AT BERKELEY MCB SPRING 1998 Newsletter for Members and Alumni of the Department of Molecular & Cell Biology at the University of California, Berkeley

Graduate Admissions Committee, under the We were all greatly saddened by the loss Message from academic and administrative leadership of of our dear friend and colleague, Marian David Drubin and Eileen Bell, has enrolled a Koshland (see page 4-5). Marian represented new class of 45 students, 10 of whom have the best of citizenship and scholarship here at the Chair independent fellowships (NSF, HHMI, Cal and in the larger academic arena. She DOD, and University). Congratulations to continued to teach, supervise research, and I hope you enjoy our inaugural edition of the the faculty and student members of the serve as Head of the Graduate Affairs Unit MCB at Berkeley Newsletter. MCB was born Graduate Admissions Committee and the even as she labored in declining health. I must almost ten years ago, and we have grown to Graduate Affairs Unit staff for another out- recount a personal anecdote concerning my such an extent that I felt it was necessary to standing year. Although it is premature to initial encounter with Marian. The Koshland’s create a vehicle of communication connecting make a public announcement, we have every invited me to a party at their home shortly the Divisions of our far-flung enterprise. In indication that our faculty recruitment for after I arrived in Berkeley in 1976. The addition, we have trained a generation of stu- 1998-99 will also be a smash- Biochemistry Department had dents and fellows who have gone on to their ing success. As of this writ- just returned from its annual own careers and who may be interested in the ing, it appears that we will Asilomar retreat where Dan current affairs of our Department. We intend secure 4 or 5 new faculty, and I had enjoyed our first to publish the Newsletter once a semester to each one the top choice of encounter of the humorous provide a survey of the Department’s student the relevant faculty search kind on stage in front of our and faculty research and training activities that committees. Our success in colleagues. Marian’s first words have made this Department the largest acade- recruiting comes, in part, to me were: “Dan tells me mic unit on campus. This first issue covers the from the enthusiasm we you’re funny; OK, Schekman, news from the 1997-98 academic year. communicate to our prospec- make me laugh!” I knew from Among the highlights of the year are the tive students and faculty. that moment that Marian significant honors and achievements that our Thanks to all who have would expect nothing less than students and faculty have garnered (see pages pitched in. precision in my science and 9-12). Also, MCB is expanding its interactions I particularly wish to acknowledge my my humor! We remember her fondly, and with other departments on campus. Two of predecessors, Co-Chairs John Gerhart and applaud the decision of our campus adminis- the new MCB faculty have joint appointments Alex Glazer and before them Gunther Stent, tration to rename the Bioscience and Natural (see pages 2-3), and MCB is leading the effort who led the Department through the worst Resources Library in her honor. to establish a Center for Neuroscience which days of the California recession. Each year Finally, I want to thank Laura Williams, will unite faculty from various departments of their term brought a shrinking state budget our Newsletter editor. Laura is a PhD graduate (see page 8). and a declining faculty census brought of ours from the Kane/Chamberlin lab who We have had a tremendous year recruit- about by early retirements. In spite of these has decided to make a career in scientific ing graduate students and new faculty. Our limiting financial and personnel resources, publishing. Laura gained experience as the they managed to staff courses and provide editor of the Women in Cell Biology column administrative services for an increased under- in the American Society for Cell Biology graduate enrollment and for an expanding Newsletter. I am certain that her efforts here MCB at Berkeley is a publication of the Department of Molecular and Cell Biology effort to secure extramural support. Now will set high standards for future MCB at at the University of California, Berkeley. that the recession is over and the State and Berkeley Newsletters. EDITOR: Laura Williams the University are being more generous with Have a good summer. DESIGN: Betsy Joyce resources, I look back with respect at the Send comments and questions to ability of John, Alex, and Gunther not only RANDY SCHEKMAN [email protected] (e-mail) to keep us afloat, but to allow us to prosper as MCB Co-Chair a department. NEW FACULTY

Rebecca Heald, CDB

Rebecca Heald became an Assistant the assembly of bipolar mitotic Professor of Molecular and Cell spindles in Xenopus egg James Berger, BMB Biology in July, 1997. extracts. These results showed that spindle assembly can James Berger will join the Future Projects at Berkeley: Education: occur in the absence of centro- Biochemistry and Molecular My lab will continue in these • B.A. in Chemistry, 1985, somes or kinetochores. I also Biology Division as an Assistant areas, studying the structure Hamilton College, Clinton, NY. showed that spindle pole for- Professor on July 1, 1998. He and function of enzymes and • Ph.D., 1993, Harvard Medical mation was dependent on the is currently a Fellow at the enzyme complexes involved in School, Thesis Advisor: Frank microtubule-based motor, Whitehead Institute at MIT. replication and chromosome McKeon. cytoplasmic dynein, both in structure. • Thesis project: I identified phos- the presence and absence of Education: phorylation sites in the nuclear centrosomes, but that centro- • B.S. in Biology, 1990, Why are you excited about lamin proteins that when somes, when present, consti- University of Utah. working at Berkeley? Berkeley mutated prevent nuclear lamina tute dominant sites for spindle • Ph.D., 1995, Harvard offers the opportunity to inter- breakdown in mitosis. These pole assembly. University, Thesis Advisors: act with students and faculty results showed that phosphory- James C. Wang and Stephen in numerous and diverse areas lation just outside of the large Current Projects: I am follow- C. Harrison. of science, all within an envi- coiled-coil domain controls the ing up on my postdoctoral • Thesis Project: My thesis ronment known for scientific assembly dynamics of these project to study mitotic spindle involved using X-ray crystal- excellence. intermediate filament-type pro- assembly. We would like to lography to determine the teins. I also showed that overex- identify proteins on mitotic three-dimensional structure What is the most rewarding pression of positive cell cycle chromatin that stabilize micro- of a type II DNA topoiso- achievement in your career regulatory proteins could cause tubules. We would also like to merase, an enzyme that so far? Determining the struc- premature entry into mitosis in reconstitute kinetochore func- untangles and unknots DNA ture of a protein. The process the absence of complete DNA tion on beads. in the cell. The structure is similar to building a jigsaw replication and that this could provided a molecular model puzzle in three dimensions, be rescued by overexpression of Why are you excited to be for demonstrating how the and it yields a vast amount of a negative regulator. These working at Berkeley? enzyme can physically trans- biochemical information about results showed that cell cycle There are so many interesting port one DNA through a protein’s function in a short progression in vertebrate cells is people and projects; the place is another. time. regulated by a balance between both diverse and friendly. positive and negative regulators, Current Project: While a Personal information: just as in yeast. What is the most rewarding Fellow at the Whitehead Married to Marian Feldman achievement in your career Institute, the focus of my who will graduate this June Postdoc: so far? It has been extremely work has been to understand with a Ph.D. in Art History • 1993-97, European Molecular rewarding to get the lab started the structural basis by which from Harvard. Biology Laboratory (EMBL), and to have students to interact proteins convert cellular ener- Heidelberg, Germany, with and to teach. gy into motion and work. In American Cancer Society particular, we study enzymes Postdoctoral Fellowship, Personal information: I enjoy that unwind, move, and Advisor: Eric Karsenti. bicycling, reading, and music. manipulate DNA and RNA in • Project: I developed a system in the cell. which plasmid DNA-coated beads were sufficient to induce 2 Carlos Bustamante, BMB

