. Most recently that interest news, Erica Lannan (MDTP) is now an Among current PDF lab members, has led us into a study of the host DNA assistant professor at Prairie State College Nate Byers (IPiB) won a position on the damage response. We have discovered that (near Chicago) and Becky Cerio (MDTP) U.W.-Madison Virology Training Grant not only do baculoviruses induce the DNA recently accepted a job in the Office of and Jonathan Mitchell (IPiB) just finished damage response in their host but they also Scientific Program and Policy Analysis his stay on the Molecular Biosciences encode genes that modulate the response at the National Institute of Diabetes and Training Grant. Nate is working on to enhance and expedite aspects of virus Digestive and Kidney Diseases at NIH. baculovirus IAPs and DNA damage. He’ll replication. How viruses manipulate the Erik Settles (MDTP) is a new Senior give his first talk at ASV this summer. host DNA damage response is a hot topic Scientist at Pan Genome Systems here in It was Jonathan who made the recent in virology of late. Madison. Duy Tran is an IRTA Fellow of discovery that our virus both induces and I have heard from many past members Developmental Glycobiology at National manipulates the DNA damage response. of our research group, several of whom Institute of Dental and Craniofacial He recently accepted a postdoc position

51 with the Lemon group (working on HCV) designer. Our crew of Brittany spaniels I am happy to report that Ann recovered at North Carolina University. Jonathan is at home is now up to three – they keep in time for the meeting and is still doing working on his thesis now – and he already us busy with healthy walks, hunting, well – our combined efforts made the has writing cramps! and canoeing on the Wisconsin River on 2012 Madison meeting one of the best Anna and I are doing well. I was weekends. In between, I have also taken up ever with respect to record attendance recently elected as Chair of the IMV so the marksman’s game of skeet. In addition (more than 1,500 virologists all in one my administrative duties have increased. to organizing charity competitions for the building), income earned for the Society In addition, I am the principal instructor American Cancer Society and the Multiple (student travel grants), extraordinary and administrator for U.W.’s only Sclerosis Society, I have even won several science, quality Madison brews served, undergraduate virology course (Biochem/ WI State championships – who would and most important – plenty of fun! Just MMI 575). With about 100 students in have thought? ask someone about “Virolympics”! this information-packed course, I keep Another labor of love for me has been It was good to see old friends at ASV busy meeting with students who want serving as local host and organizer of – it seems like half of the virologists in the letters of recommendation for medical the ASV meeting when it is held here in world have trained or worked in Madison school and students who think I will tell Madison (Monona Terrace Convention at one time or another. Consequently, one them what will be on the next exam. In Center) every five years. I was commander of the highlights of the Madison meeting reality, I enjoy the teaching and especially and chief at the 25th Anniversary Meeting is always the Badger reunion, wherein all the interaction with those students who of the ASV in 2006 and took over the virologists connected to Wisconsin share love virology. Anna continues teaching 31st annual meeting this past summer for beer, brats, and stories. Hope to see you classes in Pilates and Zumba all the while our infamous local host Ann Palmenberg, there sometime. working at the flower shop as a floral who had serious health problems last year. Until then, God Bless.

The KiesslingGrant. Additionally, Samira Musah along the way. The trip epitomized what Group has been received a Graduate Peer Mentor Award the Kiessling Group is all about: working as busy as ever the from the University of Wisconsin. hard, going with the flow (literally in past two years, Travelling the globe to share recent this case), and collaboration with good publishing a total results from the lab and promote the company. of eleven papers benefits of working at the interface of In lab news, Team Sugar continues to do between the five chemistry and biology has kept Laura sweet science. Sadly, Matthew Levengood project teams busy. Excitingly, Laura co-chaired the first and Kenzo Yamatsugu finished their ( Chemotaxis, ever Keystone Symposium on Chemical postdoctoral training. Matt has taken Kiessling lab Sugar, Stem Cell Biology, entitled “Chemical Biology and a position at Seattle Genetics, and he Lounge, B Cell Bombers, and Multivalency). Novel Tools in Pharmacology”. Several and wife, Sheeny, recently welcomed a While performing this innovative and members of the Kiessling Group, as well as beautiful baby girl to their family. Kenzo collaborative research, we still managed to other UW-Madison faculty, attended the is the newest faculty member in the have lots of fun along the way. Santa Fe conference. Everyone, including Department of Chemistry at the University Kiessling Group members have Laura, found their way to the dance floor of Tokyo. Helping to lead Team Sugar received numerous prestigious awards at the end of the meeting to celebrate is Matthew Kraft, our newest postdoc. since publication of the last newsletter. the successful and highly impactful Matt has already gained renown for his For outstanding contributions in the gathering. To stay informed about exciting skills in the lab and in science writing, field of carbohydrate chemistry, Laura opportunities like this and innovations in winning an NIH Postdoctoral Fellowship. Kiessling received the Hudson Award, the the field of chemical biology, join Laura’s With the departure of graduate students highest honor given by the carbohydrate 1000+ Twitter followers (www.twitter. Christopher Brown and Becca Splain division of the American Chemical com/chemicalbiology). there were large shoes to fill on Team Society. Laura was also recognized for her Back in beautiful Wisconsin, the Sugar. Graduate students Valerie Winton, exceptional communication skills in the Kiessling Group has not been letting Virginia Kincaid, and Philip Calabretta classroom by winning the James W. Taylor Laura have all the fun. This past summer, have accepted the challenge. With Darryl Excellence in Teaching Award. Kiessling the entire lab spent the day paddling down Wesener and Mario Martinez passing Group graduate students have received the mighty and majestic Wisconsin River. their prelims and becoming dissertators, significant recognition for excellence as Inspired by her days on the water at MIT, Team Sugar is posed to maintain its sugar well: Darryl Wesener, Nitasha Bennet, Laura and daughter Kyra quickly jumped high. Valerie Winton, and Virginia Kincaid to an early lead and headed the pack. In the Stem Cell Lounge, love is in the were awarded NSF Graduate Research Though it was quite hot and several scary air! Lab alum Lingyin Li got married Fellowships while Heather Hodges and spiders were encountered, everyone safely over the summer, while current students Joshua Fishman were recipients of the reached the end of our journey enjoying Paul Wrighton and Samira Musah both Chemical Biology Interface Training good laughs and intellectual conversation got engaged. Congratulations! Samira

52 will defend soon and will be heading to Weiss’s group at UCSF. San Francisco Collaborations between the project Harvard Medical School to work with is a big change from Adam’s small-town teams have been occurring inside and Donald Ingbur. Joseph Klim is already at Canadian roots, but he seems to be outside of the lab. Paul Wrighton and Harvard in the Eggan Group starting his enjoying the beach, working on his tan, Virginia Kincaid performed at the IPiB postdoctoral training. New IPiB student and soaking up the big city life. Senior Art Show last spring with their graduate Yefim Zaltsman and senior grad student graduate students Daniel Zwick and student band, the Pearl Snaps. The Paul Wrighton have been active in sharing Rachael Sheridan continue to be the Biochemistry Addition has never rocked the importance of stem cell research with microscopy and flow cytometry gurus of so hard! Kiessling Group yoga has become the public through Wisconsin Stem Cell the lab, while newcomer Joshua Fishman a favorite activity the past few months, Roundtable outreach programs. Rounding brings a strong background in polymer involving taking classes at lab members’ out the team is Pun Wangkanont, a synthesis to the team. We bid farewell to favorite studios around Madison. Namaste! former undergrad in the group who has Postdoctoral Fellow Jonathan Hudon as In other news, we welcomed Kayte returned to the nest. he moved overseas to further his training Cunningham to the group as a coordinator Team Chemotaxis said goodbye to with Peter Seeberger in Germany. for the Chemical Biology Interface Margaret Wong as she defended her thesis Team Multivalency continues to gain Training program. Becca Splain began her and took a postdoctoral position with insight into the function of DC-SIGN postdoctoral work in the Van Der Donk Novartis in Boston. Graduate student using glycomimetics. Lynne Prost finished laboratory at the University of Illinois- Heather Hodges has picked up the her tenure as a Postdoctoral Fellow Urbana/Champaign. The Kiessling Group reigns, bringing youthful exuberance to in the Kiessling Group and is now an wishes the best of luck to Libby Schmidt the project. Heather recently adopted a instructor for the capstone undergraduate as she finishes her undergraduate degree kitten, Tugsly, who is quickly becoming biochemistry laboratory course here at and ventures out into the world. We’ll miss a lab mascot. The Kiessling Group sends UW-Madison. We’re elated she moved you, Libby! our best wishes to former chemotaxer only one building away and can still visit If you were not mentioned above, it Anthony Fowler. the lab from time to time! Since receiving may be that we haven’t heard from you in The B Cell Bombers added another his PhD this summer, Shane Mangold has awhile. If you are a former group member, dissertator to the team last spring as returned west to work with Bob Grubbs we’d love to learn what you are up to. Nitasha Bennet passed her prelim. B cell at CalTech. Joseph Grim is holding down Please drop us a line and stay in touch. The big brother Adam Courtney wrapped the fort and excited to further elucidate Kiessling Group looks forward to another up his PhD and is now a postdoc in Art the role of DC-SIGN in immunity. highly successful and fun-filled year.

