Special
Feature
Biophysics
of the nineties:
MAURIZIO
BRUNORI*2
AND
#{176}Departmentof Biochemical Biology,
The Weizmann
HENRYK
Sciences,
Institute
on the road to Budapest EISENBERG1
University
of Science,
1
of Roma
Rehovot,
The successful planning of scientific congresses requires intensive preparation and close interaction between scientists familiar with and highly competent in a variety of fields represented in a given congress. Science is moving at a fast pace in our days and, in addition to being a record of past and present accomplishments, one would like to ascertain the directions in which a given scientific activity will move in the future. Uncertainties in precisely defining the boundaries and aims of biophysics as a modern branch of science have previously been discussed (1, 2) and have led to interesting comments (3). We were fortunate that our recent discussions with other fellows of the International Union for Pure and Applied Biophysics (IUPAB) Council, centering around the XI International Congress of Biophysics1, were held in Rome on the grounds of the Accademia Nazionale dei Lincei, of which Galileo Galilei was a member from 1611. Galileo’s fame and personal misfortunes rest strongly on the principle that precise observations and logical conclusions are essential in understanding the correct laws of Nature (see Fig. 1), rather than using a classic dogmatic approach favored by the Establishment. Very much later, while climbing up the steep Gianicolo Hill on a clear February night during the council meeting in Rome this year, we were told of a statement made by Stanislav Ulam, when asked for his opinion about biology and physics: “Ask not what physics can do for biology, but rather what biology can do for physics.” Let us therefore not indulge in narrowness of one kind or the other but following in the steps of our illustrious predecessors rather spread our interest over a broad range of sources of human creative endeavor. We have, until recently, only been able intuitively to guess how the world we inhabit evolved from an inanimate glowing chaotic object, lacking an oxidizing atmosphere, to its present hosting of turbulent “intelligent” living creatures. By the combined use of physical, chemical, mathematical, and biological thought, it has now become possible to attempt an understanding of how biological macromolecules, the basic building blocks of what is called life, evolved from inanimate to self-reproductive and self-concious entities. Proteins and nucleic acids are highly complex and dynamic structures, mutually interacting in processes relating to the maintenance and propagation of life. It has now become possible to relate structure to function, and to describe complex mutual interactions, by combined use of powerful experimental approaches, such as X-rays, neutrons and laserlight scattering, multidimensional NMR, time-resolved spectroscopy, and molecular dynamics simulations. The time scale of X-ray crystallography has been reduced considerably, and the possibility of obtaining structural dynamics of proteins and nucleic acids at high resolution is now possible. Here a fundamental question is (today like yesterday) related to the basic rules governing protein folding in the test tube and in vivo; in spite of significant progress in recent times, a set of reliable rules to compute the 3D structure of a protein from its sequence is not yet available. This issue has aquired even greater significance in the perspective of the
‘La Sapienza
Rome,
Italy;
tDepartment
of Structural
Israel.
‘
.,-
Figure 1. Title page of Galileo’s pamphlet on the solar spots, 1623 (by permission of the Accademia Nazionale dci Lincei, Rome).
‘The 11th International Biophysics Congress will take place in Budapest, Hungary, July 25-30, 1993. Inquiries for registration, submission of abstracts, etc., should be sent to Dr. G. Garab, Secretary General ICB ‘93, Hungarian Academy of Sciences, Szeged, P.O. Box 521, H-6701, Hungary. FAX: 36-62-53656, 23600, 13726. The abstract deadline is March 31, 1993. The same deadline applies to the registration fee (DEM 500, students DEM 250), which will be increased by 50 and 25 DEM, respectively, for late registration. Financial assistance is available for young scientists and will cover “a substantial part of the travel and accommodation expenses” The registration fee will be waived. Awards will be limited to young scientists who do not yet have a permanent salaried position. Apply by November 30, 1993, to Professor J. Tigyi, Institute of Biophysics, Medical University, H-7643 Pecs, Hungary; FAX: 36- 72-14017. 2To whom correspondence should be addressed, at: Dipartimento di Scienze Biochimiche, Universita’ di Roma ‘La Sapienza’, Piazzale A. Moro 5, 00185 Rome, Italy.