Carlos Bustamante will begin a joint appointment as a Professor of Dan Portnoy, BMB Biochemistry and Molecular Biology and Physics on July 1, 1998. He is currently a Professor at the Current Projects: I started University of Oregon where he has working on the intracellular been since 1991. From 1982 to bacterial pathogen Listeria Dan Portnoy is a Professor of 1990, he was on the faculty of the monocytogenes in 1986 after my University of New Mexico. first time, the potential energy Biochemistry and Molecular Biology, postdoc, and I have been ever function of globular proteins. In and he has a joint appointment since. I view L. monocytogenes as Education: addition, we will be investigating with the School of Public Health. In the bacteriophage Lambda of the behavior of DNA and RNA July, 1997, he moved his lab from • B.S. in Biology, 1973, intracellular pathogens. We are Universidad Peruana Cayetano polymerases as molecular motors the University of Pennsylvania analyzing every detail of the by using laser tweezers. Finally, we where he was in the Department Heredia, Peru. intracellular life style of this • M.S. in Biochemistry, 1975, will continue the development of Microbiology since 1988. Before organism which, surprisingly, and application of the Scanning that he had been a faculty member Universidad Nacional Mayor de only needs five proteins to San Marcos. Force Microscope (SFM) to inves- at Washington University in St. escape from a vacuole, exploit a tigate multiprotein-DNA com- Louis from 1986 to 1988. • Ph.D. in Biophysics, 1981, UC host system of actin-based Berkeley, Thesis Advisor: Ignacio plexes involved in transcription motility and spread cell-to-cell. regulation both in prokaryotes Education: Tinoco, Jr. and eukaryotes. • B.A. in Bacteriology, 1978, • Thesis Project: Two effects were Why are you excited about known previously in the optical University of California, Los working at Berkeley? Why are you excited about Angeles. activity of chiral (handed) mole- • The commitment to graduate cules: circular dichroism and working at Berkeley? I am • Ph.D. in Microbiology & education. excited by the enthusiasm and Immunology, 1983, University optical rotatory dispersion. We • The commitment to first-rate, characterized a third effect, i.e., drive for research that one finds of Washington, Seattle, Thesis cutting edge science among everywhere at Berkeley and by Advisor: Stanley Falkow. the ability of chiral molecules to my colleagues. scatter the two circular polariza- the unlimited potential for new • Thesis Project: We discovered that • The breadth and diversity of collaborations. a plasmid shared by all patho- tions with different efficiency in science in the department and all directions of space. genic Yersiniae (including Yersina on campus. What are the benefits of your pestis, the causative agent of joint appointment both to you • The opportunity to be part Postdoc: bubonic plague) encoded a num- and to the departments? of the rebirth of microbial • 1981-82, Lawrence Berkeley ber of secreted proteins (Yops) Tapping into the knowledge and biology on campus. Laboratory, Advisors: Marcos F. which were essential for viru- expertise from faculty in both Maestre and Ignacio Tinoco, Jr. lence. Years later, it became clear departments will be an enormous What are the benefits of your • Project: We built an instrument that many other animal and plant benefit to our research program. joint appointment both to you to measure circular differential pathogens also secrete Yops In addition, I will be able to inter- and to the departments? scattering, and we made the first directly into their host cells. act with and to train students The benefits of the joint direct measurement of this effect with two widely different back- appointment are that I can bring on nuclei of sperm cells. This Postdoc: grounds. I believe that there is a together groups of scientists and method has since been used to • 1983-86, Rockefeller University, trend in biology towards quantifi- students who previously did not discriminate between different Damon Runyon Walter Winchell cation and that, in the near interact. To do this, I have orga- pathogenic and non-pathogenic Cancer Fund Fellowship and future, biology students will need nized a well-attended seminar bacteria. NIAID National Research series in Microbial Biology, and more training in the physical sci- Service Award, Advisor: Jay ences in order to make their I am starting a new course on Selected Awards and Honors: Unkeless. bacterial pathogenesis. impact in research. • Project: We cloned and charac- • Elected Fellow of American Physical Society, 1995. terized a lysosomal protease, What is the most rewarding What is the most rewarding cathepsin L, and a macrophage • Howard Hughes Medical achievement in your career so achievement in your career so Institute Investigator, 1994. Fc Receptor. One key aspect of far? Watching the development far? I feel that most of the satis- my training is that I went from • Alfred P. Sloan Fellow, 1985. faction in scientific work is in the of systems I initiated. I started • Searle Scholar, 1984. the premiere bacterial patho- both the Yersinia and Listeria act of research itself, in the quest genesis lab (Falkow’s) to a lab systems from scratch. It is very for that which we do not under- dedicated to aspects of the host. Current and Future Projects: stand. Because the latter is a con- gratifying to see the Listeria At Berkeley, we will continue system develop as one of the stantly moving target, perhaps the Selected Awards and Honors: developing the methods of single best answer to this question is ‘that premiere systems for the study molecule manipulation that we • Eli Lilly Award in Microbiology of the actin-based cytoskeleton. which we are doing right now.’ and Immunology, 1996. started at the University of Oregon. In particular, we want to Personal Information: My wife, • MERIT Award from NIAID, Personal Information: My wife investigate the mechanical folding Silvia, is a speech pathologist. We NIH, 1995. is Suzanne Jacks Portnoy. She and unfolding of single protein have two kids, Fernanda (18 yrs.) s staying home to raise our molecules to try to map, for the and Carlos Jr. (15 yrs.). My main 2-year-old daughter, Eleanor. interests outside science are 3 history, music, and soccer. Remembering MARIAN KOSHLAND