The Kimblecell cycle effects with key similarities to its across the street as a Senior Scientist in the lab has seen human Tob/BTG homologs and has now Genetics Department with Xin Sun. many significant joined a Madison biotech company; and Despite all the departures and events since our Clint Morgan completed his innovative transitions, the lab remains a lively and fun last newsletter analysis of chemical reprogramming the place to be. Some people are continuing contribution in sperm-oocyte decision and then returned and making great progress, while others 2010. Five graduate to med school to complete his clinical have just arrived and are finding their feet. students have training — he officially gets his Dr. title Three dissertators are well on their way completed their in June 2013 when he also completes towards that golden moment of getting Kimble lab Ph. D. degrees and his M.D. We’ve just learned that he has their degree: Elena Sorokin is making moved on. Kyung Won (Kai) Kim finished matched with a residency in surgery here progress toward completing her genomic her lovely analysis of GLD-2/RNP-8 and at UW-Madison and so we won’t have to analysis of sperm-oocyte reprogramming; its regulation of the oocyte program, say good-bye for a few years!! In addition Dan Noble is midstream in his analysis of and is now doing her postdoc with Dr. to those graduate students who left, Aaron how FOG-1 and FOG-3 proteins regulate Yishi Jin at the University of California Kershner completed his Ph. D. degree the sperm fate; and Heiji Shin joined in San Diego; Johan Jeong integrated with ground-breaking work on FBF Aaron Kershner and quickly became a the network controlling germline stem targets of self-renewal, but then broke the central player in our analysis of lst-1 and cell (GSC) stem cells with the cell cycle mold and decided to stay on to analyze sygl-1. In addition, two graduate students machinery and then moved to Stanford lst-1 and sygl-1, two new and mysterious started their journeys towards a Ph.D.: University for a postdoc with Dr. Thomas genes that he discovered towards the end Aman Prasad began the research phase of Rando; Dyan Morgan laid the foundation of his thesis research. These new genes are his M.D./Ph.D. degree in fall 2012, and for understanding GSCs in XO males major regulators of GSC self-renewal and Kim Haupt joined the lab at the end of and then returned to her home state of very exciting!! The one other departure has the year. It will be fun to see how their Kansas to work with Erik Lundquist in been Dr. Jamie Veryheyden, a postdoc thesis projects evolve. a postdoc that combines research and who made important contributions to the Kimble lab postdocs are also making teaching; Josh Snow discovered FOG-3 sperm-oocyte decision, and then moved great strides. Senior postdoc Dr. Kyle

53 Friend completed a terrific piece of work the analysis of environmental effects on start his own independent project. showing that PUF and Ago proteins work physiology, including effects of starvation In addition to these comings and together in both worms and humans on germline stem cells; and Dr. Erika goings punctuated by terrific scientific to regulate translational elongation. Sorensen-Kamakian did her graduate progress, we’ve also seen a lot of action And now Kyle has secured himself a work on Notch signaling in mammalian on the baby front. Is there something in position for next year on the faculty cells at the University of Minnesota and the lab water supply again? In 2011, we of Washington and Lee University in is now tackling similar questions in vivo welcomed Nathan Friend in October, Lexington Virginia!! Congratulations with C. elegans. Anthony William Noble in November and Kyle!! In addition, Dr. Amy Groth, who We’ve also had a number of talented Nathan Geoffrey Kamakian in December; is working on Notch transcriptional undergrads in the lab. Tram Lai, Taylor in February 2012, Ethan Myung Wan controls, has accepted a position on the Bailey and Hannah Gemrich each worked Aoki arrived and in February 2013, Anika faculty of Eastern Connecticut State here for a summer, while Tyler Hansen Mohantey was born. Lab parties are lively University in Willimantic, Connecticut!! and Andrew Krawczyk have projects that if a bit hectic!! Congratulations Amy!! Three other will develop into senior theses. In addition, Sarah Crittenden, Anne Helsley, postdocs have joined the lab since the Marco Ortiz from the Undergraduate Jadwiga Forster and Peggy Kroll-Conner last newsletter: Dr. Scott Aoki did his Program on Genomic Sciences [National are also still making miracles happen, each graduate work at Harvard University, Autonomous University of Mexico in her own way, to keep the lab happy working on protein structure, and is now (UNAM) in Cuernvaca] was in lab for a and thriving. And me (Judith)? I’m still tackling macromolecular complexes that year to do a senior thesis project, which he hanging in there. That’s it for now -- this control C. elegans germ cell fates; Dr. did with Dan Noble. After a few months is obviously the short version of news from Hannah Seidel did her graduate work at home to defend his thesis, visit his the Kimble lab, so please stop by to say at Princeton University working on C. family and get his visa, Marco has now hello and get caught up if you are in the elegans evo/devo and has now turned to rejoined us to complete that project and neighborhood!!

Moving onward in May 2012 to return to China where 2012. and upward: Kaifeng is the Principal Investigator of the Hesamaddin (Hesam) Dashti another Four graduate NMR Group at the State Key Laboratory Biophysics student, also joined in 2012. students completed of Phytochemistry and Plant Resources in their PhD degrees: West China, Kunming Institute of Botany, New postdocs: Kuang-Lung Kunming, Yunnan, China. Dr. Jameson Bothe was recruited Hsueh in Fall Dr. Arash Bahrami was recruited to a from the University of Michigan, where 2011. He is now California start-up company, NetSeer Inc. he completed his Ph.D. with Hashim at the Academia (Contextual Advertisement Targeting), Al-Hashimi. Jameson is working on the Markley lab Sinica in Taipei as where he is a Senior Data Scientist. thermodynamic properties of the IscU a postdoc and is applying for academic Dr. Roger Chylla resigned his position system. positions in Taiwan. Jin Hae Kim and after becoming lured away to become the Dr. Jaime Stark joined from the Jimmy Ellinger in the summer of 2012. Chief Technology Officer at HealthMyne University of Nebraska, Department of Jin married recently and is staying on as a Inc., a Madison-based company developing Chemistry, where he completed his Ph.D. very productive postdoc. Jimmy moved to innovative medical imaging and analytics with Robert Powers. Jamie is collaborating Minnesota in December 2012 to take up systems for health care providers. on metabolomics projects and setting up a a post-doctoral position in the laboratory Dr. Jordan Burke, after completing small molecule protein screening platform. of Claudia Schmidt-Dannert in the Dept. her Ph.D. with Sam Butcher at the end Dr. Vincent Chen came from Duke of Biochemistry, Molecular Biology & of 2012, joined the staff of NMRFAM University, where he trained with Jane and Biophysics at the University of Minnesota. as a short-term postdoc. She trained David Richardson. Vincent has experience Ziqi Dai completed his PhD at the end NMRFAM staff members and users in in developing software to visualize and of 2012, has married, and is now working SAXS data collection and analysis for validate NMR structural constraints and at Epic Systems, a healthcare software about four months before leaving for a is splitting his effort between BMRB and company located in Verona. postdoctoral position at UCSF. NMRFAM. Dr. Kiran Sigarapu and his family M. Francisca Jofre has left her part- have returned to India where Kiran is a time job with BMRB and NMRFAM to Visiting professors at NMRFAM: Ramanujan Fellow at the Center for NMR work full time as an Outreach Specialist in Prof. Valerie Copie from the and Structural Chemistry, Indian Institute the College of Letters and Science. department of Chemistry & Biochemistry of Chemical Technology, Hyderabad, at Montana State University is spending India. They reported the birth of a baby New graduate students: part of her sabbatical at NMRFAM during boy in July 2012. Tala Suidan a graduate student in the the month of April. Dr. Kaifeng Hu and his family left Biophysics Program, joined the lab in Prof. Oleg Dmitriev from the

