Transcript MCB FALL 2008 • VOL. 11, NO. 2 Newsletter for Members and Alumni of the Department of Molecular & Cell Biology at the University of California, Berkeley

FROM MICRO RNAs TO STAR-NOSED MOLES: THE RESEARCH OF THE NEW MCB FACULTY

Bautista completed her postdoc in ATOUCHINGTALE ’s lab at UCSF, where the first temperature-sensitive pain receptor, trpv1, was identified as the target for capsaicin, the If you have never experience the odd sensa- burning, hot molecule from chili peppers. tions of Szechuan peppercorns, go try them This receptor is one of many pain and touch now. Crunch a few of the reddish pods in receptors that allow sematosensory neurons your teeth and let them rest in your mouth. detect environmental stimuli such as tem- You’ll feel your tongue go numb, and, a few perature, pressure, and chemical irritation. seconds later, you’ll taste something Capsaicin from chili peppers is able to peppery and lemony. Soon you’ll sense both bind sites on trvp1 that would normally be cool and hot temperatures and feel an triggered by an endogenous molecule. unusual tingling, buzzing sensation. What This ability to hijack the system protects the gives Szechuan peppercorns such strange plants: most mammals will find the heat- Assistant Professor Diana Bautista effects? New MCB Assistant Professor inducing sensation of capsaicin unpleasant Diana Bautista is figuring it out. and quickly learn to avoid eating peppers. Despite their central importance to our quality of life, we don’t know much about the molecular mechanisms of touch and pain. How are pain thresholds set? At what point does a light touch begin to hurt? And why do these thresholds sometimes not reset? How do we learn special touch sensitivity, such as reading Braille? The answers could lead to an under- standing of—and treatments for—such condi- tions as chronic pain or pain insensitivity. In Julius’s lab, Bautista studied another pain receptor, , which is sensitive to . She noticed that most of the receptors being studied were pain receptors, even though about half of the sematosensory neurons are dedicated to sensing light touch. In her own lab, Bautista is identifying touch receptors through studying spices and herbal remedies. “I really liked David Julius’s

