Transcript MCB Spring 2005 • Vol. 8, No. 1 Newsletter for Members and Alumni of the Department of Molecular & Cell Biology at the University of California, Berkeley

Gunther Stent, Generalist, Chromosome Feted at 80 Mystery Solved

Neurologist Oliver Sacks, chemist Manfred Few sights are as awe-inspiring as a cell in Eigen and biologist Sydney Brenner were anaphase. Seen through the microscope, the among the scientific notables who gathered replicated chromosomes, having lined up in Koshland Hall on a sunny April Saturday neatly along the midline of the dividing cell to celebrate the life and work of Professor like a row of tiny X’s, are simultaneously Emeritus Gunther Stent. The rare congress of yanked apart. Each X splits into two sideways luminaries and Nobel-prizewinners from V’s careening in opposite directions, folded diverse fields was intended to represent at the middle like a running back receiving a Stent’s wide-ranging interests and contribu- flying tackle. It all happens in the blink of an tions over the course of his career, which has eye in a space smaller than a speck of dust. lasted more than half a century. The orderly segregation of chromo- Organizers Michael Botchan and David somes is absolutely essential to ensure that Weisblat originally wanted the symposium to Gunther Stent every cell has a complete set of genes. Errors coincide with Stent’s 80th birthday last year, in segregation can sometimes lead to cancer but coordinating the visits of so many top sci- or birth defects. Yet how every cell pulls this entists proved more challenging than expect- influenced by physicist Erwin Schrödinger’s off without a hitch nearly every time is poor- ed, Botchan says. In the end, the April 9 book What is Life?, which suggested that ly understood. symposium featured seven speakers who undiscovered laws of physics might be neces- continued on page 4 . . spoke on subjects as diverse as genome sary to explain heredity. The book mentioned expression, free will and visual perception. Max Delbrück as a young physicist with Besides the many local friends, colleagues and interesting ideas along these lines. So Stent interested students who filled Cox wrote Delbrück to ask if he could join his lab Auditorium, former post-docs and graduate at the California Institute of Technology as a students of Stent’s turned up from around the postdoc. country. Throughout the day, Stent looked As Stent tells it today, he hardly knew radiant. “I was completely overwhelmed,” he what he was getting into. Delbrück was using said a week later in his office in LSA. bacteriophage to study the nature of genes, Stent was among the handful of pioneer- and when he offered the young Stent a posi- ing scientists whose work launched the disci- tion, he said: “Do you want to work on pline molecular biology after the second phage?” “Yes sir,” Stent replied, “that’s exactly world war. Having fled Nazi Germany in what I want to work on, but could you 1940, Stent went to school in Chicago and refresh my memory as to just what phage is later studied physical chemistry at the actually all about?” University of Illinois. But after graduate Collared: Dam1 rings bound to microtubules school, his interests turned to biology. Like (Courtesy of Stefan Westermann) many of his contemporaries, he was deeply continued on page 2 ...... Gunther Stent continued from page 1

Stent came to UC Berkeley as an he published more than 100 papers on the experiments of Oswald Avery, which demon- Assistant Biochemist in 1952, around which neurophysiology of the leech. strated DNA to be the genetic substance, as time DNA had just become generally accept- At the same time, Stent began to an example of premature science. Even ed as the chemical basis of heredity. At explore more deeply his longstanding inter- though in retrospect the implications of the Berkeley, he continued to study the nature of est in philosophical questions. He published experiment were clear, Stent argued it had genes and their expression through the use of articles such as “Molecular biology and little impact on genetics at the time and few DNA radio-labeling techniques in bacterio- metaphysics” (Nature 248, 779-781; 1974), people talked about its significance until phage and E. coli. He helped establish and and “Limits to the scientific understanding years later. But some scientists, including shape the Department of Virology in 1957 of man” (Science 187, 1052-1057; 1975). Nobel-prizewinning geneticist Joshua and the Department of Molecular Biology in Philosophical claims often provoke Lederberg, were annoyed by Stent’s article, 1964. He chaired that department from 1980 controversy, and Stent’s were no exception. saying they knew full well the implications of to 1986 and then served as the founding One article, “Prematurity and uniqueness in the work right away. The paper still touches chair of MCB, which subsumed molecular scientific discovery” (Sci Am. 227, 84-93; off philosophical arguments today, much to biology and biochemistry, until 1992. 1972), got him into hot water with col- Stent’s surprise. “I thought it was a simple In the late 1960’s, Stent’s interest began leagues because it described the classic 1944 point,” he says. to turn away from strictly molecular ques- tions. He had decided that the really com- pelling problems—such as the structure of DNA and the genetic code— had all been solved. As Brenner told the audience at the symposium, Stent liked to say at the time that “molecular biology has such a great future behind it.” What grabbed his interest was neuroscience, and over the next 20 years