54 department of Biochemistry at the FEECO International) will be installed is now working well and is fully booked University of Saskatchewan, Canada plans and tested at UW and at Maple Leaf Dairy. by users. See the website (http://www. to spend a sabbatical at NMRFAM from Saleable products to be produced from nmrfam.wisc.edu) for information on July 1, 2013, to June 30, 2014. Oleg has manure include garden mulch, fertilizer new NMRFAM software. been a long-term NMRFAM user starting pellets, cellulosic ethanol, and protein for BioMagResBank (BMRB). The NIH with his days with Bob Fillingame. animal feed or bacterial culture media. The National Library of Medicine (NLM) has Prof. E. Sonay Elgin will be spending project also will produce biodiesel from funded BMRB since it was founded in a sabbatical in the lab from August 1, oilseed grown on at Maple Leaf Dairy. 1990, but NLM support will terminate in 2013, to July 31, 2014. Sonay received her For information, see http://www.are.wisc. September, 2014. We met with potential Ph.D. here in 2002. edu/. funders (NSF, NIH, and DOE), but none Mitochondrial Proteome Project of them provided a positive response. News from former lab members: (MPP). We are now into the third year of The concern of the biological NMR Brian Volkman and Kristin have a this project, supported by the PSI:Biology community over the future of BMRB led daughter (Emi) born in time for their Program of NIH National Institute of to a supportive publication (Nat Struct Mol Christmas card. General Medical Sciences (NIGMS). MPP Biol. 2012 19:854-60). We were informed Ian Lewis and Jen have a second son is paired with the Northeast Structural subsequently that NIGMS would consider (Soren) born in March 2013. Genomics Consortium headed by Guy a “R01” grant application in support of Montelione. Dave Pagliarini (MPP Co-PI) BMRB. John and Eldon submitted a grant Grants and Equipment: and John (PI) are attending a “Mid-Course application in February, 2013. The BMRB Accelerated Renewable Energy Review” by an external panel at Rutgers website (http://bmrb.wisc.edu) has been Consortium. John served as the in early April. The MPP has over 20 revamped and now has greatly improved “corresponding PI” on a grant collaborating biologists and biochemists search capabilities. application to the US Biomass Research who have nominated targets for structure/ and Development Initiative along function studies. The project is paying off Meetings and travel: with UW professors from Ag and with interesting structures and functional Several lab members attended the Applied Economics, Biological Systems results (http://www.mitoproteins.org/). XXVth ICMRBS meeting in Lyon, France Engineering, Soil Science, and Extension NMRFAM. With the demise of last August. and Soil Net, a small local business. In the NIH National Center for Research Several lab members will attend July, 2012, the group received a $7 million Resources, the NMRFAM grant was the Gordon Research Conference on 4-year grant from the USDA and partnered transferred to NIGMS. The Bruker 700 Computational Aspects - Biomolecular with Maple Leaf Dairy in Cleveland, WI, MHz NMR spectrometer on loan from NMR, May, 2013. We look forward to which provided a 20% in-kind match. the Great Lakes Bioenergy Research seeing Ian Lewis, who has been invited to Their project, Accelerated Renewable Center, has been moved to part of John give a talk there. Energy, has the goals of utilizing cow Ralph’s space in the new Bioenergy manure to produce bio-products, reducing Research Building at the intersection of Late breaking news: the environmental impact of manure, and Old University and Campus Drive. A Woonghee Lee successfully defended sustainably maintaining cropland fertility. Bruker Nanostar SAXS system (product his Ph.D. thesis on April 5, 2013, Technology developed by Wisconsin of a shared instrumentation grant that becoming #43 on the Markley lab Ph.D. businesses (Soil Net, Braun Electric, and Sam Butcher wrote) has been installed and list.

This was a great highly competitive result in a blind will soon begin his postdoctoral work with year for the assessment for predicting mutagenesis Teresa Head-Gordon in the Departments Mitchell lab! effects on protein-protein interactions. of Chemistry, Bioengineering, and Following excellent Mitchell lab alumni also landed two Chemical & Biomolecular Engineering results in a CAPRI choice postdoctoral positions. Xiaolei and the University of California at assessment on Zhu accepted a position with Daisuke Berkeley. classifying de novo Kihara in the Departments of Biological designed interfaces Sciences and Computer Sciences at Purdue able to bind, we University. Omar Demerdash completed Mitchell lab achieved another the MD portion of his MD/PhD work and

55 In just two years, is directed toward exploring the role of and brain function. Currently, Lucas is the number of DNA and histone methylation in de novo mentoring two undergraduates Kyung graduate students lipogenesis. Kim and Jia See. Kyung is a senior and she in our lab has grown Laura Bond is a second year graduate is investigating the role of SCD2 in smell. exponentially. We student in IPiB. She hails from Rochester, Jia is also a senior and is studying how welcomed four MN and received her B.A. in chemistry from fatty acids affect the path of pre-adipocyte new graduate St. Olaf College. Laura’s project focuses on differentiation. students and said SCD isoform 3 and fatty acid transport Maggie Strable is a fifth year goodbye to three between tissues. Laura is mentoring two Nutritional Sciences graduate student. Ntambi lab senior members. senior undergraduates, Tamin Rajakumar Her primary research project focuses on With more hands at the bench, we are and Samir Joshi. Tamin is studying another understanding the potential differences expanding our areas of research. In unexplored SCD isoform, SCD4. For her in the metabolic effects of the hepatic addition to continuing to unravel the role senior thesis project, she is characterizing monounsaturated fatty acids oleate and of stearoyl-CoA desaturase-1 (SCD1) in the SCD4 knockout mouse that our lab has palmitoleate. Maggie has two excellent lipid metabolism, we are now investigating recently generated and aims to determine undergraduate biochemistry students the functions of the other mouse isoforms, the effects of deletion of this heart-specific working with her, Nick Friedlander and SCD2-4. SCD isoform on cardiac fatty acid content. Kristin Harrington. They investigate the Since 2011, we have said goodbye to Samir Joshi is a senior biochemistry major metabolic role of SCD1 in extrahepatic Lacmbouh Ade, Matthew Flowers, and and has been optimizing genotyping of tissues such as the skin and brain. Although Xueping Liu. Ade was using tissue culture our newer mouse lines. He graduated in Maggie is busy with her research projects, and mouse models to investigate the effects December and will pursue a career as a she is looking forward to going to Uganda of SCD1 deletion in skin. After two years physician assistant. this year with the annual study abroad in the Ntambi lab, he has moved on to Sabrina Dumas is a first year program lead by Dr. Ntambi and John attend medical school here at UW. Matt Nutritional Sciences graduate student and Ferrick. was a postdoctoral fellow in our lab and all of us are excited to welcome her on Dr. James Ntambi continues to teach now is an Assistant Scientist for Jon Levine board. Sabrina is originally from Trinidad and lead a study abroad program entitled in the Department of Neuroscience. Matt and Tobago and completed her B.S. in “International Health and Nutrition" for recently published a paper that concluded Nutritional Sciences at the University of undergraduates that come from several that combined adipose and liver deletion of Arizona. She is interested in studying the disciplines across campus. Ntambi and his SCD1 does not protect mice from obesity. ketogenic activity of SCD1 deficient mice. colleague John Ferrick teach students in a Liu, who was also a postdoctoral fellow When not in lab, Sabrina can usually be seminar style course focusing on education, in our lab, is now working as a research found eating pizza, watching movies or agriculture, culture and healthcare system scientist at Regulus Therapeutics located running. in Uganda. This is followed by a three week in San Diego. Regulus Therapeutics is Lucas O’Neill is a second year graduate trip to Uganda, during the winter break a biotech company that uses miRNA student in IPiB. He is originally from where the students work in the villages and technology to design new treatments for Pittsburgh, PA and received his B.S. in see nutritional, environmental, and public diseases such as cancer and diabetes. Before Biology at The University of Pittsburgh health problems first-hand. They visit rural Liu left, he finished a project investigating at Greensburg. Lucas is fond of the great health centers, HIV/AIDS clinics, and the role of SCD1 deficiency in one-carbon restaurant scene in Madison and he loves child nutrition centers. While in Uganda, metabolism. to spend his time off traveling to places like the students utilize what they have learned Ahmed Aljohani is a new graduate Noah’s Ark and Mall of America. In the lab, in the course to complete a project on student in the Endocrinology and Lucas is focused on determining the role of resolving an issue of their interest. In Reproductive Physiology Program SCD2 in a tissue specific manner. Moreover, addition, the students periodically receive (ERP). He is interested in discovering the he is interested in how monounsaturated hands-on experiences by participating in mechanism by which SCD1 deficiency fatty acids produced by SCD2 affect the construction of water tanks to provide protects against high carbohydrate or various physiological functions such as clean water to the rural communities they high fat diet-induced obesity. This work glucose clearance, bone development, visit. Students describe their experience

56 as unique and transforming. Please take and education in rural Uganda; and in scientific research, he has been awarded a moment to visit the Uganda program’s to facilitate collaboration between the the American Society for Biochemistry and webpage: http://www.biochem.wisc.edu/ University of Wisconsin-Madison students Molecular Biology (ASBMB) Award for uganda/. and Ugandan grassroots organizations in Exemplary Contributions to Education. Dr. Ntambi also serves as an advisor working for this cause. You are always welcome to stop by and for the Village Health Project (VHP). Dr. Ntambi’s involvement with Uganda talk with the members of our lab - our Established in 2005 by his Uganda study does not stop there. He is also helping to doors are always open. More information abroad students, the organization seeks advance basic research in global health about our research and publications can to aid people by supporting sustainable education and training in Africa. As a be found on our website: http://www. projects that improve sanitation, nutrition, result of Dr. Ntambi’s accomplishments biochem.wisc.edu/faculty/ntambi/