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approach,” says Bautista. “In my own lab, “This is the world’s most sensitive and after that I was totally hooked.” She I thought I could apply a lot of the same touch organ,” says Bautista, while showing researched visual system in Drosophila, and approaches to understanding touch trans- a movie of the moles gobbling up pieces of changed her focus to signal transduction duction.” earthworm at lightning speeds. “The nose mechanisms during her graduate studies at It’s been working. From Szechuan is really small, but innervated ten times Stanford with Rich Lewis. She went back to peppercorns, used traditionally to numb more than the human hand. Think about our sensory systems for her postdoctoral work at toothaches, she identified several members ability to read Braille, and this small organ UCSF. of the KCNK channel family that may play an is much more sensitive.” She is happy to continue living in the important role in the detection of light touch. While the mole’s star has similar types Bay Area, where she takes advantage of its [Nature Neuroscience 11, 772 - 779 (2008)]. of neurons as other mammals have, its cultural and natural offerings. When she’s Bautista’s lab is currently deciphering percentage of pain and touch receptors is not in lab, you may find her in Chinatown, the molecular mechanisms of these remarkable: the star has 95% touch enjoying a traditional meal with a palate- channels and investigating how hydroxy- receptors. buzzing dose of Szechuan peppercorns. alpha-sanshool, the compound from Preliminary work demonstrated that Szechuan peppercorns, can lead to pain the same basic neural structures in the relief. She is also continuing to test other mole’s star and human skin are the same, TINY RNAs WITH plants to find new types of touch receptors. but the mole has them in much higher To look at cellular mechanisms of densities. Bautista plans to discover basic HUGE POTENTIAL touch, Bautista is developing systems to molecules and mechanisms involved in mechanically stimulate different types of touch sensitivity by identifying the types of touch-sensitive neurons in culture. For molecules that are enriched in the mole’s You may think those small RNA molecules example, stretching neurons grown on elas- star versus skin cells of other mammals. couldn’t possibly be important, so you let tic membranes can mimic the stretch of Having arrived in January, Bautista them run off the end of your gel. New MCB skin. Low amounts of stretch stimulate light says she is enjoying her Berkeley experi- Assistant Professor Lin He might advise you touch receptors, but stretch the membrane ence so far. “I love the campus, and I love not to do that. Her recent findings suggest further and pain fibers will fire. Using this the department,” she says. “The depart- that you may be missing something diagnostic, she may find genes and mole- ment is so diverse. It’s great to be exposed interesting. cules that mediate touch transduction in vivo. to a lot of different approaches and ques- Lin He works on micro RNAs (miRNAs), Rounding out her approach, Bautista tions, and I think it helps you come up with which are so named because of their tiny aims to recruit the star-nosed mole as an creative ways to address the question that size, usually about 20-24 nucleotides. Still, animal model for touch receptors. These you are interested in.” they pack a punch. In that short length, they blind moles have 22 fleshy protrusions, Diversity is a theme for Bautista, who fold into a secondary structure and imper- collectively termed the “star,” around their draws on a history of diverse scientific fectly match messenger RNAs to effectively noses that allow the moles to quickly find experiences and interests. regulate gene expression. food, such as earthworms, by texture. “I went to University of Oregon to study miRNAs were first discovered in 1993 “It looks like a weird starfish,” says Bautista. environmental science and ecology,” says in C. elegans, by Victor Ambros and Gary And it does. Bautista. “But I took a neuroscience class Ruvkun, using classic genetics screens. Because no homologues were found in other animals, they were assumed to be a worm quirk. But, seven years later, when researchers started screening other animals, they found the miRNAs everywhere. “To everyone’s surprise, there’s a huge repertoire of these RNAs in almost all model organisms,” says He. Almost 500 miRNAs are identified in humans. He and others believe that studying this newly discovered, abundant class of genes will shed light on how and when gene expression is regulated. miRNAs recognize their targets by imperfect base pairing. This trick allows one miRNA to target multiple genes, resulting in the post-transcriptional regulation of a fleet of genes at the same time. It’s thought that these targeted messenger RNAs become sequestered in the processing body in the cytoplasm and then can undergo partial degradation, in a similar pathway to RNAi- induced degradation. The sequestered Assistant Professor Lin He