-JflAiC VnI fl,tnhpr qcfl w.fasebj.org by Iowa State University Serials Acquisitions Dept (129.186.138.35) on January 13, 2019. The FASEB Journal Vol. ${article.issue.getVolume()}, No. ${article.issue.getIssueNum
massive sequence information that HUGO will soon bring into the open, and which may acquire greater value once we are able to predict from primary structure how proteins fold. Extremely large complex structures composed of proteins and nucleic acids such as the ribosome (the basic protein factory of the living cell) are now analyzed by methodologies eventually leading to atomic resolution. More structural motifs for the recognition of regulatory proteins interacting with specific DNA sequences for control of gene expression are made available by crystallography and NMR. Here the role of supramolecular structure of DNA in the regulation of gene expression is providing challenging results, with findings on the effects of bending, twisting, linking, and so on induced by specific and extensive molecular interactions in the cell nucleus. DNA can be imaged by powerful optical, electron, atomic force and tunneling microscopies as individual molecules or supramolecular assemblies in the living cell. New frontiers in the study of living cells may be reached in the near future by X-ray microscopy, now in the realm of the possible due to new ultrabright Synchrotron sources. From single molecules, or well-defined molecular complexes, on to “crowded” cellular structures, one is able to analyze molecular properties of channels, essential for the transport of vital materials and different signals across biological membranes. Cloning and mutating ionic channels to assess the structural basis of, for example, voltage sensing and ion selectivity, has been very exciting; besides presentations at the congress, a satellite conference (to be held in Konstanz to honor the memory of the late council member Peter L#{227}uger) will cover these subjects in depth. At the other extreme in complexity, recent work on neural networks and integrated functions, to provide models for information processing and rules for self-learning, is of major interest. Here as elsewhere, the challenge is to bridge the gap between the parts and the whole, i.e., between the description of the macromolecules involved in cellular signaling and transduction and the integrated functions of the brain; this is surely a major task presented to modern biophysics in this decade. Molecular biophysics is providing a grasp of contractility, motion, and cellular adhesion in a variety of organisms, of the role of calcium mobility in excitable membranes, of transmembrane signaling, transduction and pumping, of the mechanism of sensory perceptions, of lipid membrane dynamics, and of adaptation to extreme and sometimes harsh environments. The theory of long-range electron transfer is being tested by close comparison of structural and dynamic information in attempts to describe the rules of energy transduction and flow and possibly pave the way to bioelectronics. Many important insights, however, remain to be gained by an approach not restricted to the narrow path of single classical disciplines in order to achieve broader understanding of and successful fight against disease. Studies of tissues, organs, and the whole body have led to major progress by the application of NMR spectroscopy and imaging, which has opened new vistas on the distribution of organic phosphates and other molecules in vivo, in the healthy individual and in disease. Along the same track, oxygen delivery in tissues is being assessed using the “time of flight of photons’ a novel optical method that promises to be of great value to biology and medicine. The impressive achievements of biomolecular sciences stem from the description of the structure of the molecules of life, and their diversified functions, under physiological and pathological conditions. New exciting progress along these lines is seen almost every day. However, a major problem, and perhaps the greatest challenge of this decade,
Albert
Szent-Gyorgyi
is in bridging the gap between extensive quantitative information on the purified cellular components and the behavior of the whole cell or more complex integrated functions, up to brain information processing. Here the danger is to lose vision of the larger horizon intrinsic to global properties, with the extreme specialization unavoidable to understand the complexity of the components. Thus a common thread through biophysics, and a historical challenge to us all, is perhaps the attempt to discover the rules of living organisms with a broad approach and an open mind, deriving inspiration from past experiences. Visiting an exhibition on “La Culture de l’Europe dans le XVII Siecle” at the Accademia Nazionale dci Lincei in Rome, we saw on show Galileo’s telescope and microscope, the instruments of his time used to investigate the laws of nature in the domains of the very large and the very small; although the latter was hardly more than a magnifying lens, we were reminded of his conception to investigate nature at work on the microscopic and the macroscopic scales, keeping in mind the unity of modern science, in line with the lesson of classical Greek philosophers. IUPAB’s decision to place the XI International Biophysics Congress in Budapest focuses on the impact this small nation (just over 10 million people live in Hungary today) has had on civilization and culture. In music, in literature, in the arts, in sports, and in the sciences, the contribution of Hungary exceeds that of several great and powerful nations. Close to our own endeavors let us pay tribute to a few central figures such as Albert Szent-Gyorgyi, Leo Szilard, George Charles de Hevesy, Edward Teller, Janos von Neumann, who have changed the course of modern science. It has happened before in other places, yet the recent choice of a scientist, Bruno F. Straub, to preside over the country emphasizes the positive role of science in Hungary today. We are grateful to Hans Frauenfelder S. Ulam quotation.