1921-1997

MCB Professor of Immunology Marian Elliott Koshland died on October 28, 1997. Her career at UC Berkeley spanned 32 years. She came to Berkeley in 1965 as a researcher and a lecturer, and she joined the faculty in 1970. She later served as Chair of the Department of Microbiology and Immunology and, until the time of her death, was the Head of the MCB Graduate Affairs Office. In recognition of her distinguished service to the campus and outstanding achievements in her field, Marian Koshland was posthumously awarded the Berkeley Citation, the University’s highest honor. Professor Koshland is survived by her husband of 52 years, MCB Professor Daniel E. Koshland, Jr., five children, and nine grandchildren. She is remembered here in the words of her students and of her colleague, Jim Allison.

Memories of

Jeff Wallin was Marian Koshland’s last Her Students graduate student and is still in MCB working toward his Ph.D. Up to a week before she passed away, they were working on a paper Marcy Blackman (PhD, ‘85), a former which was published in a recent issue of graduate student of Marian Koshland’s Donations in Marian Koshland’s Science (March 20, 1998). Jeff has these and now an Associate Member in the thoughts: “As a mentor, Marian listened to memory may be sent to the Immunology Department at St. Jude’s my ideas about my project and let me Children’s Research Hospital in approach it my way, but she knew what help Graduate Fund, University of Memphis, shares her memories: “I was to give me in order to advance the project. California at Berkeley, Department in Marian’s lab when she came back Over time, I became more of an independent from a sabbatical in David Baltimore’s thinker. As a scientist, her longevity alone of Molecular and Cell Biology, lab at MIT. She turned the lab around is impressive, but her landmark discoveries with the new molecular techniques she 597 Life Sciences Addition #3200, were so seminal that they are taken for had learned, and it was an exciting place granted today.” When asked what he will Berkeley, CA 94720-3200. to be. Marian was in her late 50’s, but I remember about her, he replied: “People say remember Marian saying that she felt she was worldly and she loved art, but what I Checks should be made payable to like a postdoc again. Such enthusiasm will remember is her love for sports. She the UC Regents. for science was characteristic of Marian, could talk about sports as well as anybody I and it rubbed off on those around her.” have known.”

Blackman, Wallin, and Allison participated in the “The Status of Women Symposium: Mechanisms of Immune Regulation” dedicated to the memory of Marian Koshland at the Annual Meeting of the American Association of Immunologists in San Francisco on April 21, 1998.

4 MARIAN KOSHLAND putting a very high emphasis on experimental rigor and absolute scientific integrity. She was not affected by fads in science, but only in Remarks of a Colleague the bottom line that should be of interest to all scientists—how well hypotheses hold up to hard experimental scrutiny. Speaking for myself, and I suspect for MCB Professor of Immunology James Allison had a clear memory of the time in medical many of her fellows and students, I can gave the following remarks about Marian school when he first read Marian’s papers in attest to her quickness to challenge weak, (Bunny) Koshland’s impressive scientific career this area, and that it was for him a defining half-baked ideas. I can also attest to the at her memorial service at the University Art moment that motivated him to embark on a fact that she was willing to make helpful Museum on December 1, 1997. career in immunology. suggestions—once an idea passed her test, By the 70’s, Marian had returned to her you could be more confident in presenting Good evening. My name is Jim Allison. I am studies of secreted vs. serum-borne antibod- it to the wider community. an Immunologist who has known of Bunny’s ies. She identified a novel antibody subunit In honor of all of her accomplishments, work since I became an immunologist, and called the J chain, characterized it, showed Marian received awards that are much too knew her as a friend and colleague since she that it played a central role in antibody numerous for me to itemize completely. recruited me to Berkeley in 1985. I would assembly and secretion, and that the begin- She was, of course, elected to the National like to make a few comments on her contri- ning of its expression marked a clear, discrete Academy of Sciences, the American butions to our field. step in the maturation of B cells. This work Association of Arts and Sciences, and the It would not be at all an exaggeration led to the central theme of the remainder of Council of the American Association of to say that Bunny’s career as a scientist was her scientific career—understanding the way Immunologists, of which she served as spectacular. She made very important contri- in which a B cell becomes an active player in President in 1982-83. She served on many butions to our understanding of the immune the immune response. committees involved in setting national sci- system in every decade for the past half In the late 1970’s, she did a sabbatical entific policy. She was noted for her courage century. In the 1940’s, she studied the devel- stay in David Baltimore’s lab at MIT to learn and straightforwardness in speaking her opment of immunity to Asiatic cholera. Not molecular biology, as she felt that the future mind, and for her honorable positions on only was the information she obtained used of the field lay in this area. While at MIT, she emerging issues. in the development of vaccines, but, by the collaborated in obtaining the gene encoding Another area for which Marian was early 1950’s, Bunny had shown that secreted the J chain, and she brought the gene and her much admired was her status as a role model and serum-borne forms of antibodies were knowledge of this new technology back to for women. In addition to being a pioneer for discrete molecules. This was considerably Berkeley. In the 1980’s, she turned her atten- women in science in a field that was clearly before the formal definition of antibody tion to regulation of transcription of the J dominated by men during the early stages classes. chain gene by B cell growth factors. By the of her career, she also demonstrated that a By the 1960s, Bunny began to address 1990’s, her work had extended to the more woman could have a spectacular career while one of the central problems in immunology— general area of events that accompany and successfully managing to raise a family. It is the origin of antibody specificity. There was a direct B cell activation and maturation. In in part for this achievement that she will be raging debate between instructive models, an invited talk at the national meeting of the honored by the Committee for the Status of which held that antibody proteins were all American Association of Immunologists this Women in Science at a special symposium to the same and just folded around their target past February, she presented a wonderful be held at the upcoming Annual Meeting of antigens, and selective models, which argued description of recent work from her lab. They the American Association of Immunologists. that they were the products of different cells. demonstrated that the action of a transcrip- Reading back over some of Marian’s Bunny, in the early 60’s, published a series tion factor, BSAP, was very complex and works recently, I noted that in a memoir she of papers showing that the chemical composi- dynamic, and that it could have both positive stated that she chose science as a career tion of antibodies directed against different and negative effects—extinguishing some because of her conviction that it is a way of antigens were in fact different, thus arguing genes whose products were no longer needed making a lasting contribution, and, in a for selection. Legend has it that at the annual while turning on new genes with roles impor- sense, is immortal. The legacy that Marian meeting of the American Association of tant to the emerging antibody-producing arm has left us is in many ways immortal, in terms Immunology where she first presented her of the immune system. This talk was a mar- of her own scientific achievements, those of data, her talk was received by a standing ova- vel, and it put together complex biochemical the students and the fellows that she has tion—quite high praise indeed. By the end of phenomena in an understandable context of trained, and those of her colleagues like the 60’s, her work had become part of the biological function. It was a testament not myself on whom she had a strong and lasting mainstream of an emerging idea that is now only to the quality and timeliness of her own influence. For these things, she will long be one of the cornerstones of immunology, that work, but also to how far the field has come remembered and honored. is that antigen receptors, both of T cells and in a detailed understanding of the workings B cells, are encoded by multiple rearranging of the immune system in the half century gene segments. Bunny’s work in this area was since Marian entered it. Editor’s Note: I highly recommend Marian seminal. Charlie Janeway, who is currently If there is any single feature that marked Koshland’s illuminating and inspiring mem- the president of the American Association of Bunny’s work, it was this ability to reduce oir entitled, “Sheer Luck Made Me an Immunologists, recently commented that he complex phenomena to experimentally Immunologist,” published in Annual Reviews addressable components. She did this by of Immunology (1996) 14: ix-xv. 5 RESEARCH HIGHLIGHTS