Clockwise from top: Seymour Benzer and Gunther Stent during a break; Oliver Sacks prepares his talk; Dale Purves discusses the nature of vision with Jim Watson; Stent and Eric Wieschaus at lunch.

2 Philosophical differences were in evi- Other speakers included Princeton dence at the symposium as well. Noted University biologist Eric Wieshaus, who Berkeley philosophy professor John Searle, shared the 1995 Nobel Prize in Physiology or Ruthild Winkler-Oswatitsch, Manfred who has sparred with Stent on previous occa- Medicine for his work on embryonic devel- sions, devoted his talk to their disagreement opment, and Manfred Eigen from the Max over the nature of consciousness and free will. Planck Institute for Biophysical Chemistry in Eigen’s partner and frequent co-author, “The highest compliment one philosopher Göttingen and winner of the 1967 Nobel can pay another is to try to refute something Prize in Chemistry. Among the well-known took photographs throughout he says,” said Searle. “I’m now going to pay figures in the audience were science writer Gunther a compliment.” Horace Judson, author of The Eighth Day of The day’s wide-ranging and thought- Creation: Makers of the Revolution in Biology, the day and was kind enough to provide provoking talks, punctuated with humorous as well as James Watson and Seymour Benzer, anecdotes delivered in a roast-like manner, who, with Stent, were members of Delbrück’s copies to the Transcript. A sampling kept the audience well entertained. Brenner, “Phage Group” at Cold Spring Harbor Stent’s first postdoc in the early 1950’s and Laboratory in New York. winner of the 2002 Nobel Prize for his work The day was appreciated by young and appears below. on developmental genetics, discussed his old alike. “Biology in general should pay ideas about the relationship between more attention to his senior citizens,” said ‘genome’ and ‘phenome.’ Neurologist Oliver Professor Emeritus Harry Rubin. “It tends to Sacks, author of The Man Who Mistook His forget its history in the rush to be up to Wife for a Hat and Awakenings, described date.” At least on this day, history was clinical cases of brain lesions that suggest remembered. human consciousness is much more modular than it seems.

Clockwise from right: Stent unwinds at the end of the day with Manfred Eigen; John Searle delivers his critique of Stent's ideas on free will; Stent converses with his former postdoc (of 50 years ago) Sydney Brenner.

