Cloning Expeditions: Risky but Rewarding

In the 1980s, a good part of my laboratory was using the then-new recombinant DNA techniques to clone and characterize many important cell surface membrane proteins: GLUT1 (the red cell glucose transporter) and then GLUT2 and GLUT4, the red cell anion exchange protein (Band 3), asialoglycoprotein receptor subunits, sucrase-isomaltase, the erythropoietin receptor, and two of the subunits of the transforming growth factor β (TGF-β) receptor. These cloned genes opened many new fields of basic research, including membrane insertion and trafficking of transmembrane proteins, signal transduction by many members of the cytokine and TGF-β families of receptors, and the cellular physiology of glucose and anion transport. They also led to many insights into the molecular biology of several cancers, hematopoietic disorders, and diabetes. This work was done by an exceptional group of postdocs and students who took exceptionally large risks in developing and using novel cloning technologies. Unsurprisingly, all have gone on to become leaders in the fields of molecular cell biology and molecular medicine.     

Interface Biology of Implants

Implants are widely used in various clinical disciplines to replace or stabilize organs. The challenge for the future is to apply implant materials to specifically control the biology of the surrounding tissue for repair and regeneration. This field of research is highly interdisciplinary and combines scientists from technical and life sciences disciplines. To successfully apply materials for regenerative processes in the body, the understanding of the mechanisms at the interface between cells or tissues and the artificial material is of critical importance. The research focuses on stem cells, design of material surfaces, and mechanisms of cell adhesion. For the third time around 200 scientists met in Rostock, Germany for the international symposium “Interface Biology of Implants.” The aim of the symposium is to promote the interdisciplinary dialogue between the scientists from the different disciplines to develop smart implants for medical use. In addition, researchers from basic sciences, notably cell biology presented new findings concerning mechanisms of cell adhesion to stimulate research in the applied field of implant technology.Key words: interface, implant, stem cells, adhesion, mechanics, surface, biomaterialMedical implants play a growing role in routine clinical practice. In addition to replace or stabilize injured tissue permanently or transiently, the application of implant materials to stimulate the regeneration of tissue is becoming a challenge in the field of regenerative medicine. The use of implant materials is based on the idea that biomaterials function not only as mechanical support for cells and tissue but also provide a matrix to induce signal transduction in the cells that control complex molecular mechanisms responsible for proliferation und differentiation. In this context, the interface between artificial materials and living cells or tissue is an exciting field of great scientific interest and constitutes one of the most dynamic and expanding field in science and technology. Progress in this field is mainly driven by the fundamental importance for clinical applications. The research is characterized by a multidisciplinary collaboration between physics, engineers, biologists and clinicians.In May 2009, for the third time after 2003 and 2006 around 200 scientists met in Rostock-Warnemünde for the symposium “Interface Biology of Implants” to discuss biointerface processes at a fundamental level. The main goals of this symposium are to simulate the interdisciplinary dialogue between scientists of the different disciplines and to introduce current knowledge of basic research in cell biology and material science into the applied field of implant technology. The programme was organized in invited presentations of 20 internationally renowned scientists and complemented by short talks of mostly young scientists selected from the submitted abstracts. In addition, 80 posters presented latest results in this multidisciplinary field.The symposium was opened with a keynote lecture presented by Hartmut Hildebrand (Lille). He gave an overview about the 7,000 years old history of application of implant materials. Rare photographs were shown which demonstrated that in these early times prostheses mainly made from metallic materials were used to restore teeth, extremities and the skull of the human body. These old documents stressed the historical relevance of medical application of implant materials.The symposium on two days was composed of four sessions covering the interdisciplinary research in the field. The session “Stem cells and biomaterials” discussed the biological response and signalling mechanism of stem cells in the interaction with a material surface. The session “Bioactivation of implant surfaces” focussed on the tailoring of surfaces to control the cell physiology. To stimulate the field by recent data in basic cell biology, talks were presented in the third session, dealing with molecular mechanisms involved in cell adhesion. A special session dealt with the role and mechanism of controlling cells by mechanics.     