2 mRNAs may also be re-released and trans- age. She participated in special programs for lated into proteins. school children who excelled in these sub- “We are really at the very beginning of jects. She fondly remembers solving puzzles understanding the realm of non-coding in the weekly math camp. Through these RNA,” says He. “These small RNAs provide a programs she developed a love for experi- nice entry point for us to probe the function mentation and, especially, chemistry. of non-coding RNAs and how they interact Her high school biology teacher is with coding genes to achieve very complicat- responsible for turning her interest to living ed regulation of gene expression.” systems. As an undergrad in China, she Furthermore, miRNAs seem to play a majored in biology, where she studied basic regulatory role in human tumor formation molecular biology. and tumor maintenance. A number of As a graduate student at Stanford miRNAs are located in regions of the University, she focused on genetics. Her genome that show alteration, such as ampli- thesis research involved classic mouse fications, deletions, or translocations, in genetics experiments, working on coat color Assistant Professor Andreas Martin human cancer cells. Micro RNAs also show genes with Greg Barsh. “I always liked changes in expression patterns in tumor genetics because it sparks a lot of intellectual versus normal human cells and/or tissues: thinking and it often presents really interest- To degrade misfolded, damaged, or some miRNAs are depleted while others are ing problems that need a lot of deciphering,” unneeded proteins, cells employ molecular enhanced. she says. machines that transform the chemical energy He’s lab is researching the function of He started working on miRNAs as a side stored in ATP into mechanical work aimed at miRNAs involved in human cancer using ani- project during her postdoc in Gregory unfolding proteins and making them accessi- mal tumor models and cell culture systems. Hannon’s RNAi-focused lab at Cold Spring ble to degradation by a protease. Martin is They are focusing on a miRNA that has a Harbor. interested in how these unfoldases recognize very high expression in B cell lymphoma “I did a side project on miRNA.” Says He. a target and how they channel energy for cells versus control cells. Putting this micro “I took several miRNA genes that was over- unfolding. RNA into a mouse model confirmed that the expressed in cancer and I put it into a mouse As a postdoc in Bob Sauer’s lab at MIT, miRNA is oncogenic, the first miRNA impli- tumor model. To my great surprise, it worked Martin worked on the bacterial ClpXP system, cated in tumorgenisity [Nature (2005) much better than some of the protein which is composed of an unfoldase (ClpX) and 435:828-33]. It turns out that this is not an oncogenes that I was planning to work on. a peptidase (ClpP). ClpX uses energy from isolated case, many more miRNAs have now I immediately was fascinated by the fact that ATP to unfold proteins and feed them into a been found that are important for many you can put in such a small RNA species into degradation chamber of ClpP. Martin’s work types of tumors. an animal tumor model and have a tumor- covered substrate recognition, unfolding, He is also interested in tumor suppres- genic activity comparable to some of the translocation, and the mechanisms of ATP sor miRNAs, which can suppress tumor famous known protein oncogenes.” hydrolysis. formation and/or maintenance. Her team Almost five years later, He is still Martin’s research led to a deeper under- identified a key miRNA component in the p53 fascinated by the interesting puzzles miRNA standing of the mechanical aspects of this pathway and is currently uncovering how it provides—and these small RNAs are likely to molecular machine. For instance, he found works at the molecular level. keep her occupied for years to come. that the six ATPase subunits in ClpX, which He’s lab will continue to screen for he likens to six cylinders in an engine, novel miRNAs that either promote or sup- contribute additively to degradation activity press tumor formation and growth in various BREAKING IT DOWN by hydrolyzing ATP and changing their model systems. conformation one at a time, but not necessar- “I would not be surprised if miRNA ily sequentially. Additionally, mutating certain functions are involved in almost all aspects The protein folding problem is famous: residues in the central pore that loosen the of developmental and physiological process- how does a string of residues find its one unfoldase’s grip on a substrate polypeptide es,” says He. “It’s a really big family of functional, stable 3D shape out of a stagger- increases the amount of ATP consumed. genes. I’m sure that that there are a lot ingly large set of possible confirmations? “It’s like making the gas mileage worse, more to be discovered.” New MCB assistant professor Andreas Martin like if you have a slipping clutch or transmis- Viewing the broader picture, He would was intrigued by this question as a graduate sion.” says Martin. “We use a lot of these like to understand how the unique proper- student, studying the folding kinetics and the machine analogies to explain these molecular ties of miRNAs affect their function, making thermodynamic stability of proteins. More motors.” them so adept at their regulatory tasks. recently, Martin’s attention turned to a differ- After unpacking the boxes in his new lab Beyond basic science, there may be applica- ent, yet related problem: how do cells break in MCB, Martin will focus on the 26S protea- tion for miRNAs to diagnostic or therapeutic down these stable structures when they are some from eukaryotes, a more complicated uses for tumors, since they are natural, no longer needed? unfolding and degrading machine. Like the small, and relatively easy to deliver. “My main focus was on protein folding,” ClpXP system, it has two parts. The 19S Lin He grew up in China where she says Martin. “Then I switched to destroying unfoldase subcomplex recognizes appropri- enjoyed math and science from a very early them.” ate substrates, unfolds them, and feeds the

