Beckman Center Research Articles

The bacterial flagellum: From genetic network to complex architecture

Department of Developmental Biology Beckman Center Stanford University School of Medicine Stanford, California 94305 A rotating propeller at the cell surface, driven by a trans- membrane proton gradient, provides many bacteria with the ability to move and thus respond to environmental sig- nals. To acquire this powerful capability, the bacterial cell is faced with the challenge of building a tiny rotary engine at the base of the propeller. Although the motor is an- chored in the cytoplasmic membrane, a significant portion of the entire mechanism extends into the cytoplasm and, at the other end, out into the environment (Figure 1). At least 20 individual proteins are used as parts for this com- plex structure and another 30 are used for its construction, function, and maintenance (Macnab, 1992). To carry out the feat of coordinating the ordered expres- sion of about 50 genes, delivering the protein products of these genes to the construction site, and moving the cor- rect parts to the upper floors whiie adhering to the design specifications with a high degree of accuracy, the cell re- quires impressive organizational skills. The construction scheme must deal with fundamental questions in struc- tural and developmental biology. How does the cell mea- sure the length of a component made up of polymerized subunits? When the appropriate length is reached, how does the cell turn off the assembly of one part of the struc- ture and switch on the assembly of the next part? Are there checkpoint mechanisms that determine whether one flagellum component has been completed and that it is okay to start construction of the next component? How is this information conveyed to the expression of the flagellar genes? Because the assembly of the flagellum proceeds in large measure by the passage of structural proteins through a central channel to its distal tip (lino, 1969; Emer- son et al., 1970), what is the export mechanism and how does it choose the proteins that are allowed entry into the pipeline? This minireview addresses some of the mecha- nisms used by the cell to solve these problems in subcellu- lar morphogenesis, many of which provide unique insight into the versatility and ingenuity of the bacterial cell, and some of which provide new paradigms for cellular morpho- genesis. Both the design of the flagellum and some of the newly discovered regulatory tricks used to organize its construc- tion have been conserved among diverse and evolution- arily distant bacteria. What's more, some of the regulatory mechanisms used for flagellar construction appear also to be used for phage assembly and, surprisingly, for the selective transport of virulence factors from the bacterial cell to their animal or plant hosts (Russel, 1994; Rosqvist et al., 1994).

Including Chemistry In Science History

Over the past 50 years, the history of science has become firmly established as an academic discipline. Many universities and colleges have one or more faculty members specializing in this field. As the book reviews in Isis , the principal journal in the U.S. for articles on science history, indicate, many monographs are published every year, in both the U.S. and abroad, on topics relating to the history of science. Chemistry has shared in this increased activity. Membership in the American Chemical Society's Division of the History of Chemistry has risen markedly in recent years, to about 700 members today, and the division publishes its own journal. The Chemical Heritage Foundation, which includes the Beckman Center for the History of has become a nucleus for promoting the study of chemical history. Despite all this progress, however, Aaron J. Hide's classic volume, Development of Modern Chemistry, published in 1964, has not been superseded. Nor has the ...

A temporally controlled sigma-factor is required for polar morphogenesis and normal cell division in Caulobacter.

The transcription of many spatially and temporally controlled flagellar structural genes in Caulobacter requires the RNA polymerase sigma 54 subunit. Like flagellar biogenesis, stalk formation is an asymmetric polar morphogenesis that occurs once each cell cycle in response to internal cell cycle signals. We have isolated the sigma 54 gene (rpoN) and describe here a novel role for this alternative sigma-factor in cell differentiation: It is required for the biogenesis of both polar structures, and the disruption of the rpoN gene results in aberrant cell division. Surprisingly, the transcription of rpoN is temporally regulated during the cell cycle; it increases 10-fold commensurate with stalk formation and just before the onset of flagellar gene expression. These results suggest that sigma 54 abundance responds to cell cycle cues and is involved in the global timing of the central events of Caulobacter development, whereas the transcriptional activators of sigma 54-dependent promoters are responsible for the refined control of the expression of individual or small groups of genes required for each specific event.