UNVEILing connections between genotype,phenotype, and fitness in natural populations

Understanding the links between genetic variation and fitness in natural populations is a central goal of evolutionary genetics. This monumental task spans the fields of classical and molecular genetics, population genetics, biochemistry, physiology, developmental biology, and ecology. Advances to our molecular and developmental toolkits are facilitating integrative approaches across these traditionally separate fields, providing a more complete picture of the genotype‐phenotype map in natural and non‐model systems. Here, we summarize research presented at the first annual symposium of the UNVEIL Network, an NSF‐funded collaboration between the University of Montana and the University of Nebraska, Lincoln, which took place from the 1st to the 3rd of June, 2018. We discuss how this body of work advances basic evolutionary science, what it implies for our ability to predict evolutionary change, and how it might inform novel conservation strategies.     

Advances in purine and pyrimidine metabolism in health and diseases

ABSTRACT

In June, 2015, the Purine and Pyrimidine Society organized the 16th biennial symposium on Purine and Pyrimidine metabolism at the Faculty House of Columbia University, New York City. This exciting meeting focused on these important molecules, new developments in inborn errors of metabolism; therapeutic analogs. In addition, the biochemistry of mammalian and non-mammalian systems were discussed. Due to significant advances in molecular medicine, the boundaries between clinical and basic sciences have merged into exciting translational research, of which a small portion was highlighted in the presymposium.     

Lipid classification, structures and tools

The study of lipids has developed into a research field of increasing importance as their multiple biological roles in cell biology, physiology and pathology are becoming better understood. The Lipid Metabolites and Pathways Strategy (LIPID MAPS) consortium is actively involved in an integrated approach for the detection, quantitation and pathway reconstruction of lipids and related genes and proteins at a systems-biology level. A key component of this approach is a bioinformatics infrastructure involving a clearly defined classification of lipids, a state-of-the-art database system for molecular species and experimental data and a suite of user-friendly tools to assist lipidomics researchers. Herein, we discuss a number of recent developments by the LIPID MAPS bioinformatics core in pursuit of these objectives.     

Meeting Report: 1st International Symposium on Sponge Microbiology

The success of the 1st International Symposium on Sponge Microbiology reflects the growing interest of the scientific community in this new and emerging field. Research themes of the symposium included symbiont diversity, physiology and function, secondary metabolites, metagenomics, single-cell genomics and other -omics approaches, sponge–symbiont interactions, sponge diseases, environmental stress, and many more. This article summarizes the major developments in the field and identifies future foci for research.     

A conference report from "Down Under": Talking autophagy at OzBio2010

OzBio2010 was held at the Melbourne Convention and Exhibition Centre, September 26 to October 1, 2010. This international conference catered to researchers in several fields having complementary interests including biochemistry, molecular biology, cell biology, plant physiology and health-related research. It was held under the auspices of two major international scientific societies, IUBMB and FAOBMB, and the ComBio2010 collective (representing nine professional societies and groupings from Australia). A number of pre-eminent speakers presented at plenary sessions and in a wide array of specialist symposia. One of the plenary sessions and a specialist symposium highlighted autophagy-related topics.     

Advanced fluorescence technologies help to resolve long-standing questions about microbial vitality

Advances in fundamental physical and optical principles applied to novel fluorescence methods are currently resulting in rapid progress in cell biology and physiology. Instrumentation devised in pioneering laboratories is becoming commercially available, and study findings are now becoming accessible. The first results have concerned mainly higher eukaryotic cells but many more developments can be expected, especially in microbiology. Until now, some important problems of cell physiology have been difficult to investigate due to interactions between probes and cells, excretion of probes from cells and the inability to make in situ observations deep within the cell, within tissues and structures. These technologies will enable microbiologists to address these topics. This Review aims at introducing the limits of current physiology evaluation techniques, the principles of new fluorescence technologies and examples of their use in this field of research for evaluating the physiological state of cells in model media, biofilms or tissue environments. Perspectives on new imaging technologies, such as super-resolution imaging and non-linear highly sensitive Raman microscopy, are also discussed. This review also serves as a reference to those wishing to explore how fluorescence technologies can be used to understand basic cell physiology in microbial systems.     