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polypeptides into a 20S peptidase for degra- dation. Unlike the ClpXP system that has just two different proteins forming the two parts, the proteasome has at least 32 different subunits. Adding to the complexity, the pro- teasome system integrates a large number of associated proteins that are active for instance in substrate delivery. The proteasome recognizes its targets through a polyubiquitin tag, added in a three step process by other enzymes. The story is a bit more complicated, though, since the proteasome must often prioritize its efforts to degrade some proteins before others, although each have a polyubiquitin tag. Also, some proteins must only be clipped or partially degraded, and not completely Associate Professor Henk Roelink destroyed. In some cases these functions may be regulated by associated adaptors, in other cases intrinsic features of the sub- 19S cap or its subunits to address the ques- To answer this question, Roelink is strate polypeptide may be responsible. tion of how the unfoldase machine works. using a bottom-up approach to understand The unfoldase part of the proteasome Because the proteasome’s ATPases the early fundamental processes that are threads the unfolded protein through a cen- belong to the large family of AAA+ enzymes likely to take place reiteratively throughout tral pore. Some protein sequences, such as that are active for instance in helicases, development. He is studying differentiation those containing glycine-alanine repeats, chaperones, and motor proteins, under- in the neural tube, the developmental may be slippery or unable to be threaded, standing their detailed mechanisms may precursor to an animal’s nervous system. causing the translocation process to stop. also give important insight into operating The neural tube begins as a homoge- Some viruses use this feature to their principles of other molecular machines. neous sheet of cells that acquires differ- advantage, coding for protein sequences that When exploring protein unfolding, ences along its various axes, allowing the are resistant to proteasome degradation. Martin draws upon his experiences in pro- region that develops into the head to be “Many groups are working on the pro- tein folding as a graduate student in Franz different than that which develops into the teasome, but most of them focus on more Schmid’s lab in Germany. “In enzymatic tail, for example. Roelink is interested in cell biological aspects.” Says Martin. “A lot of protein unfolding and processing, the same understanding how signal molecules, components of the ubiquitin-proteasome rules apply as in protein folding,” he says. which come from adjacent sources, cause system have been identified, but the detailed Martin says he has always been the differentiation. “It’s a very interesting, molecular mechanisms are largely unknown. interested in science and biochemistry in but very complex phenomena,” he says. I want to use biochemical approaches to particular. “Biochemistry was the right The young neural tube cells can understand the mechanisms of substrate choice for me because you can describe measure the concentration of signaling recognition, how ATP is utilized to exert biological processes in quantitative detail, molecules present and acquire a pheno- unfolding forces, and how substrate is with equations,” says Martin. type based on that concentration. In translocated.” When not exploring the inner workings essence, the cell can count how many of Martin is attacking these problems from of molecular machines, Martin likes to be its signal receptors are occupied. Roelink’s several angles. active through sports, cross-country and favorite signaling molecule Sonic “First, I will primarily focus on in-vitro downhill skiing, snowboarding, biking, and, Hedgehog (Shh) is a protein involved in biochemistry using purified components,” most recently, kite surfing. many developmental processes, including says Martin. He’ll use the proteasome from neural tube patterning. yeast as the model system, because it is “We’re trying to find out how cells relatively easy to manipulate, purify and NERVE BEGINNINGS can read a distinct concentration and dif- handle, and it has high homology to the ferentiate accordingly,” says Roelink. “An mammalian systems. He will also develop an equally big problem is that we don’t even “Nature works in very clever ways,” says E. coli expression system, which will allow know how this molecule that’s released new MCB Associate Professor Henk Roelink, proteasome mutations that would be lethal to from the notochord gets far away into the clearly delighted by the prospect of solving eukaryotic cells. epithelium. It’s a very difficult question its puzzles. Spectroscopy will allow real-time because the signal Sonic Hedgehog is “I’d like to understand how an embryo measurements of substrate degradation and non-soluble and membrane bound, so you develops and how information contained in a ATP utilization. Single molecule FRET exper- would not expect it to travel 10 or 15 cell genome and an egg leads to an organism iments, for instance, can detect conforma- diameters away. But it does.” that is thinking and walking around,” says tional changes within the protease or the While signaling molecules were Roelink. “It’s a very big question.” substrate. Martin will also pursue the deter- thought to travel via simple diffusion, mination of high-resolution structures of the CONTINUED ON PAGE 8. . . 4 FACULTY NEWS