Ellen Robey Gary Firestone Assistant Professor of Immunology

Professor of Cell and Developmental Biology Ellen Robey’s lab is elucidating the role of the Notch receptor in immune cell fate decisions. Gary Firestone’s group has discovered that indole-3-carbinol (I3C), a chemical which occurs A T cell precursor has two possible fates: it naturally in broccoli and other Brassica vegetables, inhibits the growth of cultured human may become a killer T cell which fights viral breast cancer cells. Specifically, I3C inhibits the expression of cyclin-dependent kinase-6 infections or a helper T cell involved in an (CDK6) and causes a G1 cell cycle arrest. The project was a collaboration with fellow UC antibody response. If the antigen receptor Berkeley Professor Leonard Bjeldanes in the Department of Nutritional Sciences. expressed by a T cell precursor recognizes a These effects of I3C on the cell cycle were found to be MHC Class I ligand, then the precursor cell independent of estrogen receptor signaling, although becomes a killer T cell. But if, instead, its I3C and related compounds are known to have anti- antigen receptor recognizes a MHC Class II estrogenic effects. Conversely, it was found that the ligand, then the precursor cell becomes a breast cancer drug tamoxifen, which is dependent helper T cell. on estrogen receptor signaling, has no effect on From nematodes to humans, the cell CDK6 expression. Finally, a combination of surface receptor Notch is involved in differ- I3C and tamoxifen was found to inhibit cell entiation and cell fate decisions. Since Notch growth more efficiently than either one alone, is present on immune precursor cells, Robey consistent with the different modes of action of investigated whether it might be involved in each agent. T cell lineage choice. These results suggest that, theoretically, a Robey’s team made transgenic mice with combination therapy with I3C and tamoxifen a constitutively active Notch receptor. They may be highly effective in breast cancer patients found that precursor cells become killer T with estrogen-responsive tumors. Two-thirds of cells, regardless of the ligand recognized by patients with metastatic breast cancer have estrogen- the antigen receptor. In other words, cells responsive tumors, but only half of those respond to that normally would become helper T cells tamoxifen therapy. Thus, only one-third of patients initial- become killer T cells. Robey explains, “The ly respond to tamoxifen, and those who do will eventually develop constitutive Notch receptor is overriding the tamoxifen resistance. In combination with I3C, lower doses of tamoxifen could, in theory, normal recognition, suggesting that it is act- be used to avoid tamoxifen resistance and to lessen its side effects ing downstream of the antigen receptor to I3C alone is promising as a cancer drug because it has no reported side effects, and it control cell fate determination.” Normally, has been shown to be a chemopreventative agent in rodents. Firestone sees a potential role the Notch receptor is present, but not active, for I3C as a post-surgical treatment to prevent tumor regrowth or new tumors. Firestone in cells destined to be helper T cells. Thus, points out, “What’s especially nice about this research is that one doesn’t have to be a vision- the presence or absence of Notch ligands may ary to see the potential for human health.” be regulating Notch signaling. They have But as a cell biologist and molecular endocrinologist, Firestone is interested in how I3C identified some Notch ligands and are now works at the cellular and molecular level. Firestone suggests that I3C may bind a target trying to figure out how they are regulated in receptor which then affects the transcription of a network of genes including the gene for the thymus. CDK6. His model is based on steroid receptors and their signaling, a subject he has studied for years. REFERENCES: E.A. Robey, D. Chang, A. Itano, D. Cado, H. REFERENCE: Alexander, D. Lans, G. Weinmaster, and P. Salmon C.M. Cover, S.J. Hsieh, S.H. Tran, G. Hallden, G.S. Kim, L.F. Bjeldanes, and G.L. Firestone (1998) Journal of (1996) Cell 87 (3): 483-492. Biological Chemistry 273(7): 3838-3847. T. Washburn, E. Schweighoffer, T. Gridley, D. Chang, B.J. Fowlkes, D. Cado, P. Salmon, and E. Robey (1997) Cell 88 (6): 833-843.