Hello from the from the livers of mice following both including IPiB students Jon Stefely and Pagliarini Lab on acute and chronic perturbations. IPiB Andrew Reidenbach, work closely with the the 4th floor of graduate students Amelia Still and protein biochemists and crystallographers the Biochemistry Brendan Floyd are preparing a manuscript of the MPP to elucidate the structure and Addition! This is that similarly evaluates mitochondrial function of these key proteins. Jon and our first official reversible acetylation – a PTM whose Andrew, along with crystallographer Craig “Letter From prevalence and importance now rivals that Bingman, senior technician Adam Jochem the Lab,” having of phosphorylation. These studies are part and undergraduates Jaclyn Saunders and first introducedof some exciting and productive ongoing Grant Barber (now at Harvard Medical Pagliarini lab ourselves in a New collaborations with the Coon, Attie and School), among others, are preparing a Faculty Profile in the last Newsletter. Since Denu groups on campus. manuscript that describes the structure and that time, we have continued to grow 2. Mitochondrial adaptation to function of a novel mitochondrial kinase into a diverse and vibrant group of 10 nutrient stress. Changes in nutrient that is mutated in a cerebellar ataxia. graduate students, 2 postdoctoral fellows, availability often require more drastic Fortunately, our early work has helped a senior technician and a great team of 6 alterations to the mitochondrial us to receive multiple honors and awards undergraduates. Together, we continue to infrastructure, involving transcription during the past few years that help to fund study mitochondria – the tiny metabolic and post-transcriptional processes. In a our program. Dave received Searle Scholar, machines that comprise 10% of our bodies manuscript recently published in Cell Glenn Foundation and Shaw Scientist – and the biochemical underpinnings of Reports – led by CMB graduate student awards. Paul Grimsrud received an NIH mitochondrial dysfunction in both rare Jarred Rensvold – we described the F32 postdoctoral fellowship. Amelia Still and common human diseases. It has been widespread mitochondrial remodeling that received an NSF graduate fellowship. Jon a real privilege to build a research program occurs when cells are deprived of iron. Stefely received an NIH F30 Physician like this in Madison, where there is a long Our work suggests that mitochondrial Scientist award. Josh Carson received an and rich history of world-class metabolic dysfunction may be a central problem in American Heart Association predoctoral and mitochondrial research. In particular, iron deficiency, which is the #1 nutritional fellowship. Undergraduates Grant Barber our group has developed three focus areas: disorder worldwide. and Athavi Jeevananthan received Hilldale 1. Rapid mitochondrial modulation 3. Functional investigations of awards. Grant and Athavi were also was by posttranslational modifications mitochondrial proteins mutated in also selected to participate in the SCORE (PTMs). It’s long been known that cells human diseases. As a postdoc, I led an and Khorana programs, respectively. use PTMs for tweaking protein function integrative genomics and proteomics Amelia Still, Jarred Rensvold, Molly and for an array of signaling processes. study to define the protein composition McDevitt and Kelly Werner are funded However, the nature and importance of mammalian mitochondria. Four years by the Molecular Biology Training Grant of PTMs for regulating mitochondrial later, hundreds of proteins in this so-called (MBTG), Brendan Floyd is funded by function has remained unclear. We believe MitoCarta list have no known function, the Molecular and Nutritional Sciences that PTMs are widely important for including many that are associated with Training Program (MANTP), and properly altering mitochondrial activity to human diseases. A long-term goal of my Danielle Lohman is funded by the maintain homeostasis, and that elucidating group is to elucidate the biochemical Biotechnology Training Program (BTP). the signaling processes at play could activities of these proteins as a first step Last, we are also grateful for our funding lead to novel therapeutics for metabolic toward devising therapeutic approaches for from the NIH (NIDDK and NIGMS) and disorders. To that end, we recently their associated diseases. Toward that goal, the USDA. published a paper in Cell Metabolism I co-direct (along with John Markley) the We hope to report exciting new stories – led by postdoc Paul Grimsrud and Mitochondrial Protein Partnership (MPP), from each of our research themes in the CMB graduate student Josh Carson a structural genomics consortium that is next Newsletter. In the meantime, check – that describes the dynamic nature of part of the NIH’s larger Protein Structure out our lab website (www.pagliarinilab. mitochondrial reversible phosphorylation Initiative (PSI). Members of my group, org) for the latest news and publications! 57 Hello Biochemies now working out at the UW hospital with really owed to Paul for the Herculean job and other Team Jim Gern, and collaborating on many he did in Ann’s absence, to bring together Palmenberg facets of the rhinovirus C directions. A what is widely acknowledged as the best alumni! Thismajor cooperative team project between ASV ever (our 5th in Madison). During past year was Jim, Ann and John Yin (UW Engineering), the meeting (1600 virologists) Jean-Yves quite interesting linking rhinovirus biochemistry with Sgro and Adam Steinberg taught a mini- to say the least, asthma exacerbations, was just funded, course on bioinformatics. Students from and it’s time to so picornaviruses will live on for quite all the campus virology labs organized and bring you up to some time in the lab. It’s a very productive ran the first ever “Virolympics,” a series Palmenberg lab date. Marchel, as time experimentally, primarily catalyzed of virus-related brain-teaser and physical always has been shepherding students, by great students, Marchel and local games that were part of the meeting grant funding and purchasing to keep collaborative faculty support. entertainment package, and the Hepatic the lab humming. Kelly Watters, Holly As perhaps you’ve heard, Ann was Lesion Band (herpes virologists) also Basta, Ryan Petty, Valjean Bacot- diagnosed with an aggressive form of played, to the delight of everyone. Who Davis and Jessica Ciomperlik are all lymphoma in the fall of 2011, and spent knew virologists were so talented? Ann now dissertators and well on their way about 7 months out of the lab in treatment has now permanently retired from ASV to respective degrees. Kelly had an and rehab. But she’s now baaack… mostly planning (the 2017 Madison meeting will excellent paper published in JVI last full time, mostly mobile, and picking up be run by Kristen Bernard), and Paul is year on the rhinovirus 2A proteases, and the pieces. Remission is a good thing! now the official director of the IMV. Lots Ryan just had a neat EMCV Leader:Ran During the dark days, Paul Friesen stepped of changes, but all for the good! Ann, biochemistry story accepted there as well. in like a champ, both to run the day-to-day now free from many campus and national About 5 more papers involving various functions of the Virology Institute, and to committees (dropped when she was sick), combinations of the whole cast are in complete preparations for the American is continually getting stronger and now the works (as usual, Ann is the slow part) Society for Virology annual meeting, held “free” to focus on the fun part of science. and these include a wonderful modeling July 21-25, 2012 at the Monona Terrace. Many thanks to all of you who wrote, story for the rhinovirus C capsid (Holly), Ann was semi-functional by then, but she called or beeped to give your support over Leader:kinase interactions (Jess), and mostly schmoozed with friends and rode the last year. Friends and colleagues are NMR structures and biochemistry of around on a little red scooter to save (her) what make this all worthwhile. Leader:Ran (Valjean). Yury Bochkov is energy. In truth, phenomenal kudos are

Big changes big news is that Professor Phillips has Scientist Craig Bingman holding down in the Phillips 'retired' from UW, and is now Professor Phillips Lab North. Phillips Lab South laboratory. Several Emeritus. This does not mean he's quit is now fully functional and we regularly folks successfully working however, as Rice University have joint Skype lab meetings with both completed their hired him back as the Looney Professor sites involved. Drs. Hongnan Cao and Ph.D.'s since of Biochemistry. The lab at UW will Ragothaman Yennamalli moved to the last update, keep on keepin' on for a while as Kate Rice with Dr. Phillips and have been including Chris Helmich is still working on her Ph.D at continuing to work on projects started at Bianchetti, Aram UW. UW grad student Jerry Wang has UW-Madison. Phillips lab Chang, Aaron moved to Rice to complete his studies, Bryden, and Crane Zhang. But the but that still leaves Kate, Bob Smith, and