A bird's-eye view on the modern genetics workflow and its potential applicability to the locust problem

Genetics is an immense science and the current developments in its methods and techniques as well as the fast emerging tools make it one of the most powerful biological sciences. Indeed, from taxonomy and ecology to physiology and molecular biology, every biological science makes use of genetics techniques and methods at one time or another. In fact, development in genetics is such that it is now possible to characterize and analyze the expression of the whole set of genes of virtually every living organism, even if it is a non-model one. Locusts are notorious for the damage they cause to the ecosystems and economies of the areas affected by their recurrent population outbreaks. To prevent and deal with these outbreaks, we now count on both biological as well as chemical agents that are proving to be successful in reducing the damage that otherwise locust population outbreaks might cause. However, a better, efficient and environmentally friendly solution is still a hoped-for target. In my opinion, the ideal future pesticide should be both environmentally friendly, risk free and species-specific. To reach the knowledge needed for the development of such species-specific anti-locust agent, deep and accurate knowledge of the locusts’ genetics and molecular biology is a must. Since genes and their expression levels lie at the bottom of every biological phenomenon, any species-specific solution to the locust problem requires a good knowledge of these organisms’ genes as well as the quantitative and spatio-temporal dynamics of their expression. To reach such knowledge, collaborative work is needed as well as a clear workflow that, given the fast development in the genetics tools, is not always clear to all research groups. For this reason, here I describe a genetics workflow that should allow taking advantage of the most recent genetics tools and techniques to answer question relating to locust biology. My hope is that the adoption of this and other work strategies by different research groups, especially when the work is a collaborative one, would provide precious information on the biology and the biological phenomena that these economically important organisms exhibit.     

Molecular and cellular biology of pneumococcal infection

The complete pneumococcal genome sequence was released in November, 1997. This advance has been combined with new understanding of physiology and pathogenesis including characterization of a family of surface proteins adducted to choline, regulation of virulence, and the regulon for natural DNA transformation. These developments in our understanding of molecular and cellular biology of pneumococcal infection will allow the development of new vaccines and antibiotics against this community acquired pathogen.     

对我国分子生态学研究近期发展战略的一些思考

分子生态学是多学科交叉的整合性研究领域, 是运用进化生物学理论解决宏观生物学问题的科学。经过半个多世纪的发展, 本学科已日趋成熟, 它不仅已经广泛渗透到宏观生物学的众多学科领域, 而且已经成为连接和融合很多不同学科的桥梁, 是目前最具活力的研究领域之一。其研究的范畴, 从最基础的理论和方法技术, 到格局和模式的发现和描述, 到对过程和机制的深入探讨, 再到付诸于实践的行动和规划指导等各个层次。分子生态学的兴起给宏观生物学带来了若干飞跃性的变化, 使宏观生物学由传统的以观察、测量和推理为主的描述性研究转变为以从生物和种群的遗传构成的变化和历史演化背景上检验、证明科学假设及揭示机制和规律为主的机制性/解释性研究, 因而使得对具有普遍意义的科学规律、生态和进化过程及机制的探索成为可能。分子生态学已经进入组学研究时代, 这使得阐明复杂生态过程、生物地理过程和适应性演化过程的机制性研究由原来难以企及的梦想变成完全可以实现的探求; 它也带来了全新的挑战, 其中最有深远影响的将是对分子生态学研究至关重要的进化生物学基础理论方面的突破, 例如遗传变异理论、种群分化理论、表观遗传因素的作用, 乃至进化生物学的基本知识构架等等。这些方面的进展必将使宏观生物学迎来一场空前的革命, 并对生态学的所有分支学科产生重大影响, 甚至催生诸如生态表观组学这样的新分支学科。对于中国科学家来说, 分子生态学组学时代的开启, 更是一个千载难逢的机遇, 为提出和建立生命科学的新方法、新假说、新思想和新理论提供了莫大的探索空间——此前我们对宏观生物学方法、理论和思想的发展贡献很小。然而, 限制组学时代重大突破的关键因素是理论、概念、理念、实验方法或分析方法方面的创新和突破, 这正是我国分子生态学研究最薄弱的环节。我国教育部门应尽快调整生命科学本科生培养的理念和方法, 以培养具备突出创新潜力的年轻一代后备人才; 同时, 科研项目资助部门和研究人员不仅应清醒地认识本学科领域的发展态势, 更要及时调整思路, 树立新的项目管理理念和治学 理念。     