6 Udi Isacoff Paul Kaufman

Assistant Professor of Neurobiology Adjunct Assistant Professor of Biochemistry and Molecular Biology

Udi Isacoff’s lab has developed powerful In the two years that Paul Kaufman has been at Berkeley, he has expanded his investigation of new fluorescence techniques for studying chromatin assembly which he began as a postdoctoral fellow. In Bruce Stillman’s lab at Cold the ion channels that control excitability and Spring Harbor, Kaufman characterized human chromatin assembly factor 1 (CAF-1), which synaptic transmission in the nervous system, performs the first step in chromatin assembly, depositing histones H3 and H4 onto DNA. and, in the process, has found wider applica- Genes encoding the three subunits of CAF-1 have been cloned from human cells, and, for tions for the techniques. Isacoff’s group used the purpose of genetic analysis, from yeast cells. The three yeast genes are collectively referred to site-specific fluorescent labeling of the as CAC (Chromatin Assembly Complex) genes. Interestingly, the mammalian in vitro assay was Shaker potassium channel protein in combi- used to purify and clone CAF-1 from S. cerevisiae, demonstrating a lack of species specificity. nation with voltage-clamping to observe the The CAC genes are not essential for cell viability, but deletion of any of the CAC genes conformational changes induced by gating, reduces position-dependent transcriptional silencing. Since chromatin proteins are involved in that is opening and closing of the channel. this silencing, these results suggest that CAF-1 affects chromatin structure in vivo. As the labeled domain of the channel moves, Since the CAC genes are not essential, Kaufman reasons that they are either auxiliary play- the fluorescence changes because a fluo- ers in chromatin assembly or are functionally redundant, and he has evidence for the latter. His rophore is sensitive to its local environment. group has observed that mutations in several genes implicated in transcriptional regulation have Recently, they have begun an effort to use strong synthetic gene silencing defects when combined with cac mutations. “Perhaps severe similar optical fluorescence techniques to phenotypes are only observed when multiple pillars holding up the structure are knocked out,” observe structural events in single channels, Kaufman analogizes. “These synthetic interactions with other genes suggest that our strategy rather than in populations of channels. for finding other players in chromatin assembly is a good one,” and synthetic lethality screens In addition to providing structural are in progress. information, fluorescently labeled voltage- sensitive channels can optically report elec- REFERENCE: trical activity. In a cell, labeled channels can P. Kaufman, R. Kobayashi, and B. Stillman (1997) Genes and Development 11: 345-357 be used to noninvasively measure the volt- age across the membrane. Isacoff describes this as “harnessing signaling proteins and having them tell you when they are active.” Donald Rio When making such optical measure- ments in neural tissue, however, it is diffi- Professor of Genetics cult to measure the signal from only the cells of interest, for instance, the neurons Donald Rio is studying the mechanism and regulation of Drosophila P-element transposition and and not the glia. To solve this problem, finding similarities with other nucleic acid rearrangements, such as those that occur during Isacoff’s group designed “a voltage sensor immunoglobulin and T-cell receptor gene V(D)J recombination in the vertebrate immune encoded into DNA” which, when placed system. Transposons are mobile genetic elements which are present in many organisms, and the under the control of various promoters, Drosophila P element is one of the best characterized eukaryotic transposons. P-element transpo- could be targeted to specific cell types as sition occurs by a cut-and-paste mechanism initiated with cleavage by the P-element-encoded well as developmental stages, tissues, and transposase and followed by DNA repair by nonhomologous end joining involving host proteins. subcellular compartments. To do this, they Rio’s group has found that the repair of the double-strand DNA breaks formed in the made use of the green fluorescent protein process of transposition involves DNA-dependent protein kinase (DNA-PK), a nuclear serine- (GFP) which was originally isolated from a threonine kinase. They have shown that mutations in one of the three subunits of DNA-PK jellyfish. By fusing GFP to the Shaker potas- result in large deletions and chromosome loss due to defective repair at P-element-induced sium channel, they made an intrinsically breaks. Similarly in mice, mutations in another subunit of DNA-PK, the product of the scid fluorescent protein. Voltage-dependent (severe combined immunodeficiency) locus, cause defects in end processing and joining during gating of this chimeric channel causes large V(D)J recombination. Scid mice are immunodeficient because they have very few undifferentiat- changes in its fluorescence. Thus, they ed B or T cells. In both transposition and V(D)J recombination, DNA-PK mutations lead to created an optical probe to measure trans- unrepaired double-strand breaks which may result in deletions, chromosome loss, and cell death. membrane voltage which, since it is geneti- Because of the severe consequences of unrepaired double-strand DNA breaks, transposition cally encoded, can be selectively expressed is carefully regulated. Recent work in Rio’s lab has shown that DNA-PK may play a direct role in and localized. Isacoff has begun collaborat- that regulation. They have found that P-element transposase is a substrate for DNA-PK and that ing with other MCB labs to make similar the phosphorylation state of transposase affects its activity. optical sensors by fusing GFP to different Rio explains that the role of phosphorylation of transposase by DNA-PK may be to restrict channels and to other detector proteins transposition to the G2 phase in the cell cycle when DNA-PK and other repair machinery is such as receptors. expressed so as not to leave unrepaired double-strand breaks. “The implication is clear,” he says, “Signal transduction involving DNA-PK connects the cleavage event to the repair event. It may REFERENCES: also act to transduce extracellular stimuli to trigger DNA rearrangements.” He concludes, L.M. Mannuzzo, M.M. Morrone, and E.Y. Isacoff “Transposition is advantageous in terms of genome evolution because it introduces genetic (1996) Science 271: 213-216. variation, yet it can’t be so unrestricted as to cause cell death.” M.S, Siegel and E.Y. Isacoff (1997) Neuron 19: 735-741. K. Zito, R.D. Fetter, C.S. Goodman, and E.Y. Isacoff REFERENCES: (1997) Neuron 19: 1007-1016. E.L. Beall and D.C. Rio (1996) Genes & Development 10: 921-933. E.L. Beall and D.C. Rio (1997) Genes & Development 11: 2137-2151. E.L. Beall and D.C. Rio (1998) EMBO Journal 17: 2122-2136. 7 THE NEUROSCIENCE CENTER

