Colloquium der Gesellschaft für Biologische Chemie in Mosbach Baden – serie

The scope of the 20th Mosbach Colloquium may be best illustrated by the following notes sent to the speakers when the colloquium was organized. "1) The application of inhibitors in cell biology has led to decisive insight into the organisation of cellular units. The subject should be treated against a background of current aspects of cell biology. In some areas of research, a fairly complete picture of the functions and cooperative interactions of the units has already emerged. We will discuss mainly these areas. 2) At this colloquium we want to contribute illustrations of the useful application of inhibitors to biological problems. Due to limited knowledge, inhibitors are sometimes incorrectly employed. This applies both to the planning of investigations and to the con· clusions drawn ("use of inhibitors by uninhibited workers"). 3) Inhibitors themselves are interesting substances and their mechanisms of action constitute fascinating problems." The colloquium has been subdivided into five sections. The known chemical structures of the inhibitors discussed are given in an Appendix. We gratefully appreciate the cooperation of the speakers. To a great extent, they managed the coordination of contributions to each of the five subdivisions. We regret that no contributors from Eastern Europe were able to participate.

It is two years since a general meeting of the Gesellschaft fur Biologische Chemie first requested us to organize the 21 st Mosbach Colloquium on mammalian reproduction, and one year since we received final authorization to do so. The present volume contains the papers read at the Colloquium, but the discussions have been omitted because writing and proof­ reading them would have delayed the appearance of this volume for an unjustifiable long time. Besides, in most cases the discussion was of a relatively specific nature and we did not consider it essential, bearing in mind that the purpose of the Mosbach Col­ loquia is to provide advanced further education for the non­ specialist. One of us has referred to this and to the topical structure of the 21 st Colloquium in the introductory and final remarks. Helpful suggestions for organizing the program were made by some of the invited speakers, but the first important impulses VON BERSWORDT-WALLRABE, Dr. ELGER, Dr. came from Dr. GERHARDS, Dr. NEUMANN, and Dr. UFER to whom we here wish express our thanks. Thanks are also due to those whose donations, some of which were very generous, made it financially possible to organize the Colloquium. HEINZ GIBIAN July 1970 ERNST JURGEN PLOTZ Contents Introduction. H. GIBIAN (Berlin) 1 General Outline about Reproductive Physiology and its Developmental Background. A. JOST (Paris) .. 4 The Significance of Hormones in Mammalian Sex Differentia­ tion as Evidenced by Experiments with Synthetic Andro­ gens and Antiandrogens. W. ELGER, F. NEUMANN, H.

HERBERT FISCHER Max-Planck-Institut fur Immunbiologie, Freiburg-Zahringen With 3 Figures Ladies and Gentlemen: On behalf of the organizers of the 22nd Mosbach Colloquium, Msrs. HOLZL-WALLACH, STOFFEL, WIEGANDT and myself, I bid you all a hearty welcome. We thank you all for coming and naturally feel particular appreciation for the presence of the invited speakers. But, thanks to the tradition that the Mosbach Colloquia have enjoyed for 22 years we did not need to work very hard, since most of our invitations were accepted without hesitation. Perhaps some of you will wonder why Mosbach and its tradi­ tion means so much, especially to the older ones amongst us. In any event, at a time when we were much hungrier and thirstier than we are today, Mosbach became a unique place where we could satisfy our spiritual as well as our physical hunger. It was here where we could find the friendly and peaceful atmosphere which helped us to establish contacts with colleagues from foreign coun­ tries and from distant scientific fields, which often led to lasting communication and cooperation. The initiator of these Colloquia, my teacher Kurt Felix, im­ parted to these gatherings a pioneer spirit which is more needed today than in the past, particularly because we are now 500 rather than 50 to 100 participants. Indeed, we as organizers, have had to ask ourselves whether it is still possible to have an exciting lecture series combined with the leisure and opportunity for spontaneous questioning and stimulating individual discussion.

The present volume contains the proceedings of the 23rd Mos- bach Colloquium on "Protein-Protein Interactions". It includes the paper by Prof. S. LIFSON who unfortunately was unable to attend. Discussions were included whenever possible in order to make the complete proceedings accessible to the future reader. The colloquium was generously supported by the firms who are corporate members of the Gesellschaft fur Biologische Chemie. Dr. W. B. GRATZER and Dr. L. JAENICKE, as weIl as some of the invited speakers, were a tremendous help in preparing the program and we wish to thank them for their helpfuI suggestions and advice. Our appreciation extends to Prof. E. AUHAGEN and Prof. H. GIBIAN, and their secretaries, who shared the burden of organizing the colloquium. In addition, we wish to express our gratitude to Springer-Ver- Iag, and especially to Dr. H. MAYER-KAUPP for editoriaI help and for the rapid publication of this volume. We hope that the reader, Iike the audience in the Mosbach market hall, will gain an impression of the present state of protein research and of the way in which intermolecular interactions hold specific implications for the structure and function of proteins.Regensburg and Wurzburg, autumn 1972 R. JAENICKE E. HELMREICH Contents Introduction. R. JAENICKE (Regensburg) 1 Molecular Forees. S. LIFSON (Rehovot) ...3 Structure, Function and Dynamics of a ReguIatory Enzyme: Aspartate Transcarbamylase. H. K. SCHACHMAN (Berkeley) 17 Discussion ...54 ...