(Urbana,
III., USA) for the
REFERENCES H. (1987) Par ma foi! II y a plus de quarante ans que je fais de la biophysique sans que j’en susse rien. Tmzds Biochem. Sd. 12, 283 2. Weber, G. (1990) Whither Biophysics? Annu. Rev. Biophys. Biophys. Chem 19, 1 3. Welch, G. R. (1988) Biophysics: whence it came, where it’s going. Trends Biochein. Sci, 13, 47 1. Eisenberg
#{176}Photo used
with permission
of Academic
Press.
3137 1992 w.fasebj.org byVol. Iowa6StateOctober University Serials Acquisitions Dept (129.186.138.35) on JanuaryNEWS 13, 2019. The FASEB Journal Vol. ${article.issue.getVolume()}, No. ${article.issue.getIssueNum
Feature
Biophysics
of the nineties:
MAURIZIO
BRUNORI*2
AND
#{176}Departmentof Biochemical Biology,
The Weizmann
HENRYK
Sciences,
Institute
on the road to Budapest EISENBERG1
University
of Science,
1
of Roma
Rehovot,
The successful planning of scientific congresses requires intensive preparation and close interaction between scientists familiar with and highly competent in a variety of fields represented in a given congress. Science is moving at a fast pace in our days and, in addition to being a record of past and present accomplishments, one would like to ascertain the directions in which a given scientific activity will move in the future. Uncertainties in precisely defining the boundaries and aims of biophysics as a modern branch of science have previously been discussed (1, 2) and have led to interesting comments (3). We were fortunate that our recent discussions with other fellows of the International Union for Pure and Applied Biophysics (IUPAB) Council, centering around the XI International Congress of Biophysics1, were held in Rome on the grounds of the Accademia Nazionale dei Lincei, of which Galileo Galilei was a member from 1611. Galileo’s fame and personal misfortunes rest strongly on the principle that precise observations and logical conclusions are essential in understanding the correct laws of Nature (see Fig. 1), rather than using a classic dogmatic approach favored by the Establishment. Very much later, while climbing up the steep Gianicolo Hill on a clear February night during the council meeting in Rome this year, we were told of a statement made by Stanislav Ulam, when asked for his opinion about biology and physics: “Ask not what physics can do for biology, but rather what biology can do for physics.” Let us therefore not indulge in narrowness of one kind or the other but following in the steps of our illustrious predecessors rather spread our interest over a broad range of sources of human creative endeavor. We have, until recently, only been able intuitively to guess how the world we inhabit evolved from an inanimate glowing chaotic object, lacking an oxidizing atmosphere, to its present hosting of turbulent “intelligent” living creatures. By the combined use of physical, chemical, mathematical, and biological thought, it has now become possible to attempt an understanding of how biological macromolecules, the basic building blocks of what is called life, evolved from inanimate to self-reproductive and self-concious entities. Proteins and nucleic acids are highly complex and dynamic structures, mutually interacting in processes relating to the maintenance and propagation of life. It has now become possible to relate structure to function, and to describe complex mutual interactions, by combined use of powerful experimental approaches, such as X-rays, neutrons and laserlight scattering, multidimensional NMR, time-resolved spectroscopy, and molecular dynamics simulations. The time scale of X-ray crystallography has been reduced considerably, and the possibility of obtaining structural dynamics of proteins and nucleic acids at high resolution is now possible. Here a fundamental question is (today like yesterday) related to the basic rules governing protein folding in the test tube and in vivo; in spite of significant progress in recent times, a set of reliable rules to compute the 3D structure of a protein from its sequence is not yet available. This issue has aquired even greater significance in the perspective of the
‘La Sapienza
Rome,
Italy;
tDepartment
of Structural
Israel.