M Rachel Brem received a 2008 New Scholar M David Drubin received the Ira Herskowitz I UC Berkeley Extension named David Presti Award in Aging by the Ellison Medical Award at the Genetics Society of America/ an Honored Instructor for his exceptional Foundation for her work in signaling Yeast Genetics and Molecular Biology and inspiring teaching. behaviors of the unfolded protein response meeting last summer in Toronto, Canada. in aging. I Randy Schekman was appointed the first Senior Fellow of the UC Berkeley Miller Institute. This five year appointment is awarded to accomplished tenured faculty members at a rate of about one per year. It comes with an annual $50,000 in discretionary research funds. The Miller Institute website states: “The appointment of Randy Schekman illustrates the high standard that we seek for Senior Fellows. Randy's scientific stature and citizenry on I Richard Harland was elected President- campus and around world are well known M Beth Burnside received the Berkeley elect of the Society for Developmental and admired.” Citation from the Chancellor for her con- Biology. tributions as Vice Chancellor for Research. I Robert Tjian was elected as the new I Lin He was awarded a New Faculty Award president of the Howard Hughes Medical from the California Institute for Institute. (See story below.) Regenerative Medicine (CIRM), the state’s stem cell research funding program. I Russell Vance received an Investigatorship from the Cancer Research Institute. This I The December 2008 issue of Discover provides funds to study inflammasome magazine features Nicole King as one of activation in Naip5-deficient mice. the “Best Brains in Science.” The article describes the research of 20 scientists I Gerald Westheimer was elected to an under the age of 40. honorary membership of the Royal Society of New South Wales, the oldest academy of I The Protein Society has awarded Jamie I John Kuriyan received the American science in Australia. He is a long-time Doudna Cate their 2008 Irving Sigal Young Society for Biochemistry and Molecular Fellow of the Royal Society of London. Investigator Award, which is given to an Biology (ASBMB)’s 2009 Merck Award, early career scientist who has contributed which recognizes outstanding contributions to protein research. to research in biochemistry and molecular biology. He was also elected to the American Academy of Arts and Sciences.

TJIAN TO HEAD HOWARD HUGHES MEDICAL INSTITUTE

MCB Professor Bob Tjian is the newly elected have in terms of helping set the direction president of the Howard Hughes Medical and policy of the educational and research Institute. HHMI, a private organization with an program in the United States, and probably endowment of $17.5 billion, supports the internationally." Tjian has been an investigator with HHMI for biomedical research of more than 350 investi- 20 years and a professor at UC Berkeley gators at over 60 universities and other Tjian will assume this position on April 1, since 1979. Born in Hong Kong, his research organizations throughout the United 2009, succeeding Nobel Laureate Thomas distinguished career includes a B.S. in bio- States. The MCB department hosts ten R. Cech of the University of Colorado at chemistry from UC Berkeley in 1971, a Ph.D. HHMI-supported faculty members. Boulder. Tjian will continue to run his MCB from Harvard University in 1976, and post- lab, taking a portion of his research with doctoral work with Nobel Laureate James "It's an exciting opportunity," says Tjian. him to Janelia farm, HHMI’s research Watson at Cold Spring Harbor Laboratory. "I think that the head of HHMI is one of the campus in Ashburn, Virginia. most influential positions that a scientist can 5 2007-2008 GRADUATES

FALL 2007

I Sonia Bakkour (Sha) Characterization of I Tiffany Juarez (Raulet) Roles of the I Jerod Ptacin (Bustamante) Mechanism of ICOS-mediated B7h shedding NKG2D receptor and its ligands in tumor DNA transfer by the FtsK/SpoIIIE family of I Veysel Berk (Cate) Towards a model for surveillance and autoimmunity DNA translocases ribosomal decoding I Leonard Kusdra (Martin) Multiple roles of I Daniel Serna (Raulet) Murine I Jacob Corn (Berger) Structure and src family kinases in mammary epithelial cytomegalovirus evasion of natural cell function of the bacterial primase tumorigenesis. surveillance I Maria Divina Deato (Tjian) Switching core I Kevin Larimore (Sha) Selective initiation I Zejuan Sheng (Kramer) Synaptic Ca2+ promotor recognition complexes during and control of antibody responses by and information coding in vertebrate rods myogenic differentiation dendritic cell and B cell mediated ICOS and cones I Todd Ferreira (Ngai) Characterization Signaling I Jessica Shugart (Shastri) Exploration of of the development of the zebrafish I Hanson Lee (Isacoff) Alternative splicing diverse antigen processing pathways that olfactory system of neuroligin-1 regulates the rate of generate peptides for presentation by I Andrew Greenstein (Alber) Structure, pre-synaptic differentiation MHC I molecules function, and regulation of eukaryotic-like I Venkataramanan Nandagopal (Eisen) I Jamin Willoughby (Firestone) Artemisinin serine/threonine protein kinases in Experimental and computational analyses regulation of proliferation and disruption Mycobacterium tuberculosis of early embryonic cis-regulatory of androgen responsiveness of human I Katie Gustavsen (Gallant) Effects of elements in the diptera prostate cancer cells attention on the responses of V4 neurons