3 . . . Chromosomes continued from page 1

Now a group of MCB researchers led by chromosome hangs on has been one of the the 10 components and showed that they David Drubin, Eva Nogales and Georjana big mysteries.” could form rings around microtubules in a test Barnes has opened a window to one of the The first hint of a solution came in 1998 tube. In the electron microscope, these look most perplexing aspects of chromosome seg- with the discovery of a protein called Dam1, something like curtain rings around a rod (see regation. In a paper published in January, mutations in which either cause the spindles image on page 1). The rings stabilize the they describe a remarkable ring complex that to break down or produce defects in segrega- microtubules, and, perhaps most strikingly, are attaches the segregating chromosomes to the tion ( J Cell Biol. 143, 1029-1040; 1998). able to slide along them in a manner sugges- microtubule fibers that lead to opposite poles Later, Iain Cheeseman, a former graduate tive of the way the entire kinetochore may of the cell. The rings appear to slide along the student in the Drubin/Barnes lab, showed slide along the crumbling microtubule during microtubule, keeping the chromosome con- that Dam1 was part of a 10-member complex anaphase. nected even as the microtubule disintegrates needed for microtubules to attach to the Work is now continuing to show how the and shortens rapidly during anaphase. kinetochore (reviewed in J Cell Biol. Dam1 ring fits into the whole kinetochore. “When I first saw the pictures, I 157,199-203; 2002). Postdoc Stefan But already anyone who peers through a thought, ‘Wow’,” said BMB professor Jeremy Westermann, lead author of the new paper microscope at a dividing cell can have a much Thorner, “because I was convinced it was a (Molecular Cell 17, 277-290; 2005), purified clearer picture of what is likely to be going on. giant step in solving one of the long-standing puzzles about how chromosomes are faithful- ly segregated at each cell division.” The puzzle has to do with the nature of microtubules. These dynamic rods make up the spindle fibers which guide the two sets of replicated chromosomes to opposite sides of the cell. Microtubules of the spindle appara- tus connect to the chromosome via the kine- tochore, a massive complex of between 70 and 100 proteins. Yet the microtubules them- selves are continually growing and shrinking by adding and dropping subunits at both ends, making it hard to picture how the kine- tochore manages to stay attached. “There is continuous flux,” says Drubin. “How the From left: Nogales, Westermann, Drubin and Barnes MORGAN HARRIS DIES AT 88

MCB mourned the loss of Professor Emeritus in culture. This finding came at a time when Morgan Harris this semester. Known for both much of the effort in molecular biology was his rugged outdoorsmanship and his contri- focused on cloning individual genes for vari- butions to cell biology, Harris died of pneu- ous cell and organismal traits. By showing monia on February 14 at Kaiser Permanente that methylation of DNA could significantly Medical Center in Oakland. He was 88. alter a cell’s sensitivity to drugs, Harris “He was someone who did not go with became one of the first to recognize the the fashions,” said longtime friend and col- importance of epigenetic inheritance. league Harry Rubin. “He went with what he Harris also produced a classic volume on saw. He was a person of absolute integrity — the behavior of cells in culture. Published in granite solid.” 1964, Cell culture and somatic variation is still Scientifically, Harris was best known for used in some labs as a reference today. a series of experiments in the early 1980s In his earlier life, Harris was a pioneer- which showed that epigenetics can have a pro- ing rock climber in Yosemite. Together with found effect on the phenotype of cells grown frequent climbing partner David Brower, the Morgan Harris 4 FACULTY NEWS

Carolyn Bertozzi (HHMI, Chemistry and Judith Klinman (Chemistry and BMB) will The $5,000 award was granted in recognition of BMB) has been elected to the National be awarded an honorary Ph.D. from the Nogales’ pioneering work on the structure of Academy of Sciences. www.nas.ed University of Pennsylvania in the Spring of tubulin and the nature of its interaction with 2006. www.upenn.edu the cancer drug taxol. www.chabotspace.org Carlos Bustamante (HHMI, Physics and BMB) made a number of award lists this John Kuriyan (HHMI, Chemistry and George Oster (Environmental Science, Policy past year. They include the 2004 BMB) has received the 2005 Richard and Management and CDB) won the second Biophysical Society Founders Award, the Lounsbery Award from the National annual Emerson Center Lectureship Award 2004 Hans Neurath Award of the Protein Academy of Sciences “for his critical role in given by the Cherry L. Emerson Center for Society, the 2004 Alexander Hollander revealing the structural mechanisms Scientific Computing at Emory University. Award of the National Academy of underlying processivity in DNA replication www.emerson.emory.edu Sciences, the 2004 Southern Peru Copper and the regulation of tyrosine kinases and Corporation National Science Prize, and the their interacting target proteins.” Randy Schekman (HHMI and CDB) has 2005 Richtmyer Memorial Lecture Award received a Dr. honoris causa from the University from the American Association of Physics Michael Marletta (Chemistry and BMB) of Regensburg. www.uni-regensburg.de Teachers. Bustamante has pioneered tech- will become the Chair of the Department of niques for manipulating single molecules. Chemistry in July. chem.berkeley.edu Loy Volkman (Plant and Microbial Biology and alice.berkeley.edu BMB) will host Visiting Miller Professor Susan Marqusee (BMB) will host Visiting Kathryn Miller, who studies actin cytoskeletal Walter Freeman (Professor of the Graduate Miller Professor Carl Pabo, a structural biolo- proteins at Washington University in St. Louis. School) received the 2004 Distinguished gist who has made numerous contributions www.biology.wustl.edu/faculty/miller Service Award of the Knowledge to the understanding of how proteins bind to Engineering and Discovery Research DNA. Pabo is Chairman of the Scientific Institute at the Auckland University of Advisory Board of Sangamo BioSciences, Technology. www.kedri.info Inc., in Richmond, California. Marqusee was He is also the 2005 recipient of the Dactyl also elected Executive Council member of Foundation’s Annual Prize for applying the Protein Society. proteinsociety.org Science to Literature. www.dactyl.org Eva Nogales (HHMI and BMB) is the sec- Jack Kirsch (Chemistry and BMB) will be a ond recipient of the annual Chabot Science visiting professor at Uppsala University in Award, to be presented at the Chabot Space June. www.uu.se & Science Center’s Gala on June 25, 2005.