‘
.,-
Figure 1. Title page of Galileo’s pamphlet on the solar spots, 1623 (by permission of the Accademia Nazionale dci Lincei, Rome).
‘The 11th International Biophysics Congress will take place in Budapest, Hungary, July 25-30, 1993. Inquiries for registration, submission of abstracts, etc., should be sent to Dr. G. Garab, Secretary General ICB ‘93, Hungarian Academy of Sciences, Szeged, P.O. Box 521, H-6701, Hungary. FAX: 36-62-53656, 23600, 13726. The abstract deadline is March 31, 1993. The same deadline applies to the registration fee (DEM 500, students DEM 250), which will be increased by 50 and 25 DEM, respectively, for late registration. Financial assistance is available for young scientists and will cover “a substantial part of the travel and accommodation expenses” The registration fee will be waived. Awards will be limited to young scientists who do not yet have a permanent salaried position. Apply by November 30, 1993, to Professor J. Tigyi, Institute of Biophysics, Medical University, H-7643 Pecs, Hungary; FAX: 36- 72-14017. 2To whom correspondence should be addressed, at: Dipartimento di Scienze Biochimiche, Universita’ di Roma ‘La Sapienza’, Piazzale A. Moro 5, 00185 Rome, Italy.
-JflAiC VnI fl,tnhpr qcfl w.fasebj.org by Iowa State University Serials Acquisitions Dept (129.186.138.35) on January 13, 2019. The FASEB Journal Vol. ${article.issue.getVolume()}, No. ${article.issue.getIssueNum
massive sequence information that HUGO will soon bring into the open, and which may acquire greater value once we are able to predict from primary structure how proteins fold. Extremely large complex structures composed of proteins and nucleic acids such as the ribosome (the basic protein factory of the living cell) are now analyzed by methodologies eventually leading to atomic resolution. More structural motifs for the recognition of regulatory proteins interacting with specific DNA sequences for control of gene expression are made available by crystallography and NMR. Here the role of supramolecular structure of DNA in the regulation of gene expression is providing challenging results, with findings on the effects of bending, twisting, linking, and so on induced by specific and extensive molecular interactions in the cell nucleus. DNA can be imaged by powerful optical, electron, atomic force and tunneling microscopies as individual molecules or supramolecular assemblies in the living cell. New frontiers in the study of living cells may be reached in the near future by X-ray microscopy, now in the realm of the possible due to new ultrabright Synchrotron sources. From single molecules, or well-defined molecular complexes, on to “crowded” cellular structures, one is able to analyze molecular properties of channels, essential for the transport of vital materials and different signals across biological membranes. Cloning and mutating ionic channels to assess the structural basis of, for example, voltage sensing and ion selectivity, has been very exciting; besides presentations at the congress, a satellite conference (to be held in Konstanz to honor the memory of the late council member Peter L#{227}uger) will cover these subjects in depth. At the other extreme in complexity, recent work on neural networks and integrated functions, to provide models for information processing and rules for self-learning, is of major interest. Here as elsewhere, the challenge is to bridge the gap between the parts and the whole, i.e., between the description of the macromolecules involved in cellular signaling and transduction and the integrated functions of the brain; this is surely a major task presented to modern biophysics in this decade. Molecular biophysics is providing a grasp of contractility, motion, and cellular adhesion in a variety of organisms, of the role of calcium mobility in excitable membranes, of transmembrane signaling, transduction and pumping, of the mechanism of sensory perceptions, of lipid membrane