SPRING 2008

I Jennifer Beh (Levine) Early heart I Deirdre Lyons (Weisblat) Mechanisms I Ansley Scott (Zusman) Receptor development gene networks and controlling the asymmetric second methylation controls single cell and group morphogenesis in the Clona intestinalis cleavage of the Helobdella embryo behaviors in the social bacterium chordate tadpole I David Mets (Meyer) Meiotic crossover Myxococcus xanthus I Emily Cadera (Schlissel) Regulation of position and frequency are regulated by I Scott Siera (Cline) Positive regulation of receptor editing by NF-kB chromosome structure in C. elegans sex-lethal in the germline and soma of I Megan Clarey (Botchan/Nogales) I Yongkai Ow (Shastri) Cryptic translation Drosophila melanogaster Structural studies of the Drosophila origin in immune surveillance under stress I Aakanksha Singhvi (Garriga) Asymmetric recognition complex I Raj Pai (Cate) Structural studies of the cell divisions and cell fate specification in I Emily Derbyshire (Marletta) interaction of ribosome recycling factor C. elegans neural development Investigating the heme environment and with the ribosome I Fai Yiu Siu (Doudna) The role of 4.5S RNA mechanism of activation of soluble I Brant Peterson (Eisen/Levine) in the E. coli SRP system guanylate cyclase Harnessing natural sequence variation I Christopher Toret (Drubin) I Nathaniel Echols (Alber) Molecular to explore cis-regulatory function and Comprehensive analysis of clathrin/actin mechanisms of ser/thr kinase regulation evolution mediated endocytosis in S. cerevisiae in Mycobacterium tuburculosis I Mark Price (Marletta) Investigation into a I Michael Whang (Raulet) A novel NKG2D I Aaron Garnett (Amacher/Eisen) T-box novel two component signaling pathway ligand expressed in the skin activates transcriptional factors in zebrafish in Shewanella oneidensis MR-1 skin yδ T cells mesoderm development I Adam Schindler (Schekman) ATF6 I Tracy Young (Marqusee) Investigation of I Liana Lareau (Brenner) Unproductive transport from the endoplasmic the biophysical properties responsible mRNA splicing and ultraconserved DNA reticulum to the golgi during the unfolded for differences in the energy landscapes elements protein response of homologous mesophilic phospho- I Twyla Lombana (Alber) Structural and I Mark Schramp (Martin) The requirement glycerate kinases functional characterization of the for ERK5 in src-induced morphological regulation of PknB, an essential transformation serine/threonine protein kinase of Mycobacterium tuberculosis 6 CLASS NOTES

I Sarah L. Gaffen [PhD 1994] has moved I Gor McCarter [PhD 1996] is an Assistant I Geoffrey Wool [BA 2002] received a PhD in from SUNY Buffalo to an Associate Professor of Biological Sciences and newly Pathology from the University of Chicago Professor position at the University of appointed Assistant Dean for Student in August 2008. He is returning to the Pittsburgh, Dept. of Medicine, Division of Services for the College of Pharmacy, third year of medical school at Chicago Rheumatology & Clinical Immunology. Touro University - California in Vallejo, CA. and hopes to be back in the Bay Area in She’d love to hear from classmates. ([email protected]) 2010. “Go Bears!” ([email protected]) ([email protected]) I Jason Ng [BA 1998] completed a Doctor of I Michael Galvez [BA 2004] finished his Optometry degree in 2003 and then spent pre-clinical years at a year practicing optometry before return- School of Medicine, and is now doing a year ing to UCB to complete a PhD in the of full-time research as a Howard Hughes Optometry School in 2008. Currently, he is Medical Institute Medical Research an Assistant Professor at the Southern Training Fellow in the Department of California College of Optometry. Surgery. ([email protected]) ([email protected])