Distribution and function of prostanoid receptors: studies from knockout mice

Recent developments in the molecular biology of the prostanoid receptors has allowed the investigation of the physiological roles of each individual receptor type and subtype. The following article reports the prostanoid receptor distributions deduced from Northern blot and in situ hybridization analyses, summarizes the phenotypes of each receptor knockout mice, and discusses recent studies investigating the effects of each receptor deficiency on the inflammatory response and female reproductive processes. The combination of expression pattern and knockout analyses enabled us to determine which receptor expressed in a particular cell is important for the maintenance of normal and/or pathological physiology. The results from these analyses may be useful in the development of novel therapeutics that can selectively manipulate prostanoid-mediated actions.     

Emerging structural biology of lipid G protein‐coupled receptors

The first crystal structure of a G protein‐coupled receptor (GPCR) was that of the bovine rhodopsin, solved in 2000, and is a light receptor within retina rode cells that enables vision by transducing a conformational signal from the light‐induced isomerization of retinal covalently bound to the receptor. More than 7 years after this initial discovery and following more than 20 years of technological developments in GPCR expression, stabilization, and crystallography, the high‐resolution structure of the adrenaline binding β₂‐adrenergic receptor, a ligand diffusible receptor, was discovered. Since then, high‐resolution structures of more than 53 unique GPCRs have been determined leading to a significant improvement in our understanding of the basic mechanisms of ligand‐binding and ligand‐mediated receptor activation that revolutionized the field of structural molecular pharmacology of GPCRs. Recently, several structures of eight unique lipid‐binding receptors, one of the most difficult GPCR families to study, have been reported. This review presents the outstanding structural and pharmacological features that have emerged from these new lipid receptor structures. The impact of these findings goes beyond mechanistic insights, providing evidence of the fundamental role of GPCRs in the physiological integration of the lipid signaling system, and highlighting the importance of sustained research into the structural biology of GPCRs for the development of new therapeutics targeting lipid receptors.     

Exploring frontiers in the DNA landscape: an introduction to the symposium "Genome Analysis and the Molecular Systematics of Retroelements"

The emerging field of phylogenomics is influencing both the amount and type of characters being brought to bear on long-standing problems in systematic biology. Moreover, the proliferation of sequence information from genome projects in concert with the development of new informatics tools is widening access to comparative data on retroelements to a broad cross section of investigators. Motivated by this, the Society of Systematic Biologists sponsored a symposium entitled "Genome Analysis and the Molecular Systematics of Retroelements," and the resulting papers illustrate this theme of new discoveries and cover three basic areas of research: (i) the taxonomic distribution and phylogenetic structure of families of retroelements; (II) the use of SINE and LINE insertions for phylogenetic inference; and (III) the informatics and classification of repetitive elements. Contributions of each article are briefly discussed in this context and particularly fruitful directions for future research illuminated by results of this symposium are reviewed.     

Gene expression signatures in primary immunodeficiencies: the experience from human disease and mouse models

Extensive research on molecular genetics in recent decades has provided a wealth of information regarding the underlying mechanisms of primary immunodeficiency diseases. The microarray technology has made its entry into the molecular biology research area and hereby enabled signature expression profiling of whole species genomes. Perhaps no other methodological approach has transformed molecular biology more in recent years than the use of microarrays. Microarray technology has led the way from studies of the individual biological functions of a few related genes, proteins or, at best, pathways towards more global investigations of cellular activity. The development of this technology immediately yielded new and interesting information, and has produced more data than can be currently dealt with. It has also helped to realize that even a 'horizontally exhaustive' molecular analysis is insufficient. Applications of this tool in primary immunodeficiency studies have generated new information, which has led to a better understanding of the underlying basic biology of the diseases. Also, the technology has been used as an exploratory tool to disease genes in immunodeficiency diseases of unknown cause as in the case of the CD3Delta-chain and the MAPBPIP deficiency. For X-linked agammaglobulinemia, the technique has provided better understanding of the genes influenced by Btk. There is considerable hope that the microarray technology will lead to a better understanding of disease processes and the molecular phenotypes obtained from microarray experiments may represent a new tool for diagnosis of the disease.     

