Successes in medical biophysics (on the 40th anniversary of the Medico-biological faculty of the Russian State Medical University)

On the occasion of the 40-year anniversary of the Medicobiological Faculty of the Russian State Medical University, the research activity of the biophysics department was summed up. The main result is the creation of medical biophysics as part of the medicobiological science. Scientific investigations of the biophysics department are reviewed. They are presented as follows: chemiluminescence of biological systems; effect of visible light on human and animal molecules and cells; application of luminescence methods in laboratory and clinical investigations; free radicals and their role in cell biology and pathology; medical aspects of molecular biophysics; and biological membranes and cell pathology.     

Life sciences require the third dimension

Novel technologies are required for three-dimensional cell biology and biophysics. By three-dimensional we refer to experimental conditions that essentially try to avoid hard and flat surfaces and favour unconstrained sample dynamics. We believe that light-sheet-based microscopes are particularly well suited to studies of sensitive three-dimensional biological systems. The application of such instruments can be illustrated with examples from the biophysics of microtubule dynamics and three-dimensional cell cultures. Our experience leads us to suggest that three-dimensional approaches reveal new aspects of a system and enable experiments to be performed in a more physiological and hence clinically more relevant context.     

Evolutionary Aspects of Enzyme Dynamics

The role of evolutionary pressure on the chemical step catalyzed by enzymes is somewhat enigmatic, in part because chemistry is not rate-limiting for many optimized systems. Herein, we present studies that examine various aspects of the evolutionary relationship between protein dynamics and the chemical step in two paradigmatic enzyme families, dihydrofolate reductases and alcohol dehydrogenases. Molecular details of both convergent and divergent evolution are beginning to emerge. The findings suggest that protein dynamics across an entire enzyme can play a role in adaptation to differing physiological conditions. The growing tool kit of kinetics, kinetic isotope effects, molecular biology, biophysics, and bioinformatics provides means to link evolutionary changes in structure-dynamics function to the vibrational and conformational states of each protein.     

Fluorescence microscopy today

Fluorescence microscopy has undergone a renaissance in the last decade. The introduction of green fluorescent protein (GFP) and two-photon microscopy has allowed systematic imaging studies of protein localization in living cells and of the structure and function of living tissues. The impact of these and other new imaging methods in biophysics, neuroscience, and developmental and cell biology has been remarkable. Further advances in fluorophore design, molecular biological tools and nonlinear and hyper-resolution microscopies are poised to profoundly transform many fields of biological research.     

Microdosimetry: Principles and applications

Aim

to present the most important aspects of Microdosimetry, a research field in radiation biophysics.

Background

microdosimetry is the branch of radiation biophysics that systematically studies the spatial, temporal and spectral aspects of the stochastic nature of the energy deposition processes in microscopic structures.

Materials and Methods

we briefly review its history, the people, the formalism and the theories and devices that allowed researchers to begin to understand the true nature of radiation action on living matter.

Results and Conclusions

we outline some of its applications, especially to Boron Neutron Capture Therapy, attempting to explain the biological effectiveness of the boron thermal neutron capture reaction.     

Single molecule techniques in DNA repair: A primer

A powerful new approach has become much more widespread and offers insights into aspects of DNA repair unattainable with billions of molecules. Single molecule techniques can be used to image, manipulate or characterize the action of a single repair protein on a single strand of DNA. This allows search mechanisms to be probed, and the effects of force to be understood. These physical aspects can dominate a biochemical reaction, where at the ensemble level their nuances are obscured. In this paper we discuss some of the many technical advances that permit study at the single molecule level. We focus on DNA repair to which these techniques are actively being applied. DNA repair is also a process that encompasses so much of what single molecule studies benefit – searching for targets, complex formation, sequential biochemical reactions and substrate hand-off to name just a few. We discuss how single molecule biophysics is poised to transform our understanding of biological systems, in particular DNA repair.     

SENSORY BIOPHYSICS OF MARINE MAMMALS

The underwater existence of marine mammals has encouraged a variety of special biophysical adaptations to their environment. Their sensory and communication systems reflect the transmission properties of sea water. For example, vision is keen in spectra that penetrate water best, vocalization is broadband and used at the frequencies that appear to fit their activities best—the differences in sensory use match the intriguing variety of behavior observed for each species. To date most of the observations of animal interactions with their marine environment have dealt with sound. There has been some work on vision and studies are underway to determine animal sensitivities to hydrodynamic pressure, chemical traces and magnetic fields. The species that have been recorded to date are listed and vocalizations are generally compared. Methods for observation of sensory mechanisms are noted along with a discussion of other aspects of marine mammal biophysics including vibrissal sensation and the biophysics of movement in a fluid environment.     