An effort to create a Center for Neuroscience at UC Berkeley is being Physics, and Integrative Biology. As for graduate students, the Graduate Program in led by MCB Neurobiology Professors Corey Goodman and Carla Neuroscience, which was active before the departmental reorganization, will be reacti- Shatz. They provided their perspective on the development of the vated once the Center is under way. While waiting for the Neuroscience Neuroscience Center and an update on its current status. Center to get off the ground, we have already begun to build a strong campus-wide neuro- science community based on the strength of We began working on the Neuroscience the Neurobiology Division in MCB. We Center in April of 1993. In its initial concep- invite all members of the campus-wide com- tion, it was called the “Neuroscience munity to our divisional retreat each year. Initiative,” and it specifically proposed a Similarly, we encourage other neuroscientists fund-raising initiative to allow neuroscience to suggest and to host speakers in our semi- research on campus to expand in directions nar series. Finally, we invite representatives that MCB alone would not go, that is the from other areas of neuroscience to come to integrative, systems, cognitive, and computa- our faculty meetings. tional ends of the field. The same vision for a We have received tremendous support broad-based neuroscience program drives the from the neuroscience community across Neuroscience Center. Understanding how the campus, from MCB and other departments, human brain gets put together during devel- and from the administration, and, in the last opment, how it works to control behavior and year or so, the Neuroscience Center has perception, and how it changes with learning begun to take shape. A search for a director is and memory will require marshaling a broad under way, and a promising candidate has range of technologies and approaches. been identified. The University has made a From the outset, we thought that MCB commitment for four to six new faculty posi- was doing a terrific job of hiring young mole- tions for the Center. The administration has cular and cellular neurobiologists in not only also begun formal discussions about where to the Neurobiology Division, but also in CDB house the Center. Finally, the Center has and Genetics. However, we were concerned received two endowments. The Rauch family that no single department or unit on campus has endowed the Rauch Chair in memory was making the same kind of effort at the of their son Evan, who was an undergraduate systems and cognitive end of the field. at UC Berkeley. The other endowment is Moreover, we believed that the most innova- from Helen Wills Moody Roark, a Cal tive work in the field was going to be interdis- alumnus and a tennis legend who won ciplinary and at the interface of traditional Wimbledon eight times. She left her entire definitions. We wanted a home—a Center— estate to the University in the name of the that fostered interactions amongst neuroscien- Neuroscience Center because she was inter- tists from across the campus. Thus, sprang the ested in biology, especially of the brain. notion of the Neuroscience Center. At this point, we are convinced that The initial members of the Neuroscience Berkeley is poised to build the top neuro- Center will be the current members of the science program in the country. And after all, Graduate Group in Neuroscience, which con- although we may be a bit biased, understand- sists of faculty from MCB, Psychology, Vision ing the brain will be one of the great chal- Science, Environmental Science, Chemistry, lenges for science in the twenty-first century.

8 Outstanding GSI AWARD WINNERS

This year, the seven MCB students shown received Outstanding Graduate Student Instructor Awards along with the follow- ing students from other departments who taught MCB classes: Carrie Cowan and Cynthia Waters from Plant and Microbial Biology; Christine Eckels from Integrative Julie Hollien, Marquesee Lab, for MCB 110L Biochemistry & Molecular Biology; Paul Woo from the Endo- Biology Laboratory crinology Graduate Group; Ashild Vik from the Biophysics Graduate Group, Chai-Sue Lee, Jenny Way, and Kimberly Pothier from Health and Medical Heather Dawes, Meyer Lab, Sciences. for MCB 140 Genetics The winners were selected from the 151 graduate student instructors in Molecular and Cell Biology during the 1997 calendar year. The selections are Pak Ming Lau, Bentley Lab, made by MCB Divisional GSI Advisors for MCB 160L Neurobiology Laboratory with the concurrence of the Divisional faculty and are based on student and instructor evaluations. The GSI Advisors have noted that these GSIs performed at a very high level that was clearly a cut above Ben Eaton, Moore Lab, our other GSIs who, as a whole, are dedi- for MCB 130 Cell Biology cated teachers. Winners received certificates of dis- tinction from the campus GSI Teaching and Resource Center, and a reception was David Stellwagen, Shatz Lab, for MCB 160L Neurobiology Laboratory held in their honor at the Alumni House on May 7, 1998. Winners may submit an application for a Teaching Effectiveness Award which is designed to recognize exceptional teaching methods and includes a cash prize. Theresa Ho, Goodman Lab, for MCB 160 Neurobiology

Patricia Valdez, Robey Lab, for MCB 150L Molecular Immunology Laboratory 9 Undergraduate AWARD WINNERS

DIVISION AWARDS In recognition of outstanding achievements by MCB undergraduates, the following awards will be presented by the MCB Department Jill Licht wins the BMB Divisional Citation Catharina Fu wins the Henke Award during the MCB Commencement Ceremony This Divisional Citation represents the highest This award is made possible through the gen- achievement each year by a graduating senior erosity of the friends and family of James Henke, at the Greek Theater on May 25, 1998. The in the BMB Division, not only in terms of a neurobiology student who graduated in 1991. overall grade point average, but in major course- This award is given in recognition of outstand- following award descriptions are from the work, quality of research, and other such factors ing achievement in the neurobiology emphasis. MCB Undergraduate Handbook. that indicate promise of great success in the Recipients receive $200 and a certificate. student’s career. The winner receives $500 and a certificate. I.L. Chaikoff Award Winners