Basic research: the lifeline of medicine

The FASEB JournalVolume 6, Issue 13 p. 3143-3145 Highlights Basic research: the lifeline of medicine Arthur Kornberg, Arthur Kornberg Department of Biochemistry, Stanford University School of Medicine, Beckman Center, Stanford, California, 94305-5307 USAEditor's note: This address was given by Dr. Kornberg at a national symposium on “Today's Opportunities, Tomorrow's Health: The Future of Biomedical Research in America” held in San Antonio, Texas, February 2–4, 1992, to mark the 50th anniversary of the Southwest Foundation for Biomedical Research, and co-sponsored by the U.S. Department of Health and Human Services and the National Institutes of Health. Dr. Kornberg's talk followed one by NIH Director Bernadine Healy in which she presented NIH's targeting of specific health (disease) goals. Dr. Kornberg's address is reproduced from the symposium report by permission of the copyright holder. Elements of the address are reprinted with permission from Clinical Chemistry, (1991), Vol 37, No 11, pages 1895–1899, entitled: “Understanding Life as Chemistry.” Copyright American Association for Clinical Chemistry, Inc.Search for more papers by this author Arthur Kornberg, Arthur Kornberg Department of Biochemistry, Stanford University School of Medicine, Beckman Center, Stanford, California, 94305-5307 USAEditor's note: This address was given by Dr. Kornberg at a national symposium on “Today's Opportunities, Tomorrow's Health: The Future of Biomedical Research in America” held in San Antonio, Texas, February 2–4, 1992, to mark the 50th anniversary of the Southwest Foundation for Biomedical Research, and co-sponsored by the U.S. Department of Health and Human Services and the National Institutes of Health. Dr. Kornberg's talk followed one by NIH Director Bernadine Healy in which she presented NIH's targeting of specific health (disease) goals. Dr. Kornberg's address is reproduced from the symposium report by permission of the copyright holder. Elements of the address are reprinted with permission from Clinical Chemistry, (1991), Vol 37, No 11, pages 1895–1899, entitled: “Understanding Life as Chemistry.” Copyright American Association for Clinical Chemistry, Inc.Search for more papers by this author First published: 01 October 1992 https://doi.org/10.1096/fasebj.6.13.1397835Citations: 4 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume6, Issue13October 1992Pages 3143-3145 RelatedInformation

Professor Al Nier and his influence on mass spectrometry

Professor Alfred Otto Carl Nier has had a singular influence on the art and science of mass spectrometry over the last 55 years. I had the pleasure of conducting an oral history interview of Dr. Nier in the spring of 1989 at his office and laboratory at the University of Minnesota. I was assisted in this endeavor by Thomas Krick of the Biochemistry Department staff. The interview was underwritten by the American Society for Mass Spectrometry. The following highlights are excerpted from 10 1/2 hours of material recorded during the interview. The complete set of tapes, a full transcript, pictures, and other material collected during the interview are archived with the Beckman Center for the History of Chemistry in Philadelphia.

Conference Report

Although historians have much to contribute to understanding such "Big Science" projects as the Human Genome project, they also face special challenges in placing these ongoing events in historical context. To address these problems from an interdisciplinary perspective, the Beckman Center for the History of Chemistry brought together a group of scholars and students of contemporary science on September 12-13, 1991, with a specific mandate to explore their common methodologies. Sponsored by the Andrew W. Mellon Foundation, the conference on Writing History of Science While it Happens revealed that the difficulties faced by historians interested in contemporary science are shared by scholars of other disciplines. Historians, journalists, sociologists, and anthropologists increasingly share both tools and subjects of interest.

Changes in Presynaptic Function during Long‐Term Potentiation

Annals of the New York Academy of SciencesVolume 635, Issue 1 p. 208-220 Changes in Presynaptic Function during Long-Term Potentiation RICHARD W. TSIEN, RICHARD W. TSIEN Department of Molecular and Cellular Physiology, Beckman Center, Stanford University Medical Center, Stanford, California 94305Search for more papers by this authorROBERTO MALINOW, ROBERTO MALINOW Department of Molecular and Cellular Physiology, Beckman Center, Stanford University Medical Center, Stanford, California 94305 Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242.Search for more papers by this author RICHARD W. TSIEN, RICHARD W. TSIEN Department of Molecular and Cellular Physiology, Beckman Center, Stanford University Medical Center, Stanford, California 94305Search for more papers by this authorROBERTO MALINOW, ROBERTO MALINOW Department of Molecular and Cellular Physiology, Beckman Center, Stanford University Medical Center, Stanford, California 94305 Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242.Search for more papers by this author First published: October 1991 https://doi.org/10.1111/j.1749-6632.1991.tb36493.xCitations: 14 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume635, Issue1Calcium Entry and Action at the Presynaptic Nerve TerminalOctober 1991Pages 208-220 RelatedInformation

New directions in the history of the chemical sciences and technologies

A conference sponsored by the Beckman Center called Chemical Sciences in the Modern World provided a unique forum to generate new perspectives on the last 150 years of chemical history. This paper provides readers with highlights of the conference that could enhance chemistry teaching and encourage public understanding.

Conference Offers Insights on Challenges Facing Science Historians

New insights on challenges facing science historians and on ways to enhance public understanding of science were aired recently at Chemical Sciences in Modern World a wide-ranging conference on history of chemistry. Sponsored by Beckman Center for History of Chemistry, and held in Philadelphia, meeting was organized by Seymour H. Mauskopf, professor of history at Duke University, and Robert Kohler of department of history and sociology of science at University of Pennsylvania. A unique aspect of conference was presence of three disparate groups among attendees: historians, chemists, and high school chemistry teachers. This diversity resulted in questions being raised on how to narrow gap between science historians on one hand and chemists and chemical educators on other, and on ways to make chemical history more relevant to its intended audience. At meeting, says Mauskopf, the historians raised issues ...