医药类高等院校生物物理课程建设的思考

医用生物物理学是研究生命物质的物理性质,生命过程的物理和物理化学规律以及物理因素对生物系统作用机制的科学,是物理学和生物学相结合而产生的一门边缘学科。在促进物理学和生命科学进步方面都显现出强大的生命力和推动力。基于医用生物物理学发展和我校学科建设发展的现实需要,本文讨论了我校建设医用生物物理学必修课或者选修课的必要性,并从本课程和学校学生特点两个方面考虑,对该课程建设的内容进行了初步的整合。旨在对教学内容进行整合、优化,增加一些新概念、新知识及前沿动态,把新旧知识联系到了一起,教会学生如何应用基础知识解决问题的方法以及缓解目前学时少、内容多这一矛盾。     

Q & A. [interview

George Oster is Professor of Biophysics, University of California, Berkeley. He received his B.S. at the U.S. Merchant Marine Academy and his Ph.D. at Columbia University. He began his career in biophysics as a postdoc at the Weizmann Institute under Aharon Katchalsky, where his research involved membrane biophysics and irreversible thermodynamics. His concern for environmental issues led him into population biology, which shaded into evolutionary biology and thence to developmental biology, cell biology and, most recently, protein motors and bacterial motility and pattern formation. His tools are mathematics, physics and computer simulation. He is currently a faculty member in the Departments of Molecular and Cellular Biology and the College of Natural Resources at Berkeley.     

High pressure macromolecular crystallography for structural biology: a review

In recent years, significant progress in high pressure macromolecular crystallography has been observed. It can be attributed both to the developments in experimental techniques, as well as to recognition of importance of high pressure protein studies in biochemistry and biophysics. The number of protein structures determined at pressure up to 1 GPa is growing. The unique advantages of this method can greatly improve the investigation of higher energy conformers of functional significance and our understanding of functionally important conformers, protein folding processes and the structural base of conformational diseases.     

Festschrift in the Honor of Stephen H. White��s 70th Birthday

The Symposium 'Frontiers in membrane and membrane protein biophysics: experiments and theory', held this year at the University of California, Irvine (August 19-20), celebrated the 70th Birthday of Stephen H. White by bringing together distinguished experimentalists and theoreticians to discuss the state of the art and future challenges in the field of membrane and membrane protein biophysics. The meeting and this special issue highlight the highly interdisciplinary nature of membrane and membrane protein biophysics, and the tremendous contributions that S. H. White and his lab have brought to the field.     

Determination of regions involved in amyloid fibril formation for Aβ(1-40) peptide

The studies of amyloid structures and the process of their formation are important problems of biophysics. One of the aspects of such studies is to determine the amyloidogenic regions of a protein chain that form the core of an amyloid fibril. We have theoretically predicted the amyloidogenic regions of the Aβ(1-40) peptide capable of forming an amyloid structure. These regions are from 16 to 21 and from 32 to 36 amino acid residues. In this work, we have attempted to identify these sites experimentally by the method of tandem mass spectrometry. As a result, we show that regions of the Aβ(1-40) peptide from 16 to 22 and from 28 to 40 amino acid residues are resistant to proteases, i.e. they are included in the core of amyloid fibrils. Our results correlate with the results of the theoretical prediction.     

Most of it started with T4 phage and was then taken over

Professor Fumio Arisaka is one of the famous leaders in bacteriophage research, especially in the areas of protein biophysics and structural biology. Autonomous phage morphogenesis is a self-assembly process controlled by subunit–subunit interaction. Under this principle, Fumio has studied T4 tail assembly and morphology. He has also contributed structural information about T4 phage through a combination of X-ray structural analysis and three-dimensional image reconstruction using cryo-electron microscopy. Most of the development of ultracentrifugation applications for molecular assembly and phage morphogenesis research was also performed in Fumio’s laboratory. Fumio is a pioneer of supramolecular protein assembly study, and his science continues in the research work of the approximately 150 people who had attended his final lecture at the Tokyo Institute of Technology.     

The red‐edge effects: 30 years of exploration

In 1970, three laboratories independently made a discovery that, for aromatic fluorophores embedded into different rigid and highly viscous media, the spectroscopic properties do not conform to classical rules. The fluorescence spectra can depend on excitation wavelength, and the excited‐state energy transfer, if present, fails at the ‘red’ excitation edge. These red‐edge effects were related to the existence of excited‐state distribution of fluorophores on their interaction energy with the environment and the slow rate of dielectric relaxation of this environment. In these conditions the site‐selection can be provided by variation of the energy of illuminating light quanta, and the behaviour of selected species can be followed as a function of time and other variables. These observations found extensive application in different areas of research: colloid and polymer science, molecular biophysics, photochemistry and photobiology. In particular, they led to the development of very productive methods of studying the dynamics of dielectric relaxations in protein and membranes, using the tryptophan emission and the emission of a variety of probes. These studies were extended to the time domain with the observation of new site‐selective effects in emission intensity and anisotropy decays. They stimulated the emergence and development of cryogenic energy‐selective and single‐molecular techniques that became valuable tools in their own right in chemistry and biophysics research. Site‐selection effects were discovered for electron‐transfer and proton‐transfer reactions if they depended on the dynamics of the environment. This review is focused on the progress in the field of red‐edge effects, their applications and prospects. Copyright © 2002 John Wiley & Sons, Ltd.     