Haidy Lee wins the F.H. Carpenter Harry Chang Laurence Lu Memorial Prize in Biochemistry Matthew Chang Timothy Kubow DEPARTMENTAL Sumana Jothi Kavita Patankar This prize, made possible by the generosity of Wei Liu Eric Williams the family and friends of the late Professor CITATION Frederick H. Carpenter, is awarded annually to Dr. Chaikoff was a Professor of Physiology the outstanding junior MCB major in the whose area of expertise was thyroid function Biochemistry & Molecular Biology emphasis, measurement with radioactive iodine. He was also a pioneer in the study of hormones involved Roger Mar-Tang (CDB) wins the MCB based on academic achievement in MCB courses and faculty recommendation. A stipend of in lipid metabolism, which influences arte- Departmental Citation $1200 is given to support the student’s under- riosclerosis. Each year, several Chaikoff awards graduate research during the summer between are given in recognition of outstanding The Departmental Citation represents the high- junior and senior years with the MCB faculty achievement and excellence in the Cell & est achievement each year by a graduating senior member of his or her choice. Developmental Biology and Neurobiology in the MCB Department, not only in terms of emphases. Awardees receive a $500 prize. overall grade point average, but in major course- Emily Wood wins the Grace Fimognari work, quality of research, and other such factors Memorial Award Erika Shor wins the Outstanding that indicate promise of great success in the stu- Undergraduate Geneticist Award dent’s career. The Citation is awarded by a vote Established in 1969, this prize is awarded to an of the Undergraduate Affairs Committee outstanding graduating senior in the BMB This prize is given each year to the student who (UAC), after having examined the records of the emphasis of the MCB major, based on the same has most distinguished himself or herself in nominees from each MCB Division. The winner criteria as the Departmental Citation. The genetics research. Award of the prize is based receives $500 and a certificate. awardee receives $500 and a certificate. on the student’s oral presentation of his or her research at the annual Genetics Undergraduate Ryan K. Louie wins the Kazuo Gerald Research Symposium and by his or her honors Yanaba & Ting Jung Memorial Fund Prize thesis. The awardee receives $500 and a certificate. This prize is made possible by the generosity of family, friends, and associates of the late Kazuo Gerald Yanaba and Ting Jung, two graduates of Outstanding Immunologist Award the Microbiology and Immunology major and former employees of Cetus Corporation. Award No selection made this year. of the prize is based on the students’ oral presen- tation of their research at the annual BMB Undergraduate Honors Research Symposium and by their honors theses. The awardee receives $500 and a certificate.

10 FAC ULTY NEWS

PROMOTIONS ADMINISTRATIVE

■ Tom Alber (BMB) promoted to Full Professor, effective 7/1/97. APPOINTMENTS ■ Georjana Barnes (Gen) promoted to Associate Adjunct Professor, effective 7/1/98. ■ Randy Schekman and Jim Allison appointed Department ■ David Drubin (Gen) promoted to Full Professor, effective 7/1/98. Co-Chairs, effective 1/1/98. ■ ■ Gian Garriga (Gen) promoted to Associate Professor, effective 7/1/98. David Raulet appointed Immunology Division Head, effective 8/1/97. ■ Ellen Robey (Imm) promoted to Associate Professor, effective 7/1/98. ■ Hsiao-Ping Moore appointed Graduate Affairs Unit Head, effective 11/1/97. ■ David Drubin appointed Graduate Affairs Unit Head, effective FACULTY AWARDS 7/1/98. AND HONORS RECEIVED SINCE JULY 1, 1997

Biochemistry and Molecular Biology Faculty ■ Hiroshi Nikaido was elected Fellow of the ■ Jasper Rine received an endowed chair as ■ Bruce Ames was given the Robert A. Kehoe American Academy of Microbiology. the Richard and Rhoda E. Goldman Award of Merit for notable contributions to ■ Dan Portnoy gave the Plenary Lecture at the Distinguished Professor of Biology. occupational medicine and was elected as 71st Annual Meeting of the Japanese Society ■ William Skarnes was named a 1998 Searle an Honorary Member of the Japanese for Bacteriology. Scholar. Pharmaceutical Society. ■ Jesse Rabinowitz, professor emeritus, was ■ Richard Calendar was appointed to the elected Fellow of the American Academy of Cell and Developmental Biology Faculty Evaluation Panel for HHMI Predoctoral Microbiology. ■ Zac Cande was appointed Research Fellowships. ■ Randy Schekman is President-elect of the Professor of the Miller Institute for Basic ■ Robert Glaeser was appointed to the U.S. American Society for Cell Biology, and he Research in Science for 1999-2000. National Committee for the International delivered the Sonneborn Annual Lecture at ■ Lester Packer was awarded an honorary Union of Pure and Applied Biophysics for a Indiana University. doctorate degree from the University of 3-year term. ■ Jeremy Thorner was appointed Research Rennes, France. ■ Alex Glazer was the 1997-98 ASM Professor of the Miller Institute for Basic ■ Tito Serafini received a Searle Scholar Foundation for Microbiology Lecturer; Research in Science for 1999-2000, Award, a Beckman Young Investigator gave the Keynote Lecture at the 1997 was elected Vice-Chair for 1998 and Award, and the Mary Elisabeth Rennie International Symposium on Marine Chair for 1999 of the Gordon Research Endowment for Epilepsy Research Grant. Cyanobacteria and Related Organisms, Conference on Second Messengers and Paris, France; and was appointed Director, Protein Phosphorylation, and was elected a Neurobiology Faculty University of California Natural Reserve Member of the 1998-99 Nominating ■ Yang Dan was named a Sloan Fellow and System. Committee of the American Society for received a Beckman Young Investigator ■ Caroline Kane was appointed to the Biochemistry and Molecular Biology. Award. National Institutes of Health Advisory ■ Robert Tijan was elected to the American ■ Corey Goodman won the Gairdner Board for the Office of Research into Academy of Arts and Sciences and was Foundation International Award for Minority Health, effective January 1, 1998. elected Fellow of the American Academy of Achievement in Medical Sciences and the ■ Judith Klinman was elected President of the Microbiology. Ameritec Prize for basic research toward American Society for Biochemistry and a cure for paralysis. Molecular Biology. Genetics Faculty ■ Sydney Kustu received a 10-year MERIT ■ Thomas Cline was appointed to the Immunology Faculty Award from the NIH and a Visiting Executive Council of the American Academy ■ James Allison was selected as Investigator Gauss Professorship at the University of of Arts and Sciences. of the Howard Hughes Medical Institute Goettingen, Germany. ■ Michael Levine was elected to the National effective July, 1997; won a Research Award ■ Susan Marqusee received a Hellman Family Academy of Sciences. from The Association for the Cure of Faculty Fund Award, was named Chair of ■ Barbara Meyer was selected as Investigator Cancer of the Prostate, CapCure the 1999 Proteins Gordon Conference, and of the Howard Hughes Medical Institute Foundation; and was elected Fellow of the was elected to the 1997-99 Nominating effective July, 1997. American Academy of Microbiology. Committee of the Protein Society. 11 1997-98 MCB