environmentalist and leader of the Sierra Harris is survived by his wife, Lola, of Club who died in 2000, Harris established Kensington, and two sons, Roger of Seattle 11 climbing routes in Yosemite Valley in the and Ronald of Ithaca, N.Y., both of whom 1930s. Famed nature photographer Ansel are also biologists. He is also survived by four Adams captured Harris and Brower reaching grandchildren. a summit in a photograph that later The family requests that, in lieu of appeared on the cover of an early climbing flowers, donations be sent to the Golden guide. In 1936, Harris and his fellow Gate Chapter of the Audubon Society, 2530 climbers pioneered the pendulum traverse, San Pablo Ave., Suite G, Berkeley, CA the use of a rope to swing from point to 94702-2047. point, during the first climb of Royal Arches. In all, Harris is credited with 14 first — portions adapted from an obituary by ascents in the valley and with establishing Robert Sanders, Media Relations the “Shaky Leg Crack” route on the east face of Mt. Whitney.

Morgan Harris climbing in Yosemite Valley 5 AWARD WINNERS

GRAD INSTRUCTORS WIN AWARDS

This year, 15 MCB instructors received the Outstanding Graduate Student Instructor Award.

Oron Frenkel Han Lu Catherine O’Connor (Health and Medical Sciences) (Bilder Lab) (Collins Lab)

Annaliese Beery (Neuroscience Grad Group)

Lindsay Garrenton Nicole Meyer-Morse Rachel Shreter (Thorner Lab) (Portnoy Lab) (Nogales Lab)

Raymond Chen (Thorner Lab)

Erin Green Sarah Munchel Jessica Shugart (Kaufman Lab) (Weis Lab) (Shastri Lab)

Benjamin Freedman (Heald Lab)

Katherine Harris Yuko Nakajima Peter Woodruff (Beckendorf Lab) (Drubin/Barnes Lab) (Bertozzi Lab)