Chemistry and Cannon: J.-L. Proust and Gunpowder Analysis

Chemistry and Cannon: J.-L. Proust and Gunpowder Analysis SEYMOUR H. MAUSKOPF D’un instrument de guerre à un instrument de labo­ ratoire, les affinités ne changent certainement pas. [J.-L. Proust, “Cinquième mémoire sur la poudre à canon,” Journal de physique, de chimie et d’histoire na­ turelle 73 (novembre 1811): 390] This is the story of an attempt by a major chemist of the late 18th century to develop “useful knowledge” for industry under govern­ ment patronage. The chemist was Joseph-Louis Proust (1754—1826; known as Luis José Proust in Spain); the industry was munitions; the government was Spanish. It is not a success story in any simple sense; Proust’s research did not bring about any change in the manufacture of gunpowder (although Proust rather passionately argued for some reforms based on his experiments) and his work on gunpowder has been all but forgotten. Yet, on closer scrutiny of Proust’s career, I came to realize the significance of the gunpowder research for it. Although Proust is best known for his work in analytical chemistry (the enunciation of the law of definite proportions, a basic principle of chemical stoichiometry), he carried out research and taught on a wide range of chemical topics, many of them practical. Indeed, it was primarily through his practical chemistry that Proust was enabled to spend his mature and most creative years in Spain in the employ of the Spanish government. Of central importance were his activities as researcher, consultant, and teacher concerning munitions, carried on when he was professor of chemistry at the Royal Artillery School in Segovia (1785—98). Proust Dr. Mauskopf is professor of history at Duke University and, in 1988—89, was Edelstein International Fellow in the History of Chemical Sciences and Technologies at the Beckman Center for the History of Chemistry and the Edelstein Center, Hebrew University of Jerusalem. He is currently researching scientific involvement in explo­ sives and munitions from the late 18th century through World War I. He thanks the secretarial staffs of the Duke Department of History and of the Beckman Center for their expert services; and Alex Roland, Joe Burchfield, and the Beckman Center “brown bag seminar” for their helpful, frank readings of various drafts of the article.© 1990 by the Society for the History of Technology. All rights reserved. 0040-165X/90/3103-0003$01.00 398 Chemistry and Cannon: J -L. Proust and Gunpowder Analysis 399 certainly did not regard his practical chemistry as any less important than his “pure” chemical analysis; as we shall see, he placed high value on his gunpowder research. In fact, this research was probably the most comprehensive and systematic study of gunpowder chemistry of its day. Moreover, it was part of a scientific research tradition devoted to the elucidation of the physics and chemistry of gunpowder that spanned the 18th century.1 Therefore, one of the objectives of this study is to present and analyze Proust’s scientific research on gunpowder for its intrinsic scientific interest and significance. That this work has been neglected is only partly due to its limited application to the munitions industry in its own day; it is also a part of the general neglect that the history of modern scientific investigations of munitions has suffered. The classical study by J. R. Partington has for its focus the medieval and early modern eras and is very sketchy about the history of gunpowder after 1700.2 To discover information about the later period, one is forced to turn to state-of-the-art treatises of the 19th century, with their inevitable “textbook” orientation to the history of science.3 This study and its companion in Osiris are intended to provide partial redress for the shortcomings in the history of the scientific study of munitions. There is also a second objective related to the state patronage of Proust as practical chemist: the examination of Proust’s gunpowder research as a species of the “useful knowledge” so prized by 18thcentury reformers, bureaucrats, and entrepreneurs. There has devel­ oped a vast literature on the issue of the relationship between science and industry encapsulated by this phrase. Much of it has focused on 'Seymour H...

Using Normal Gene as Template May Offer Means of 'In-Place' Genetic Repair

REPAIRING GENES by taking advantage of chromosomal recombination is emerging as a promising new approach to gene therapy, according to speakers at the recent 16th International Congress of Genetics in Toronto. Although gene therapy was once thought to be nearing clinical trials, numerous technical problems have kept it in the laboratory. One principal stumbling block has been an inability to get inserted genes to express proteins at useful levels in animal models. The difficulty, many investigators say, arises from the vehicles used to transport genes into the cell. The most widely used vehicles, modified retroviruses, are essentially unguided missiles that deposit their cargo randomly about the genome. The transported genes, out of their customary positions, are usually only temporarily activated, if at all. One solution may be to repair the defective gene in place, suggests Paul Berg, PhD, director of the Beckman Center for Molecular and Genetic Medicine, Stanford (Calif)