PhD GRADUATES ■ Laura Corral (Raulet) Novel Monoclonal ■ Otis Littlefield (Nelson/Thomas Ernest) Antibodies Against Mouse NK Cell Receptors. Crystal Structures of the Kluyveromyces lactis ■ Heat Shock Transcription Factor DNA- ■ Melissa Adams (Rio) Molecular Genetic Gene Cutler (Tjian) A Functional and Binding Domain Complexed with DNA. and Biochemical Characterization of the Structural Characterization of the Drosophila ■ P-element Somatic Inhibitor Protein, Transcription Factor ADF-1. Kevin Mitchell (Goodman) Combinatorial A Drosophila Alternative Splicing Factor. ■ Judith Davie (Kane) Genetic Interactions of Mechanisms Involved in Commissure Formation and Motor Axon Target Selection ■ Michael Albrecht (Meyer) Analysis of Dosage the Transcription Elongation Factor TFIIS in Drosophila. Compensation and Chromosome Segregation from Saccharomyces cerevisiae. ■ in C. elegans. ■ Andrew Dillin (Rine) Studies of the Origin Mario Pantoja (Anderson) Molecular and Biochemical Studies of the Maternal Pathway ■ Jeanne Baker (Raulet) Elements That Recognition Complex in the Yeast Required for Embyronic Dorsoventral Polarity Control the Developmental Pattern of V(D)J Saccharomyces cerevisiae. in Drosophila melanogaster. Recombination and Transcription at the T ■ Jason Dugas (Ngai) Olfactory Receptor ■ Cell Receptor γ Locus. Genes: Genomic Organization and Rhett Pascual (Nandi) The Activation of the H-ras Gene in N-Methyl-N-Nitrosourea- ■ Renee Baran (Garriga) The Role of the Transcriptional Regulation. Induced Rat Mammary Tumors is Regulated unc-42 Gene in Neuronal Differentiation and ■ Eva Finney (Shatz) Role of Subplate Neurons by the Ovarian Hormone Estradiol. Axon Pathfinding in C. elegans. in Cortical Development. ■ Sussan Paydar (Jacobs) Anatomical and ■ Paul Baum (Garriga) Molecular Genetic ■ Kenneth Frauwirth (Shastri) Presentation of Functional Mapping of Primary Sensory Analysis of the Migrations of the Endogenous Antigens by MHC Class II Neurons in the Cricket Cercal System. Caenorhabditis elegans Hermaphrodite Molecules: Analysis of Processing Pathways ■ Specific Neurons. and the Function of the Invariant Chain. Elicia Penuel (Martin) Characterization of Cellular Transformation by v-Src. ■ Eileen Beall (Rio) Regulation of the P- ■ Balasubramanian Girish (Miller, J.) Cricket ■ Element Transposase Protein by the Wind Detection: A Study of the Coding of Carmen Robinett (Dunaway) Identification Drosophila DNA-dependent Protein Kinase. Temporally Varying Vector Stimuli by a and Analysis of an Insulator Element within the Intergenic Spacer of the Xenopus rRNA ■ Pierre Beaurang (Tjian) Reconstitution of Well-Defined Neural Ensemble. Genes. Chromatin Regulated Transcriptional ■ Richard Harris (Isacoff) The Permeation ■ Activation at the HIV LTR. Pathway of a Potassium Channel. Christine Rousseau (King) Genetics of Perinatal HIV-1 Infection. ■ Victor Boyartchuk (Rine) Prenylation- ■ Christian Hofmann (Drubin) Genetic ■ dependent Processing of Proteins in Identification of Cytoskeletal Elements in Nell Shimasaki (Kane) Structure Function Saccharomyces cerevisiae. Saccharomyces cerevisiae. Analysis of the Eukaryotic Transcription Factor TFIIS. ■ Christine Brown (Sachs) Messenger RNA ■ Deborah Isaksen (Weisblat) The Identi- ■ Poly(A) Tail Metabolism in Saccharomyces fication of a TGF-Beta Class Gene and the Cheryl Smith (Martin) Biochemical and cerevisiae: Roles for the Pab1p-dependent Regulation of Endodermal Precursor Cell Genetic Characterization of the cdc18+ Gene Poly(A) Nuclease. Fusion in the Leech. of Schizosaccaromyces pombe. ■ ■ Patricia Buse (Firestone) Regulation of the ■ Daniel Joo (Calendar) Studies of the Susan Uptain (Chamberlin) Structural and Serum- and Glucocorticoid-Inducible Protein Interaction between the Heat Shock σ 32 Functional Characterization of Escherichia coli Kinase by Hormones and the Cell Cycle. Factor and Core RNA Polymerase in RNA Polymerase Ternary Complexes during Transcript Elongation and Termination. ■ Aaron Chamberlain (Marqusee) Partially Escherichia coli. ■ Folded Conformations of E. coli ■ Andrew Kasarskis (Harland) Isolation and Karen Zito (Isacoff) Mechanisms Controlling Ribonuclease H. characterization of ENU-induced Mutations Synapse Formation and Development at the Drosophila Neuromuscular Junction. ■ John Chuang (Schekman) Differential Disrupting Normal Postimplantation Trafficking and Timed Localization of Two Development in the Mouse. Chitin Synthase Proteins, Chs2p and Chs3p, in Saccharomyces cerevisiae.

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