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7 professor Bob Tjian’s lab to decipher details embryo. the much more complex environment of an the stem cell system, they will be tested in Once interesting phenomena are found via Roelink isn’t throwing out the eggs quite yet. such long distances can be addressed. question of how signaling molecules travel molecules. Through these systems, the genotypes for testing a variety of signaling different systems of different cell types and limiting factor. And it is no more.” the tissue we worked with was always the riches,” says Roelink. “Even three years ago mouse genetics. it allows application of the vast library of hand-harvesting cells from chick embryos, more efficient than the previous method of and signaling. Not only is this method much These can be used to study Shh movement tissue that resembles early neural tube cells. Roelink to turn embryonic stem cells into a types. cell which can lead to differentiation into multiple what it was passed, a gradient is formed, of fraction a passes cell each If cell. to cell single source would be passed along from transport molecules. actively to opportunity ample allow yet free diffusion inhibit would which together, epithelium, cells are packed very tightly brane to membrane between cells. In the active “bucket brigade” transport from mem- Roelink argues that there must be an CONTINUED FROM PAGE 4. . . Berkeley, CA 94720-3200 142 Life Sciences Addition Department of Molecular and Cell Biology University of California at Berkeley MCB Roelink will also collaborate with MCB Even with the cell culture method, Roelink sees potential to develop many “It feels like an embarrassment of Signaling molecules originating at a A recent breakthrough has enabled 12133NEWSL ADDRESS SERVICE REQUESTED Newsletter now local romance. long-distance, once a and professors, fellow the broad biological research interests of his about his new home: the scientific amenities, hard place to leave, Roelink appreciates much a is Seattle that year. acknowledging While Shh-induced cancers and as a laboratory tool. is currently used therapeutically for Indeed, cyclopamine blocks Shh signaling and mutants often had a single midline eye. Roelink remembers thinking, since Shh something to do with Sonic Hedgehog,” cyclopia. ed cyclopamine, a small molecule that causes of Washington in Seattle. There he investigat- who cloned the Shh gene. of several scientists one at different institutions was he when period” “crazy a remembers inducing molecules in the neural tube. He Jessell to learn how to measure the effects of position at Columbia University with Tom Amsterdam, Roelink started a postdoctoral Stanford and defending his thesis in neural tube. patterns of expression in the genes he identified, which had interesting interested in the normal functions of the became He genes. causing tumor find to mammary cells in mice by using retroviruses 1990. He worked on tumorigenesis in and moved to Stanford Medical School in Netherlands Cancer Institute in Amsterdam during his graduate work, which started at the Netherlands. He came to the United States differentiation. of transcriptional changes occurring in neural He arrived in Berkeley at the start of the “Well if it causes cyclopia, it must have Roelink started a laboratory at University After finishing his graduate work at Roelink is originally from the complex as an organism.” an as complex it’s something simple as a car engine or “I like to know how things work, whether “I have a rational mind,” says Roelink. that involve a technological component. activities such as scuba diving and flying adventurous enjoys He hobbies. many too MCB 142 Life Sciences Addition #3200 Department of Molecular and Cell Biology University of California MCB Newsletter BetsyDESIGN: Joyce RavenPRODUCTION: Hanna Berkeley. Cell Biology at the University of California, a year by the Department of Molecular and The MCB Transcript is published twice (http://mcb.berkeley.edu/news). are available on the MCB web site Current and past issues of the newsletter Or e-mail [email protected] Berkeley, CA 94720-4200 University of California 2440 Bancroft Way Alumni Records Send address changes to: [email protected] Berkeley, CA 94720-3200 Roelink describes himself as having University of California U.S. Postage PAID Non-profit Org. Transcript