Analysis of the microbial proteome

Proteomics has begun to provide insight into the biology of microorganisms. The combination of proteomics with genetics, molecular biology, protein biochemistry and biophysics is particularly powerful, resulting in novel methods to analyse complex protein mixtures. Emerging proteomic technologies promise to increase the throughput of protein identifications from complex mixtures and allow for the quantification of protein expression levels.     

The interface of protein structure, protein biophysics, and molecular evolution

Abstract The interface of protein structural biology, protein biophysics, molecular evolution, and molecular population genetics forms the foundations for a mechanistic understanding of many aspects of protein biochemistry. Current efforts in interdisciplinary protein modeling are in their infancy and the state-of-the art of such models is described. Beyond the relationship between amino acid substitution and static protein structure, protein function, and corresponding organismal fitness, other considerations are also discussed. More complex mutational processes such as insertion and deletion and domain rearrangements and even circular permutations should be evaluated. The role of intrinsically disordered proteins is still controversial, but may be increasingly important to consider. Protein geometry and protein dynamics as a deviation from static considerations of protein structure are also important. Protein expression level is known to be a major determinant of evolutionary rate and several considerations including selection at the mRNA level and the role of interaction specificity are discussed. Lastly, the relationship between modeling and needed high-throughput experimental data as well as experimental examination of protein evolution using ancestral sequence resurrection and in vitro biochemistry are presented, towards an aim of ultimately generating better models for biological inference and prediction.     

Mechanisms of protein folding

Understanding the mechanism by which a polypeptide chain folds into its native structure is a central problem of modern biophysics. The collaborative efforts of experimental and theoretical studies recently raised the tantalizing possibility to define a unifying mechanism for protein folding. In this review we summarize some of these intriguing advances and analyze them together with a discussion on the new findings concerning the so-called downhill folding.     

Program review. The Interdisciplinary Biophysics Graduate Program at the University of Michigan

The Michigan Biophysics Graduate Program (MBGP) was established in 1949, making it one of the first such programs in the world. The intellectual base of the program was significantly broadened in the 1980 when faculty members from a number of other units on campus were invited to join. Currently over forty faculty members from a variety of disciplines participate as mentors for the Ph.D. students enrolled in the MBGP providing our students with rich opportunities for academic learning and research. The MBGP has two main objectives: 1) to provide graduate students with both the intellectual and technical training in modern biophysics, 2) to sensitize our students to the power and unique opportunities of interdisciplinary work and thinking so as to train them to conduct research that crosses the boundaries between the biological and physical sciences. The program offers students opportunities to conduct research in a variety of areas of contemporary biophysics including structural biology, single molecule spectroscopy, spectroscopy and its applications, computational biology, membrane biophysics, neurobiophysics and enzymology. The MBGP offers a balanced curriculum that aims to provide our students with a strong academic base and, at the same time, accommodate their different academic backgrounds. Judging its past performance through the success of its former students, the MBGP has been highly successful, and there is every reason to believe that strong training in the biophysical sciences, as provided by the MBGP, will become even more valuable in the future both in the academic and the industrial settings. in the academic and the industrial settings.     

Conception of a Bioelectromagnetic Signal System via the Collagen Fibril Network; Biochemical Conclusions and Underlying Coherent Mechanism. II. Energetic Aspects,Acid and Neutral Proteases,and the Phenomenon of Coherence

This paper presents a bioelectrical conception of connective tissue regulation in bone, cartilage, and tendon, as well as other mechanically stressed connective tissues, based on the biological hypothesis of a biosensor and nerve-like signal conducting function of the native collagen fibril in the extracellular matrix. The various levels of existing conceptions of bioelectrical connective tissue regulation as well as some questions of classical connective tissue research (e.g., neutral and acid protease activity) are discussed from this electrophysiological point of view. Part I presented the topic in the form of classical biophysics and physicochemistry. This paper, Part II, makes use of the concept for a discussion of the “living state” of the extracellular matrix, biochemical aspects of acid and neutral protease activity, and nanoelectronic, relativistic, and coherent aspects of connective tissue regulation.