58 The Pike laboratory that determine the differentiation of expression of the gene for Rankl (Tnfsf11). has been active precursors into either osteoblasts or There, she focused specifically upon the over the past year adipocytes. Mark received an award from consequence to the skeleton of deleting using genome-wide the 15th Vitamin D Workshop to travel one of at least 7 of the enhancers that methodologies to to Houston, Texas in June of 2012 and a control the expression of this gene. To explore both the 2012 Young Investigator Award from the extend this work, we prepared three mouse process of cellular American Society of Bone and Mineral strains each of which contained a unique differentiation Research (ASBMR) in Minneapolis, MN Rankl enhancer deletion. Dr. Onal is and the actions in October of 2012 for his work in these now exploring the consequences of these Pike lab of vitamin D research areas. These studies are supported deletions on the immune system, the in cell types that play a central role in by the NIH. skeleton and in other tissues where Rankl bone metabolism. To this end, we have Dr. Seong Min Lee was recently plays a role. Her work now confirms that discovered that the extensive transition promoted to Assistant Scientist for his work our molecular approach using ChIP-seq from mesenchymal stem cells to mature that has focused upon the mechanisms analysis to define the nature and scope osteoblasts and then osteocytes involves that underlie the regulation of the vitamin of a regulatory gene locus is a useful one widespread, yet specific, qualitative D receptor (VDR) gene in bone and other to identify key regulatory regions both in and quantitative changes in numerous cell types. These studies have identified vitro and in vivo. She has been aided in this epigenetic histone marks that define regulatory regions within the VDR gene project by Ms. Allison Danielson, who is specific chromatin states at genes known that play a central role in auto-regulation an undergraduate student in Biochemistry to highlight each specific cell type. These by the vitamin D hormone in bone cells at the University. A renewal for this work marks, together with de novo binding and/ and in the gene’s regulation by PTH as well. was recently funded by the NIH. or displacement of bone cell transcription In unique studies, Seong Min has deleted Hillary St. John is a third year factors such as RUNX2 and SP7, and their individually these regulatory enhancers graduate student in the IPiB Biochemistry regulatory complexes appear to orchestrate within the context of a large segment of Program at the University of Wisconsin, the changes in gene expression that are DNA that contains the entire expression and holds the Hector F. Deluca Fellowship observed during the differentiation process. and regulatory locus and introduced them Award for the second year in a row. Hillary Interestingly, exposure to the vitamin stably into cell lines and as transgenes in is interested in bone cell differentiation D hormone at specific times during mice. These studies are among the few that and together with Dr. Katie Bishop this transition results in unique cellular explore the role of regulatory regions both initiated a project aimed at understanding responses at both the DNA as well as RNA in vitro and in vivo. They appear to confirm the molecular basis for the osteoblast to output levels. Further studies at the level our view that these regions are critical for osteocyte transition. Osteocytes, derived of specific vitamin D target genes in vitro VDR gene regulation. Additional studies from the osteoblast lineage, represent and in vivo have identified mechanisms ongoing include an examination of the the most predominant cells of bone, and whereby the hormone regulates biological effects of mutant VDRs introduced into in recent years have become the focus of processes that include bone resorption, the global VDR-null mouse. These and intense research as they play both a central bone mineralization, stress responses, other studies are supported by the NIH role in bone remodeling and an endocrine and growth control, among others. These and were presented in scientific sessions role in the production of the phosphate ongoing studies have been exceedingly at the ASBMR meeting in Minneapolis in homeostatic hormone FGF23. Having fruitful; many of these discoveries have 2012. identified a unique cell line capable of been selected for presentation at national Dr. Chang-Hun Lee is now the osteoblast to osteocyte transition, meetings held during the past year. completing his 4th year in the laboratory. Hillary is exploring the changes that Dr. Mark B. Meyer has now been Chang has focused during the past year occur to the transcriptome as well as the promoted to Associate Scientist in the on a study of the transcription factor underlying changes that occur to the laboratory, and directs both our DNA SP7, a transcription factor induced by the epigenome on a genome-wide scale. She sequencing and bioinformatics efforts to RUNX2 bone cell master regulator and is aided in this endeavor by Ms. Sydney explore the mechanisms that are involved which is essential for the formation and Hansen, an undergraduate student in in differentiation and gene regulation. He differentiation of osteoblasts. A genome- Biochemistry who has proven skillful in has been aided in this endeavor by Ms. wide analysis of binding sites for this the numerous molecular cloning efforts Nancy A. Benkusky, who was recently transcription factor has provided a larger that are also part of this project. Numerous employed as an Assistant Researcher in the view of the genes that are regulated by surprising observations have been made lab. She has rapidly learned the methods this factor and is providing clues as to its that highlight the osteocyte transition that are a prelude to conducting deep central role in osteoblastogenesis. and the genes that are either suppressed sequencing analysis, and many additional Dr. Melda Onal has recently joined or upregulated. The role of vitamin D in analyses that are central to our research our group as a Research Associate, having osteocyte biology is also being explored. effort as well. Mark also has a number obtained her PhD in Professor Charles We anticipate an extensive understanding of biological projects that are ongoing, O’Brien’s laboratory in Little Rock of the molecular changes that occur to including an analysis of the mechanisms where she worked on the regulation of this cell during its differentiation into this 59 unique functioning cell type. This work this process. Using a series of transgenic Erin is central to our successful foray into has been presented in numerous venues mice compromised for VDR, Rankl and genetically modified mouse studies. at the University of Wisconsin and at the ApoE expression or double nulls, Sohel is Drs. Rob D. Nerenz and Kathleen A. ASBMR meeting in Minneapolis in 2012. exploring the contribution of these factors Bishop have left the laboratory over the Alex Carlson is a third year graduate in arterial calcification. past year or more, Rob to an additional student in the Molecular and Cellular Amber Mael is a recently hired Senior Clinical Chemistry Postdoctoral position Pharmacology Program at the University. Research Assistant who comes from the at Wash U St Louis and Katie more His work is focused on the endocrine Morgridge Institute. Amber has extensive recently to a Postdoctoral position with function of the osteocyte, having observed skills in cell culture, particularly as it relates Professor Clifford Rosen in Maine. Their that the phosphate hormone FGF23 is to the preparation of induced pluripotent founding efforts in the laboratory were expressed in the cell line used by Hillary stem cells (iPS cells). To this end, she has considerable and they are missed. Dr. and that it is regulated by the vitamin prepared a series of human fibroblast- and Paul D. Goetsch obtained his PhD in D hormone, PTH, and surprisingly, by smooth muscle cell-derived iPS cell lines December of 2012 and has moved on to the heterodimer PPARg/RXR. Extensive for our studies aimed at understanding the the University of California at Santa Cruz histone modification and transcription early role of RUNX2 in the mesenchymal/ where he is working in the laboratory factor binding analysis using ChIP-seq has preosteoblast phenotype. Amber is also of Professor Susan Strome studying the identified a series of regulatory enhancers involved in numerous additional projects, embryogenesis of C. elegans. Paul’s work that play a role in FGF23 expression. Alex including those involve the preparation of in this laboratory focused upon the is exploring these regulatory regions for bone marrow-derived mesenchymal cell contribution of homeobox gene products their contribution to FGF23 expression. lines from our many genetically altered such as Pbx1 and Meis2 to the regulation As FGF23 plays a central role in vitamin D mouse lines. She is aided in these projects of specific gene targets by vitamin D. metabolism and in chronic kidney disease, by Ms. Tori Osinski, an undergraduate We continue to make new and clarification of the regulation of this in the Biochemistry Program at the unexpected discoveries. As with all hormone is central to our understanding University. scientific endeavors, while many of our of both mineral homeostasis as well as Erin Riley is an Associate Research working hypotheses have been confirmed, disease. Assistant who is responsible for our rapidly an equal number of them have not. This, Sohel Shamsuzzaman, MS, is a increasing mouse colony. It is safe to say together with the emerging literature, third year graduate student in the IPIB we have over two dozen different strains continues to lead us down research paths Biochemistry Program who currently holds of mouse, most arising from our efforts that are totally unanticipated. Thus, the the Kamaluddin Ahmad Distinguished to characterize the regulatory regions of excitement continues unabated. As a Graduate Scholarship. Sohel is interested genes in vivo, but also from our efforts laboratory leader, I consider it a privilege in the mechanisms that underlie smooth to explore the role of the VDR and other to participate in this renaissance in muscle cell reprogramming to the gene products in unique cell types in vivo. transcription research, facilitated largely osteochrondroprogenitor phenotype Erin has played an essential role in our by the phenomenal technical advances that plays a role in the calcification exploration of the VDR gene with Dr. highlighted by massively parallel DNA of atherosclerotic plaques and the Seong Min Lee, the Rankl gene with Dr. sequencing together with the development mechanisms through which the vitamin Melda Onal, and more recently in our of highly sophisticated bioinformatics D hormone, perhaps via Rankl, influences exploration of the Cyp24a1 and Cyp27b1 analyses. This type of research is certainly this process. Accordingly, he has studied genes and others as well. Erin seems able one of the big post genomic payoffs that the ability of osteogenic cocktails to to keep everything under control while at has emerged following the sequencing induce this reprogramming process to cells the same time producing the genetically of the human genome and as happens with an osteoblast-like phenotype and the modified mice that are needed for our frequently in science was completely changes in gene expression that accompany extensive biological studies. It is clear that unpredicted.