Gonadotropin-releasing hormone: molecular and cell biology, physiology, and clinical applications

The observations in recent years that gonadotropin-releasing hormone ( pyroGlu1 -His2-Trp3- Ser4 -Tyr5- Gly6 -Leu7-Arg8-Pro9- G ly10NH2 [GnRH]) has considerable clinical efficacy as a contraceptive, an ovulation-inducing agent, and a drug that is useful in the therapy of a number of diseases are owed in no small part to advances that have been made in the basic molecular biology and physiology of this peptide. It is reasonable then that this symposium should be broken down into three separate yet integrated areas: 1) the molecular and cellular biology of GnRH, 2) the physiology of GnRH, and 3) the clinical efficacy of this compound. A number of recent advances have helped the progress of work in all three of these areas. The observation that substitution of a D-amino acid in the sixth amino acid position leads to considerable metabolic stability and reduced degradation of releasing hormone analogs has been especially useful. In addition, the observation that the further derivatization of such substituted compounds by deletion of the 10th amino acid and addition of an ethylamide group to Pro9 has resulted in compounds with a markedly increased ability to bind to the receptor. These compounds have been useful clinically and have allowed development of radioligand assays to be used in animal studies and in vitro. The availability of a large number of agonists and antagonists has allowed formulation of molecular models for GnRH and resulted in development of clinically useful compounds. In a short paper of this nature we cannot hope to provide an encyclopedic review; rather we hope to provide an overview and offer references to the literature for those who wish a more in-depth treatment.     

Production of useful secondary metabolites in plants: Functional genomics approaches

The paradigm of biological research has been changed by recent developments in genomics, high-throughput biology, and bioinformatics. Conventional biology often was based on empirical, labor-intensive, and time-consuming methods. In the new paradigm, biological research e is driven by a holistic approach on the basis of rational, automatic, and high-throughput methods. New functional compounds can be discovered by using high-throughput screening systems. Secondary metabolite pathways and the genes involved in those pathways are then determined by studying functional genomics in conjunction with the data-mining tools of bioinformatics. In addition, these advances in metabolic engineering enable researchers to confer new secondary metabolic pathways to crops by transferring three to five, or more, heterologous genes taken from various other species. In the future, engineering for the production of useful compounds will be designed by a set of software tools that allows the user to specify a cell’s genes, proteins, and other molecules, as well as their individual interactions.     

Effects of cyanobacterial extracellular products and gibberellic acid on salinity tolerance in Oryza sativa L

The XI International Rotifer Symposium was held during 11–18 March, 2006 at the National Autonomous University of Mexico Campus Iztacala located at the North Mexico City (Mexico). These triennial international meetings, first organized in Austria by Late Ruttner-Kolisko in September 1976, are gradually becoming the focal point of discussion and collaboration from rotifer workers across the world. The present XI symposium was attended by 125 participants from 20 nations. During this meeting, different themes of rotifer research from morphology to molecular biology were considered. In addition, there were four invited lectures and four workshops covering different themes of the symposium. During the last 30 years, rotifer research has witnessed gradual shift from the conventional morphological taxonomy to molecular and evolutionary systematics. While the basic rotifer ecological studies continue today, applied areas such as ecotoxicology and aquaculture have taken key roles in the recent meetings. The international rotifer meetings provide ample opportunities not only for exchange of ideas and recent research, but also for material and in establishing inter-personal relationships. Over the last 30 years, the number of participants attending the rotifer meetings has increased.