This volume represents the proceedings of the 24th Mos­ bach Colloquium on "Regulation of Transcription and Trans­ lation in Eukaryotes" which was held April 26-28, 1973, in Mosbach, Germany, under the auspices of the Gesellschaft fiir Biologische Chemie. To the three of us (H. KERSTEN, P. KARLSON and myself) who were commissioned with the invitation of speakers, it was a difficult decision as to whether we should attempt to cover with some twenty contributions as many aspects of this broad topic as possible, or to sacrifice the intellectually perhaps more pleasing but more specula­ tive concepts and to concentrate on a few aspects of gene expression in reasonable detail. We unanimously decided on the latter course, leaving such important and timely topics as for example, hormone action, cyclic AMP and reverse transcription to the proceedings of other symposia, and con­ centrating on the four questions which are most basic to an understanding of the mechanisms of transcription and trans­ lation and for which fragmentary but nonetheless reliable experimental results have become available within the last few years. These are the structure of chromatin, the syn­ thesis of messenger RNA, the structure of the active ribo­ some, and the role of initiation factors in protein synthesis.

This volume contains the Proceedings of the 25th Mosbach Colloquium, the general theme of which is the Biochemistry of Sensory Functions. It was intended, continuing the silver-tradition of these Colloquia, to provide the uninitiated biochemist with an insight into the current status of a line of research in Molecular Biology which, more than many other fields in Biochemistry, has maintained its contacts with and respect for Physiology. The speakers were asked to attempt to outline their topic sufficiently to define the fundamentals and to build up upon this basis the more sophisticated details of their own studies. It is for the reader to evaluate how well both organizer and participants 1 have attained this end • These Proceedings not only mirror the hubs around which several groups of scientists wheel but may also serve as a source of literature references and for the advanced student as an introduction to this highly up-to-date branch of Biochemistry, although no index is provided as the table of con­ tents is considered sufficient to locate most of the s,

The topic of this Mosbach Colloquium was meant as a question to begin with. When I started to study differentiation and morphogenesis in Volvox I hoped for a straightforward answer along prepared groove- only to find out that also here things follow Murphy's Law: they were much more complicated than expected! Succour had to be sought. Thus, the idea arose to put this question before a board of experts. Experience would have warned any ex-service man never to utter an idea or else you would be made responsible, and it came as it had to come: I was made impressario of this gremium; I had to assemble the experts. These Proceedings contain their expertise. I cannot even say that I biased it by my picking. In the beginning I aimed at setting different accents by inclination and force of habit. Then, by trial and error, by advice and declination, the programme shaped itself. It eventually gained momentum of which also the size of this volume is indicative. In this volume are printed all the papers presented - with two regret­ ted exceptions - but not the sometimes lively discussion, which clari­ fied and pruned here and there. It would just have made the size too unwieldy. Differentiation and morphogenesis start with the expression of genes. The development programme reels off the genome and is regulated by the position of the appropriate genes. Their structure is in the focus of gene biochemistry since the decisive tools have become available.

This volume contains the lectures and discussions of the 34th Mosbach Colloquium, organized by the Gesellschaft fur Biologische Chemie in commemoration of otto Warburg's 100th anniversary. Following warburg's main scientific interests the topics of the contributions were related to the hydrogen-transferring enzymes as well as to the oxygen-reducing and oxygen-activating enzymes. Due to the detailed knowledge on the molecular structure of NAD- and flavin-dependent dehydrogenases, a better understanding of enzyme catalysis and especially enzyme evolu- tion has emerged. In the field of oxidases and oxygenases we begin to understand the complex biochemistry of oxygen and realize that binding, reduction, and activation of this molecule have common underlying prin- ciples. Even new metabolic pathways of oxygenases, such as lipoxygen- ases or cyclooxygenase, have recently been discovered and promise new innovations in cell regulation and medicine. Thanks to the cooperation of all authors, a well-balanced mixture of basic information and progress report was provided.We especially ap- preciate Professor Bucher's charming, thoughtful, and honest contri- bution on Otto Warburg as a skilful scientist and colorful personality. The editors are indebted to the sponsoring organizations, the Deutsche Forschungsgemeinschaft and several industrial companies, and especial- ly acknowledge the competent help of Mrs. H. Allen in the editorial work. H. SUND October 1983 V. ULLRICH Contents Otto Warburg: A Personal Recollection Th. BUcher (With 15 Figures) **. . *****. **********. . ****. . ******** NAD-Dependent Dehydrogenases structure-Function Relationships of NAD-Dependent Dehydrogenases M. G.