60 Departures Arrivals and the rest of the Warthogs ice hockey Since the Though we miss the seven graduate team won the recreation C-league publication of the students who left us, we are excited that championship. last departmental seven new graduate students have joined • Trish Hoang and her husband bought newsletter, seven us. Kalie Mix and Ian Windsor are in their first house. graduate students the IPiB program; Matt Aronoff, Aubrey • Jim Vasta won first place in his age earned their Ellison, Robert Newberry, Thom Smith, group in the Zoo Run Run 5K race. Ph.D. degrees in and Kaylee Underkofler are graduate • In August 2012, at the annual Protein our laboratory. students in the chemistry department. Society meeting in San Diego, alumni Raines lab Amit Choudhary Three postdoctorates have also joined Steve Fuchs, Chiwook Park, Ken became the 25th Junior Fellow in us. Raso Biswas came from the University Woycechowsky, Jason Horng, and Nick chemistry at Harvard University. of Berne, where he worked with Professor Panasik had an impromptu reunion. Greg Ellis remains on campus as a Jean-Louis Reymond. Kevin Desai was • As the holiday party ornament-design postdoctorate with Professor Tim Bugni at Florida State University with Professor winners in 2010 and 2011, the group at UW–Madison, following his marriage Brian Miller, who himself was once rested their creative energies in 2012 and to fellow IPiB student Nicole Beauchene. a postdoctorate with us. And, Brett plan for a spirited reentry in 2013. Sayani Chattopadhyay is working at VanVeller joined us after obtaining his We always keep our webpage up-to- Champion Technologies, a specialty doctorate at MIT with Professor Tim date. Please keep up with us by adding chemical company in Houston. Ben Caes Swager. a bookmark to www.biochem.wisc.edu/ is applying his knowledge of cellulose at Several undergraduates are working labs/raines. There, you can read about our ink manufacturer Siegwerk USA in Des with us as well: Amy Davis, Spencer Peh, latest research and learn the whereabouts Moines. Finally, we bade farewell to three Steve Leeb, Chin Leng Cheng, Kevin of all 44 doctoral and 23 post-doctoral M.D./Ph.D. students: Mike Levine, Walters, Kelly Wallin, Tia Chitwood, alumni. Nadia Sundlass, and Mike Palte. They and Alex Peterson. Although there is continual turnover are completing their M.D. training at As you can imagine, our team of thirty in the lab, we still maintain a collegial various Wisconsin medical centers and (16 graduate students, 6 postdoctorates, atmosphere that fosters creativity and making plans for residencies in surgery, and 8 undergraduates) engenders a highly independence. Please stop by if you are in dermatology, and pathology, respectively. stimulating and productive environment! town – we always enjoy seeing you! Mike also married IPiB student Rachel Kubiak. Current Events Two postdoctorates also left us – • Kristen Andersen, Trish Hoang, Sean Katrina Jensen is an Assistant Professor at Johnston, John Lukesh, Rob Presler, Black Hills State University, and Langdon and Jim Vasta have become dissertators Martin is an Assistant Professor at Warren and continue to progress towards their Wilson College. And, the group celebrated doctoral degrees. the marriage of Caglar Tanrikulu. • Mike Palte, Ian Windsor (in goal),

Renowned red heads Mike Bruesewitz (WI men's basketball player, 6'6") and Sean Johnston (IPiB student/Raines group, 6'5").

61 The last year or so be more readily degradable (to improve basic and practical implications – the has been pretty biomass conversion energetics), the compound is quite useful!); establishing exciting in the group has been involved in: discovering a new ‘zip-ligninTM’ approach (cover Ralph Lab, where the first monolignol acyltransferase and article in ChemSusChem); delineating the students, postdocs, successfully downregulating it in grasses; role of a ‘domain of unknown function’ and researchers discovering new types of lignin monomers gene involved in xylan biosynthesis (cover are involved in and an entirely new natural homopolymer article in the Plant Journal); developing a range of often from the ‘missing monolignol’, caffeyl fluorescence-tagged monolignols that are collaborative alcohol (PNAS cover article and Science receiving considerable interest; and on Ralph lab studies on plant highlight); discovering a new lignin and on – it has been a very productive and cell wall biochemistry. On the way to monomer from an alternate biosynthetic exciting time! attempting to engineer plant lignins to pathway, the flavone tricin (which has

Three journal covers from our cover articles. Two of them are from Yuki Tobimatsu’s articles – we are thinking he should write all the Lab’s papers from now on (or at least submit them)!

We’re thriving in Ted Gries (former lab member and ’10 in water, of relevance for understanding our new space in IPiB PhD, now a Chemistry professor at how biochemical solutes like urea and the Biochemical Beloit College) recently became the proud osmolytes interact with proteins and Sciences Building, parents of daughter Winifred. IPiB student nucleic acid as well as for understanding and are delighted Sara Heitkamp, who also obtained her the contributions of various noncovalent to have visitors! PhD last summer, characterized the series interations to protein and nucleic acid One focus of of large conformational changes needed self-assembly processes. IPiB student Ben our research is on to insert the promoter DNA in the cleft. Knowles is studying polyols and ethylene determining the Sara is now a Scientific Development glycols, in order to understand both the Record lab mechanism by Program Fellow with Beckman Coulter. chemical interactions of these solutes which the RNA polymerase molecular Chemistry graduate student Emily with proteins and nucleic acids and the machine puts promoter DNA in the Ruff and Biophysics graduate students physical effects (excluded volume effects) active site cleft, opens it using binding Raashi Sreenivasan and Jan Murray are of polyethylene glycols, which of course free energy, and then stabilizes the studying the roles of other polymerase are widely used to crystallize proteins initial unstable open complex by folding elements, promoter sequence variants and or assembly multi-subunit complexes. and assembly of mobile regions of transcription factors in these key steps of Chemistry graduate student Emily core polymerase on the downstream transcription initiation. Undergraduate Guinn is quantifying interactions of urea, duplex. We’re now able to ask more Biochemistry majors Dana Bellissimo osmolytes, Hofmeister salts and other detailed questions about what regions of (now in the MD-PhD program at Penn), solutes with functional groups of proteins polymerase carry out these steps, and how Mark Kraemer (now at UW Medical and nucleic acids, to determine why urea they are regulated. IPiB student Amanda School) and Kristin Zorn (now in Sarah is a protein and nucleic acid denaturant Drennan, who obtained her PhD last Ades’ laboratory at Penn State), mentored while most osmolytes are protein stabilizers summer, characterized the dramatic by Amanda, Sara, and Emily, were quick (though not of nucleic acids), and why the consequences of deleting a mobile region learners and contributed a lot to these stability of protein-nucleic acid complexes of core polymerase or an in-cleft region projects while doing their senior theses on is increased so greatly, particularly at of the specificity (sigma) subunit for this challenging system. high salt concentration, by replacing the the kinetics of both early and late steps The second focus of our research is on laboratory salt KCl by the physiological of this process, and on the properties of quantifying noncovalent interactions of salt KGlutamate. Ben and Emily will the final open complex. Amanda and individual biochemical functional groups obtain their PhD degrees this semester. 62 Both have been assisted in their research Senior lab members are Mike Capp in Chemistry at UNESP (Sao Paulo State by many very capable Biochemistry or (who is pioneering the development University). Scientists Ruth Saecker Chemistry undergraduates and senior of solutes as probes of coupled folding and Laurel Pegram have also left the thesis students, including Michael Kerins in protein and nucleic acid processes, laboratory; all are greatly missed. Laurel (now at Kimberly-Clark), Tyler Wied including transcription initiation) and husband Demian Riccardi (now at (now at Johns Hopkins), Zeeshan Haq and Irina Shkel (whose speciality is Oak Ridge National Labs, previously a (now at UW Medical School), as well as computational analysis of chemical and UW PhD with Qiang Cui in Chemistry) Roger Diehl, Chau Phan, Hyo (Mike) physical (coulombic, excluded volume) recently also became proud parents of a Cha, Rachel Wong, August Melcher and effects of solutes on biopolymer processes). daughter (Ada). Audrey Hartzler, all of whom are now Postdoctoral research fellow Rogerio That’s an update on us; let us know applying to graduate or medical school. Sassonia returned to Brazil and a position about you.