dynamics, and of adaptation to extreme and sometimes harsh environments. The theory of long-range electron transfer is being tested by close comparison of structural and dynamic information in attempts to describe the rules of energy transduction and flow and possibly pave the way to bioelectronics. Many important insights, however, remain to be gained by an approach not restricted to the narrow path of single classical disciplines in order to achieve broader understanding of and successful fight against disease. Studies of tissues, organs, and the whole body have led to major progress by the application of NMR spectroscopy and imaging, which has opened new vistas on the distribution of organic phosphates and other molecules in vivo, in the healthy individual and in disease. Along the same track, oxygen delivery in tissues is being assessed using the “time of flight of photons’ a novel optical method that promises to be of great value to biology and medicine. The impressive achievements of biomolecular sciences stem from the description of the structure of the molecules of life, and their diversified functions, under physiological and pathological conditions. New exciting progress along these lines is seen almost every day. However, a major problem, and perhaps the greatest challenge of this decade,
Albert
Szent-Gyorgyi
is in bridging the gap between extensive quantitative information on the purified cellular components and the behavior of the whole cell or more complex integrated functions, up to brain information processing. Here the danger is to lose vision of the larger horizon intrinsic to global properties, with the extreme specialization unavoidable to understand the complexity of the components. Thus a common thread through biophysics, and a historical challenge to us all, is perhaps the attempt to discover the rules of living organisms with a broad approach and an open mind, deriving inspiration from past experiences. Visiting an exhibition on “La Culture de l’Europe dans le XVII Siecle” at the Accademia Nazionale dci Lincei in Rome, we saw on show Galileo’s telescope and microscope, the instruments of his time used to investigate the laws of nature in the domains of the very large and the very small; although the latter was hardly more than a magnifying lens, we were reminded of his conception to investigate nature at work on the microscopic and the macroscopic scales, keeping in mind the unity of modern science, in line with the lesson of classical Greek philosophers. IUPAB’s decision to place the XI International Biophysics Congress in Budapest focuses on the impact this small nation (just over 10 million people live in Hungary today) has had on civilization and culture. In music, in literature, in the arts, in sports, and in the sciences, the contribution of Hungary exceeds that of several great and powerful nations. Close to our own endeavors let us pay tribute to a few central figures such as Albert Szent-Gyorgyi, Leo Szilard, George Charles de Hevesy, Edward Teller, Janos von Neumann, who have changed the course of modern science. It has happened before in other places, yet the recent choice of a scientist, Bruno F. Straub, to preside over the country emphasizes the positive role of science in Hungary today. We are grateful to Hans Frauenfelder S. Ulam quotation.
(Urbana,
III., USA) for the
REFERENCES H. (1987) Par ma foi! II y a plus de quarante ans que je fais de la biophysique sans que j’en susse rien. Tmzds Biochem. Sd. 12, 283 2. Weber, G. (1990) Whither Biophysics? Annu. Rev. Biophys. Biophys. Chem 19, 1 3. Welch, G. R. (1988) Biophysics: whence it came, where it’s going. Trends Biochein. Sci, 13, 47 1. Eisenberg
#{176}Photo used
with permission
of Academic
Press.
3137 1992 w.fasebj.org byVol. Iowa6StateOctober University Serials Acquisitions Dept (129.186.138.35) on JanuaryNEWS 13, 2019. The FASEB Journal Vol. ${article.issue.getVolume()}, No. ${article.issue.getIssueNum