6 CLASS NOTES

Derrick Brazill (PhD 1995) is an Assistant Thomas Cunningham (BA 2000) Is Chair of Back & Trauma Rehabilitation Professor in the Department of Biological working on his Ph.D. at the University of and Vice-Chair of Neurorehabilitation at Sciences at Hunter College in New York City. Illinois, Champaign. St. Mary’s Medical Center in San Francisco ([email protected]) where he runs both an inpatient rehabilita- Susan DeLong (BA 1999) is pursuing tion unit as well as an outpatient clinic. Elwyn Cabebe (BA 1992) is finishing his res- her masters and PhD in Environmental He says despite having trained at Stanford, idency in Internal Medicine at Santa Clara Engineering at the University of Texas, he has always been die-hard Cal fan at Valley Medical Center in San Jose. He will be Austin. Her research is related to bacterial heart. ([email protected]) a Hematology/Oncology Fellow at Stanford genetics and gene expression for pollutant starting in July 2005. He is married to a fel- degrading bacterial cultures in engineered Deepak Sarpangal (BA 2000) is an low MCB graduate, Emily Lim (1994). They pollutant treatment systems. MBA candidate at the Stanford Graduate have a one-year-old son, Isaiah. ([email protected]) School of Business. He is concurrently pursuing a Master’s in Education at the Yu Chin Christine Chen (BA 1996) received Alexandra Dusa (BA 2001) received her Stanford University School of Education. her Master’s in Public Health from the Master’s in Chemistry from UC Santa Previously, Sarpangal was an investment Columbia University Mailman School of Cruz in June 2004, and has begun banker and private equity investment Public Health (class of 1999). This year she is working towards a Ph.D. in Biomedical professional for Goldman Sachs in completing her M.D. at SUNY Syracuse, Sciences at the Université Catholique de Menlo Park, New York, and London. Upstate Medical University. Her residency Louvain in Brussels, Belgium. ([email protected]) will be in Obstetrics and Gynecology. In ([email protected]) 2003 and 2004, she was proud to serve as a Rommel Suratos (BA 1996) worked for National Vice President for the International Christine Fang (BA 1999) is a fourth- seven years at Chiron doing mammalian Federation of Medical Students’ Associations. year medical student at the University and microbial fermentation as well as At Berkeley, Chen was one of the first stu- of Utah and is planning to go into radia- protein refolding with the title of Specialist dents to participate in the Biology Scholars tion oncology. She will be married in the I/Pilot Plant Supervisor. He is currently Program (BSP) and the Ronald McNair spring of 2005. working at Genentech in South San Scholars Program. She says she attributes her ([email protected]) Francisco where he has been involved in academic and research success to the “solid manufacturing technical transfers to the education” she received from her Berkeley Justin Liu (BA 1995) completed his company’s plant in Spain. At Cal, he was MCB major. Chen welcomes email from residency in Physical Medicine & the Drum Major of the Cal Band in 1994. classmates and her former faculty mentors. Rehabilitation at Stanford University He is now the proud father of a nine- ([email protected]) Medical Center in June 2004. He is now month-old boy. ([email protected])

CLASS NOTES WANTS TO HEAR FROM YOU

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7 AWARD WINNERS

UNDERGRADUATE AWARDS Transcript Department of Molecular & Cell Biology Divisions of Cell & Developmental MCB Biology and Neurobiology Departmental Citation: Huiyi Chen (Bertozzi Lab) Chaikoff Memorial Awards The MCB Transcript is published twice Outstanding Scholar: Brandon Beamer (Calendar Lab) a year by the Department of Molecular and Cell Jamie Harrington Biology at the University of California, Berkeley. Caterina Equinozio (Firestone Lab) (Andrew Jackson Lab, PMB) DESIGNER: Betsy Joyce Kentson Lam (Harland Lab) Jamie Harrington EDITOR: Jonathan Knight (Andrew Jackson Lab, PMB) Division of Biochemistry & MCB Newsletter Gunjan Pantangay (Forte Lab) University of California Molecular Biology Department of Molecular and Cell Biology Jeffrey Huang 142 Life Sciences Addition #3200 Grace Fimognari Memorial Prize (Brian Staskawicz Lab, PMB) Berkeley, CA 94720-3200 Aaron Lay (Bilder Lab) Tsang Lau (Bob Buchanan Lab, PMB) [email protected] Kazuo Gerald Yanaba & Daniel Lo (Firestone Lab) Ting Jung Memorial Prize Send address changes to: May T. Cho David Nguyen (Martin Lab) Alumni Records (Priscilla Cooper Lab, LBNL) 2440 Bancroft Way May Wong University of California (Brian Staskawicz Lab, PMB) Berkeley, CA 94720-4200 Division of Genetics & Development Ian Kratter (T. Don Tilley Lab, Or e-mail [email protected] Spencer W. Brown Award Chemistry) Current and past issues of the newsletter are Frederick Ling (Beckendorf Lab) Zhenwen Tina Tan (Winer Lab) available on the MCB web site (http://mcb.berkeley.edu/news). Division of Immunology Wendy W. Wong (Dan Lab)

Outstanding Undergraduate Calvin Hang (Gregory Aponte Lab, Nutritional Science and Toxicology)

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