Highpoints and Biochemistry and is currently a Postdoctoral famous chess player, Bobby Fisher (when a summary of the Fellow with Brian Pfleger at UW-Madison he was young and before he went crazy). Weibel lab from studying bioenergy production. Matt Katie Brenner (Postdoctoral Fellow; the past year: is engaged to a former member of the Ph.D., Caltech) recently joined the lab Weibel lab (Abbey Vangeloff). Marie and is working on a diagnostic device for Former High Foss received a Ph.D. in Biochemistry detecting necrotizing enterocolitis. She is School Students: and is currently a Postdoctoral Fellow the recipient of a Postdoctoral Fellowship Congratulations with Georgiana Purdy at Oregon Health from the Hartwell Family Foundation. to former research Science University where her research When not on campus, she can be found Weibel lab assistants John focuses on Mycobacterium tuberculosis. building forts and playing games with her Ntambi and Norah Ntambi who graduated Jack Ho received a M.S. in Biomedical kids. from West High School and currently Engineering and is currently employed John Crooks (2nd year Graduate attend the University of Wisconsin (John: at Epic (Middleton, WI). Daniel Pauw Student, IPiB) develops tools to track the Whitewater; Norah: Madison). received a M.S. in Cellular and Molecular distribution of lipids within bacterial cells Biology 2 and is exploring graduate school to understand how lipid domains affect Former Undergraduate Students: in Information Sciences. Hannah Tuson bacterial physiology and behavior. John has Sonia Carey (née Treviño-Dopatka) received a Ph.D. in Biochemistry and is a passion for playing musical instruments. received a B.S. in Biochemistry from currently a Postdoctoral Fellow with Julie Jenna Eun (6th year, Graduate Student, UW-Madison in May 2012, got married, Biteen at the University of Michigan. IPiB) defends her Ph.D. dissertation in co-authored a paper in Journal of December 2012 and will be a Postdoctoral Bacteriology, and moved to Boulder, CO Former Postdoctoral Fellows: Fellow with Ethan Garner at Harvard. where she is currently teaching. Nate Cira Lars Renner is currently a Group Jenna uses small molecules to study received a B.S. in five majors (including Leader in Molecular Nanosensors at the bacterial cell biology. During summer Biochemistry) from UW-Madison in May Technical University Dresden. Lars received 2012, Jenna improved science curriculums 2012, and is currently a graduate student the Boyer Postdoctoral Excellence Award for elementary and middle school students in Bioengineering at Stanford. In his last from the Department of Biochemistry, in Mexico. She is grateful to biochemists semester as an undergrad, Nate published UW-Madison. that donated time & resources to make the a first author paper in Lab on a Chip, trip successful. co-authored a paper in PLoS One, and I repeated the experiment from 2011, Katie Hurley (3rd year, Graduate was a co-inventor on a patent. Kelsey and asked current members of the lab to Student, Pharmaceutical Sciences) joined Thornton received a B.S. in Biochemistry write a short summary, which you can find the lab in May and passed her preliminary from UW-Madison in 2012, co-authored below. In the few cases where people were exam in July. She is developing inhibitors of two papers (ACS Medicinal Chemistry too busy with research to write something, chromosome segregation and maintenance Letters; the second is submitted), and I improvised. in bacteria to study these mechanisms. started graduate school in Biochemistry at Tristan Abbott (Freshman, Katie is a ballroom dancer and creates The Ohio State University. Zhou Zhong Biochemistry) characterizes the interaction beaded jewelry. received a B.S. in Biochemistry from of RecA with the anionic phospholipid, Piercen Oliver (Postdoctoral Fellow; UW-Madison in May 2012, is currently cardiolipin in collaboration with Manohary. Ph.D., Lehigh) images lipid domains in a research assistant in our lab and with Tristan competes in triathlons and recently bacteria and studies their influence on Walter Goodman (Entomology), and is finished the Racine half-ironman. local biochemistry. He recently received a preparing for graduate school in 2013. George Auer (4th year Graduate Postdoctoral Fellowship from the National Student; Biomedical Engineering) studies Science Foundation. Piercen tinkers with Former Graduate Students: the assembly of the bacterial cell wall. electronics, enjoys cycling, and recently Matt Copeland received a Ph.D. in George has a remarkable likeness to the became a father (Luther Oliver).

63 Manohary Rajendram (4th year mechanisms of protein localization in badminton and table tennis, hiking, good Graduate Student, IPiB) studies protein- bacteria. He had an amazing time teaching food, beer, and music. lipid interactions in bacteria and is having a an undergraduate microbiology lab course Doug Weibel (PI) feels privileged to terrific and productive time in the lab. She in 2012 and is passionate about science, participate in research and education with recently achieved her goal of participating baking bread (including the Brazilian pão tremendously talented undergraduate and in a Taekwondo competition and finished de queijo; Ed: Weibel Lab members have graduate students and postdoctoral fellows. first in an individual form event. never tasted it before), and is contemplating Outside of work, Doug spends time with Madhusudan Rajendran (Sophomore, organizing a lab trip to Brazil in the coming his family: Gina (spouse), Xander (12 yr.), Biochemistry and Math) recently joined year(s). World Cup 2014? Guy (9 yr.), Zoe (7 yr.), and Clementine the lab through the Biochemistry Scholars Earl Yoon (2nd year Graduate Student, (3 yr.). Program. He is conducting research in MDTP) studies the relationship between collaboration with Thiago to study polar phospholipid composition and cell Other Notable News: localization of proteins in E. coli. He enjoys morphology. He is not a hockey fan. Jean-Marie Swiecicki (Ecole Normale playing soccer with his friends. Peter Vander Velden (Junior, Supérieure) returned to the lab to finish Pedro J. Resto (Postdoctoral fellow, Biochemistry) has worked on several up his bacterial motility project and Ph.D. UW-Madison) recently joined the projects, including biofuels production in manuscript during his graduate school lab from Biomedical Engineering. He is bacteria and behavior that protects bacteria vacation (yes, vacation in the lab!). Sergio developing a point-of-care DNA detection from predation. His interests include the Lopez Aristabal (University of San Paulo, system to identify bacteria. Pedro has been a environment, science, energy, Science Brazil) spent approximately six months in Hoofers instructor in sailing, windsurfing, Olympiad, reading, and building chocolate our lab working on several bacteria motility and snow kiting for the past four years and fountains (Ed: the Weibel lab has never projects, returned to Brazil to graduate, divides his attention between two children: tasted one of his chocolate fountains). then returned recently for two weeks to a daughter (4 years) and a newborn son. Zhou Zhong (Research Assistant) is finish up one of his projects.Melissa Ryan Sacotte (Senior, Biochemistry) developing microfluidic devices to study Hemling was a summer intern in 2011 collaborated with Matt and Hannah on the bacterial chemoaxis and is collaborating and 2012 as part of the NSF-sponsored motility behavior of Proteus cells through with Jenna to study small molecular Research Experience for Teachers Program the Biochemistry Scholars Program. He regulators of bacterial biochemistry. at UW-Madison. Melissa is a chemistry spent last summer working at Harley Zhou is from Southwest China and loves and biology teacher at Beaver Dam High Davidson. snowboarding. School in Wisconsin who developed an Hannah Sandock (Junior, Maoquan Zhou (Postdoctoral Fellow; approach to use microfluidics to teach Biochemistry) collaborates with Earl on Ph.D., West Virginia) joined the lab chemistry concepts to her classroom. the structure and composition of bacterial in May, 2012. A synthetic chemist by We hope you will visit us at http:// membranes. She misses her former mentor, training, he has been working on several www.WeibelLab.org to find out recent Lars. projects, including the development of news about our group. If you are in the Thiago Santos (2nd year Graduate potent antibiotics and chemical biology area, please consider stopping by so we can Student, MDTP) studies molecular probes. He enjoys his family, playing give you a tour through the lab.

Greetings from focusing on RNA-protein interactions, to figure out how a protein recruited by the Wickens lab! and developing ways to create designer many regulatory proteins turns down Since the last proteins for new purposes. Melanie translation of specific mRNAs. newsletter, we have Preston, a post-doc from University Four undergrads now assist us: Markus been focusing on of Rochester, has joined the group to Neville, Sam Disalle, John Nielsen and how RNAs are work on uridylation and its role in RNA Mike Harte. Markus has been working controlled, and regulation. on control by PUF proteins, with tutelage how networks of Among the PhD students, Chris from Daniel, and at the same time and is mRNA control Lapointe works on enzymes that control training Sam to take care of our frog colony. Wickens lab are assembled and RNAs by adding untemplated nucleotides; John and Mike are keeping lab running integrated. Lets start by talking about Douglas Porter and Daniel Wilinski are smooth by providing basic support. John the people who are now in the lab; then trying to define networks of RNA control is also starting to do research with Chris’ those who’ve left; then a quick tour of our by proteins, and understand how they help and advice. science; and a final few comments about work, control key events, and evolve. Natascha Buter continues as our Marv. And a plea to stay in touch! Cary Valley has concentrated on RNA- lab technician – ordering, maintaining, protein interactions, trying to enhance advising, training, and at the same time, Current lab members.... their affinity and specificity. Shruti doing experiments with a new entry into Zak Campbell, from U Arizona, has Waghray has been studying proteins the lab menagerie – Neurospora, a fungus joined us as a post-doc, and has been involved in mRNA regulation, trying with filamentous predilections. Natascha