The 35th N:osbach Colloquium "The Impact of Gene Transfer Techniques in Eukaryotic CeU Biology" brought together a number of speakers interested in various aspects of cellular and developmental biology and over 600 other scientists, who listened to the lectures and participated in the lively discussions. The questions and experiments described were very varied, but all of them illustrated the importance of recombinant DNA technology. The powerful techniques of identifying and isolating DNA sequences, followed by their introduction into living cells and even into the germ cells of multicellular organisms, have pervaded nearly every branch of molecular biology. The presentations and discussions that followed showed that recombinant DNA has tremendously increased our potential for fundamental research. Now, and for some time to corne, these contri­ butions and the resulting increase in our understanding of life will be the main result of gene manipulation. There will, however, also be applications that will lead to new industrial processes. One section was devoted to novel ways of vaccine production and another to herbicide resistance. These applications are a matter of intense debate in the public domain today. Although they reach beyond the scope of the research labora.tory at a university or research institution, scientists have the knowledge necessary to judge these developments and are sometimes directly involved. There­ fore the development of industrial qene technology requires the attention of the whole scientific community. We hope that this Symposium has also served this purpose.

The field of the neurosciences is one of the most rapidly growing in present biological research. Its molecular aspects are dealt with by the discipline of neurobiochemistry. As the theme of the Mosbacher Colloquium, we chose this term rather than the term "neurochemistry", in order to stress the dynamic biochemical aspects of present molecu- lar neurobiology and to avoid the flavor of being purely descriptive and "static", which is frequently associated with the term neurochem- istry. This appears the more warranted, since the natural products and analytical chemistry phase of discovering the basic chemical com- ponents of the nervous system has passed its culmination. The period of assessment has laid the foundation for studying the dynamic inter- play of the various chemical components in the actual biological opera- tion of nervous tissue. Thus, neurobiochemis~ry is that part of the neurosciences which is dominated by the ways of thinking and the metho- dology of biochemistry. For this Colloquium only topics were selected that deal with the biochemistry of neurons.Thus, we excluded from the agenda other neu- ral cells such as glial cells (astrocytes, ependymal cells, oligoden- drocytes), meningeal cells, and capillary endothelial cells. This restriction was applied for two reasons: (1) The time available for the meeting did not allow an extensive display of the whole spectrum of neurobiochemical research. (2) The biochemistry of neurons is far more advanced than that of any other cell type of the nervous system *.

Elucidation of the mechanisms of pathogenesis underlying the diseases caused by viruses and bacteria has fascinated scientists for many years in two ways. Firstly, these pathogenic agents represent relatively sim­ ple biological systems for the study of basic biological processes such as replication, gene regulation, genetic variability and host-pathogen interactions. Secondly, process in this field is valuable in a practi­ cal sence, since it can help in the control of these diseases. The avail­ ability of new genetic and immunological techniques, especially recom­ binant DNA methods and monoclonal antibody technology, has provided powerful tools for unravelling the genetic, biochemical and immunologi­ cal basis of viral and microbial pathogenesis. Molecular cloning has allowed the isolation of single genes or groups of genes related to phenotypes which appear to be immunologically important for pathogene­ sis. The specific elimination of such genes from the complex genomes of the pathogens can now be achieved with similar genetic techniques. These genetic studies have provided additional information on the role played by specific phenotypic traits in pathogenesis, especially when combined with relevant animal model systems. Furthermore, the struc­ tural analysis of important virulence factors and surface antigens may allow the prediction of antigenic domains suitable for the development of new vaccines. The 38th Mosbacher Colloquium focuses on the molecular basis of viral and microbial pathogenesis. The virology part begins with the well­ studied plant viroids. The unusual structure of their genome, as well as knowledge about their replication and pathogenicity, are presented.

Protein engineering has had considerable impact on basic and applied research in biochemistry and molecular biology. It is already in use as a tool in molecular biology, but it is beginning to strongly influence the planning of experiments in biology everywhere, and, with even fur­ ther-reaching consequences, the appointment politics in research in­ stitutions and industries. Protein engineering, perhaps more than any other methods of protein analysis and peptide synthesis, has shown that proteins are organic molecules governed by the universal laws of chemistry and physics. How­ ever, as was the case with other new powerful methods and techniques, protein engineering tempts to an exploration of its limitations and thus generates more questions than it answers. The 39th Mosbacher Colloquium on Protein Structure and Protein Engi­ neering is not the first conference on this topic and it will not be the last. The important issues are obviously techniques of protein en­ gineering, examples of application, and the basic framework of protein structure and stability within which reasonable experiments can be de­ signed; conversely also, what we can learn about protein structure, dynamics, and folding from such experiments. Experiments in this direc­ tion aim at elucidating the folding code in the long run, but help to exploit the role of individual amino acid residues in catalysis, pro­ tein stability, and binding specificity in selected proteins now.

Recent years have seen tremendous progress in the field of hormone action and consequent signal transduction. The 40th Colloquium Mosbach was devoted to the discussion of results concerning the molecular process of hormone action, especially the processes following hormone binding to the corresponding receptors. Structural and functional aspects of steroid hormone receptors as well as ion-channel-coupled and enzyme-linked receptors were treated in detail. Particular interest focussed on the latest results concerning transcriptional control, protein phosphorylation, the role of G-Proteins, oncogene proteins, involvement of phospholipases and the regulation of ion channels.