64 keeps the lab running smoothly and addition of untemplated nucleotides. ceremony in the fall. But as it happened, greases our collective skids. We now want to know how they find Marv then was on sabbatical for the Carol Pfeffer, Marv’s administrative their RNA substrates and to manipulate academic year of 2011/2012, living and assistant, keeps Marv writing, signing, their specificities for multiple purposes. working in central London. During that executing, declining and accepting on Deadenylases, such as human CNOT8, period, he wrote a substantial NIH grant, schedule – not to mention, correctly not only remove poly(A), but also repress which since has been funded; co-wrote – well, mostly. She keeps a mean and translation completely independent of a collection of papers with members effective calendar, and is a great shield as that activity. Since the same deadenylases of the lab; and continued to develop well. You cannot overestimate the value of are recruited by many different RNA- the programs he created that send UW good insulation. binding molecules, their mechanisms of undergrads to Cambridge and Oxford. At action are of central importance. the same time, he created new programs Departures… In addition to the humans and for Heidelberg and Barcelona. He also Amy Cooke has left for EMBL after molecules that live here, multiple became a balletomane, however contrary defending her thesis, and now is a post- creatures bright and beautiful join that may seem to his apparent agility and doc in Matthias Hentze’s group. Yvonne us in our cohabitation. Each species morphology. In December of 2012, Marv Koh now is a post-doc as well, working provides something special. The yeast,S. was thrilled to join his post-doc mentor, with Sydney Brenner in Singapore. Jacque cerevisiae, continues to permeate work John Gurdon, in Stockholm, for his Baca (now Legendre) lives in Livermore, in the lab, due to the ease with which receipt of the Nobel Prize – a wonderful California (near Berkeley) and is applying molecular genetics can be done. Most and unforgettable experience. Marv also for positions there. JJ Chritton lives of us at least have a dalliance with yeast; continues to teach the graduate class in near Madison and is working at Epic, some have full-fledged affairs, and try to Methods that he created, which he enjoys a prominent software company. Alana understand its networks of RNA control. tremendously, in large part because it Beadell moved to the University of A distant fungal relative, Neurospora, enables him to meet grad students and Chicago. Among our ex-undergrads, has recently joined us as well, provoked post-docs throughout the department Caitlin Bell graduated this past December by similar interests. The South African as they work to develop and give their and is now working at St. Mary’s hospital clawed toad, Xenopus laevis, provides lectures. For an update on Judith, you will in Madison, while Eric Mortensen is oocytes and embryos that can readily be have to look at her Letter from the Lab. finishing his BS this spring and applying injected to analyze the behavior of specific But lest you have any doubt whatsoever – for jobs at local biotech companies. molecules, and determine how they affect which you shouldn’t – we remain happily mRNAs. C. elegans, a small nematode and covalently linked. Zach, our son, In the lab, but hardly human… worm, provides powerful genetic and is now a third-year graduate student at Molecules and creatures from quite molecular analyses that we try to bring Cal Tech in Bob Grubbs’ group, doing different branches on the evolutionary to bear on molecules we love. To do so, synthetic organic chemistry. Amazing – he tree have found comfortable homes with we often collaborate with the Kimble lab, now writes papers and grants, gives talks – us. Three main families of molecules live which concentrates on this organism. At and seems to be thriving and enjoying it. in the lab. Some – the PUF proteins and the moment, we are not working with We are more than a little happy for him. certain nucleotidyl transferases – were Drosophila as we have in the past, but the And if you want to embarrass him, tell discovered here and have remained. They lure of its nervous system still beckons. him you read the nice essay about him in sometimes sit quietly in the corner, and And don’t be surprised if other creatures Cal Tech News (http://www.caltech.edu/ sometime stand boldly front and center; join us…. dreams are afoot in Marv’s content/beginning-life-science) or read but they always occupy our collective restless cortex…. one of his papers… cortex, drawing on our energy in a happy synergy. The PUF proteins have become a Wrapping up, a final human or two… There is not enough room here to share paradigm for proteins that bind and control Marv is pretty much the same – or what you all are doing, but we would very mRNAs. We continue to study how they at least so it seems to him. Since the last much like to keep in touch. Please do do so, and to use their remarkable scaffold Newsletter, he was elected to the American come and visit when you have a chance. for studies of molecular remodeling. Our Academy of Arts and Sciences, in the same Or at least drop a line and let us know aim is to use them manipulate RNAs by election that brought in Bob Dylan, Paul what you are up to…. Or, just maybe, we design. Certain nucleotidyl transferases, Simon and Helen Mirren. Bob, Paul and should contrive to all meet somewhere including poly(A) and poly(U) Helen were deeply disappointed that and have a darn good time together. polymerases, regulate RNAs through the Marv was unable to attend the induction

65 Faculty Email & Telephone Numbers

Rick Amasino...... [email protected] . . . .608-265-2170 If you have questions or information Aseem Ansari...... [email protected] . . . . .608-265-4690 please feel free to contact us. Alan Attie...... [email protected] . . . . . 608-262-1372 Sebastian Bednarek...... [email protected] . . . 608-263-0309 http://biochem.wisc.edu Sam Butcher...... [email protected] . . . .608-263-3890 Department of Biochemistry Margaret Clagett-Dame.... [email protected] . . . . .608-262-3450 University of Wisconsin–Madison Mike Cox ...... [email protected] ...... 608-262-1181 433 Babcock Drive Betty Craig...... ecraig@ facstaff.wisc.edu . . . . . 608-263-7105 Madison, WI 53706-1544 USA Brian Fox ...... [email protected] . . . . .608-262-9708 Paul Friesen ...... pfriesen@ facstaff.wisc.edu . . . . 608-262-7774 Phone: (608) 262-3040 Colleen Hayes...... [email protected] . . . . .608-263-6387 FAX: (608) 262-3453 Hazel Holden ...... [email protected] . .608-262-4988 Aaron Hoskins...... [email protected] ...... 608-890-3101 Alumni News Laura Kiessling...... [email protected] . . . . .608-262-0541 E-mail: [email protected] Judith Kimble ...... [email protected] ...... 608-262-6188 Bob Landick...... [email protected] . . . . 608-265-8475 John Markley...... [email protected] . . . . 608-263-9349 Change of Address, Information, Tom Martin...... [email protected] ...... 608-263-2427 and General Inquiries Julie Mitchell...... [email protected] . . . .608-263-6819 Sarah Saunders James Ntambi ...... [email protected] . . . . 608-265-3700 (608) 265-2507 David Pagliarini...... [email protected] ...... 608-890-3254 E-mail: [email protected] Ann Palmenberg...... acpalmen@ facstaff.wisc.edu . . . .608-262-7519 Wes Pike...... [email protected] . . . . . 608-262-8229 IPiB Graduate Program Ron Raines ...... [email protected] ...... 608-262-8588 (Information) John Ralph...... [email protected] ...... 608-890-2429 Ivan Rayment...... [email protected] . .608-262-0437 Kate Ryan (608) 265-2281 Tom Record...... [email protected] ...... 608-262-5332 E-mail: graduateadmissions@ biochem.wisc.edu Alessandro Senes...... [email protected] ...... 608-890-2584 Mike Sussman...... [email protected] ...... 608-262-8608 Doug Weibel...... [email protected] . . . . 608-890-1342 Undergraduate Program/Internships Marvin Wickens ...... [email protected] . . . .608-262-8007 James Hardy (608) 265-9846 Jill Wildonger ...... [email protected] ...... 608-890-4619 E-mail: undergraduateprogram@ biochem.wisc.edu Emeritus Gifts / Donations Julius Adler...... [email protected] ...... 608-262-3693 Laurens Anderson...... [email protected] . . . . 608-230-3319 Please use the form at the right Hector DeLuca...... [email protected] . . . . 608-262-1620 or go online to: Perry Frey...... [email protected] . . . . . 608-262-005 http://biochem.wisc.edu/ Dave Nelson...... [email protected] . . . . 608-263-6879 and click on "Make a Gift" George Phillips...... [email protected] ...... 713-348-6951 George Reed...... [email protected] . . . . . 608-262-0509 You may also contact the Chair: Bill Reznikoff...... [email protected] ...... Betty Craig Roland R. Rueckert...... [email protected] . . . . 608-262-6949 (608) 262-3040 Heinrich K. Schnoes...... 608-262-0650 E-mail: [email protected] John W. Suttie...... [email protected] . . . . .608-262-2247

66 Donors to Biochemistry Funds in 2011-12

Dr. Alan C. Aisenberg Dr. David E. Hamer Mr. Ralph T. Schwarz Dr. Walter M. Barker Dr. David A. Haugen Dr. & Mrs. Donald J. and Drs. Duane A. and Dr. Robert P. Hausinger and Ann R. Siehr Norma M. Benton Ms. Susan L. Kalvonjian Dr. Thomas J. Skatrud Dr. Roger E. Boldt Mr. Brian J. Konrad Professor & Mrs. Frederick G. and Professor James T. Bradley Dr. & Mrs. Mei-Chang and Ursula A. Smith Ms. Julie E. Brady Ann C. Kuo Dr. Pari D. N. Spolter Professor George E. Bunce Professor David O. Lambeth Dr. Anne B. Swanson Mr. & Mrs. Patrick L. and Dr. & Mrs. Eric S. and Dr. Richard C. Theuer Stacey J. Carney Rebecca C. Lightcap Ms. Nancy Torbet Dr. Samuel Y. Chan Dr. Arnold S. Loo Dr. James J. Vavra Professor Shiow-Her Chiou Dr. William D. Maxon, III Dr. Douglas E. Vollrath Dr. Scott T. Cooper Drs. Horace M. and Dr. Theodore R. Watson Dr. Julia M. Cox Arlene Mazzone Dr. William W. Wells Professor Jerry B. and Mr. & Mrs. John P. and Ms. Jessica Zinter Dr. Carole J. Dodgson Tashia F. Morgridge Mr. Vincenzo Franco and Dr. Yeh-Shan Peng Fisher Scientific Dr. Barbara Gerratana Mr. & Mrs. John C. and Lucigen Corporation Dr. Sandaruwan Geeganage Sara C. Pirnstill Promega Corporation Dr. & Mrs. Glen E. and Mr. Thomas C. Puerzer Lynn T. Gutzke Dr. Saul A. Schepartz

Department of Biochemistry Fund BCHEM

67 Nonprofit Org. U.S. Postage PAID Madison, WI 433 Babcock Drive Permit No. 658 Madison WI 53706-1544 USA Address correction requested