Advances in biotechnology and linking outputs to variation in complex traits: Plant and Animal Genome meeting January 2012

The Plant and Animal Genome (PAG, held annually) meeting in January 2012 provided insights into the advances in plant, animal, and microbe genome studies particularly as they impact on our understanding of complex biological systems. The diverse areas of biology covered included the advances in technologies, variation in complex traits, genome change in evolution, and targeting phenotypic changes, across the broad spectrum of life forms. This overview aims to summarize the major advances in research areas presented in the plenary lectures and does not attempt to summarize the diverse research activities covered throughout the PAG in workshops, posters, presentations, and displays by suppliers of cutting-edge technologies.     

Advances in genome studies: the PAG 2010 conference

An overview is provided of the advances in plant, animal and human genome studies by summarizing the contents of seven plenary lectures presented at the Plant and Animal Genome (PAG) meeting in January 2010. The area of biology covered was wide and reflected the nature of this fast moving science.     

Convergence of human pluripotent stem cell,organoid, and genome editing technologies

The last decade has seen many exciting technological breakthroughs that greatly expanded the toolboxes for biological and biomedical research, yet few have had more impact than induced pluripotent stem cells and modern-day genome editing. These technologies are providing unprecedented opportunities to improve physiological relevance of experimental models, further our understanding of developmental processes, and develop novel therapies. One of the research areas that benefit greatly from these technological advances is the three-dimensional human organoid culture systems that resemble human tissues morphologically and physiologically. Here we summarize the development of human pluripotent stem cells and their differentiation through organoid formation. We further discuss how genetic modifications, genome editing in particular, were applied to answer basic biological and biomedical questions using organoid cultures of both somatic and pluripotent stem cell origins. Finally, we discuss the potential challenges of applying human pluripotent stem cell and organoid technologies for safety and efficiency evaluation of emerging genome editing tools.     

Multiscale modelling of chromatin organisation: Resolving nucleosomes at near-atomistic resolution inside genes

The three-dimensional organisation of the genome modulates biological processes and is, in turn, transformed by the activity in the nucleus. Not surprisingly, understanding how the genome operates requires uncovering the fundamental biophysical and molecular mechanisms that establish and regulate its organisation. Genome organisation starts with the formation of chromatin: a polymer of nucleoprotein complexes, termed nucleosomes, that carry variable chemical signatures according to their biological context. The physicochemical heterogeneity of chromatin, the stochastic organisation it fosters, and the multiscale nature of genome organisation pose great technical challenges. Excitingly, advances in imaging and molecular biology techniques are addressing chromatin organisation at increasing resolutions. In tandem, computer models are testing and postulating hypotheses, interpreting the experimental data, and linking molecular properties of nucleosomes to the mesoscale organisation of chromatin. We discuss how coarse-grained models at varying resolutions are expanding our mechanistic understanding of chromatin organisation, and the challenges still remaining in the field.     

Advances in quantitative proteomics using stable isotope tags

A great deal of current biological and clinical research is directed at the interpretation of the information contained in the human genome sequence in terms of the structure, function and control of biological systems and processes. Proteomics, the systematic analysis of proteins, is becoming a critical component in this endeavor because proteomic measurements are carried out directly on proteins – the catalysts and effectors of essentially all biological functions. To detect changes in protein profiles that might provide important diagnostic or functional insights, proteomic analyses necessarily have to be quantitative. This article summarizes recent technological advances in quantitative proteomics.     

Improved understanding of the interactions and complexities of biological nitrogen and phosphorus removal processes

Nitrogen and phosphorus removal from wastewater is now considered essential for the protection of our waterways. Biological nutrient removal processes are generally the most efficient and cost-effective solution to achieve this. While the principles of these processes are well known, intriguing and useful details are being discovered with the recent advances in bio-process engineering and microbial sciences. Phosphorus accumulating organisms have only been identified in recent years, and there are now competing glycogen accumulating organisms being found in biological phosphorus removal systems. These can possibly explain the reasons for the variable phosphorus removal performance of certain systems, and their control can help in the development of more stable and better performing processes. Detailed investigations of the traditional nitrification-denitrification systems, but also of novel developments for nitrogen removal, reveal a more complex and diverse range of processes involved in these transformations. Increasingly, linked phosphorus and nitrogen removal processes are being developed, creating further opportunities to optimise the technologies. However, this might also bring certain risks such as the potential to produce the greenhouse-gas nitrous oxide (N₂O) rather than nitrogen gas as the final denitrification product. A range of recent developments in these areas is covered in this paper.     

植物可溶性N-乙基马来酰亚胺敏感因子连接物复合体(SNAREs)及其生物学功能研究进展

在真核生物细胞中, 各细胞器间物质和信息的交流是细胞生命活动的基本保证, 而囊泡转运是细胞器之间物质和信息交流的主要方式。大多数的囊泡融合过程是由可溶性的N-乙基马来酰亚胺敏感因子连接物复合体(Soluble N-ethyl-maleimide-sensitive fusion protein attachment protein receptors, SNAREs)介导的, 物种间的SNAREs具有高度保守的特性。与其他真核生物相比, 植物的基因组编码更多的SNAREs。研究证明, 植物的SNAREs是一个多功能的蛋白家族, 在植物的许多生理过程中都有着重要的作用。本文对植物SNAREs作用的分子机理及生物学功能的最新研究进展做一概述。     

Quantitative evolution of transposable and satellite DNA sequences in Picea species

Clones containing tandemly arranged repeats belonging to two distinct sequence families, (i) PAG004P22F (2F) and PAG004E03C (3C) or (ii) Ty3/gypsy- (8R; PAG004B08R) and Ty1/copia-like sequences (9R; PAG007F19R), were selected from a randomly sheared total genomic DNA library of Picea abies . The inserts were used as probes in dot-blot hybridizations to genomic DNA of P. abies, Picea orientalis , Picea pungens , and Picea pungens var. glauca. All these entities are diploid and share the same chromosome number (2n = 24), but the genome sizes differ largely. The redundancy (copy number per 1C DNA) of sequences related to each probe varied greatly between the genomes. No significant correlation was found between the genome size and the copy number of sequences in any family. The quantitative ratios varied greatly (in each genome) between the two families of satellite DNA, between the sequences that represented copia or gypsy retrotransposons, and between tandemly arranged sequences and retroelements as a whole, suggesting that there is no common factor that controls the quantitative evolution of repeats belonging to different sequence families during speciation in Picea.     

The International Conference on Intelligent Biology and Medicine (ICIBM) 2016: putting systems biology to work

Between December 8–10, 2016, the International Conference on Intelligent Biology and Medicine (ICIBM 2016) was held in Houston, Texas, USA. The conference included eight scientific sessions, four tutorials, one poster session, four highlighted talks and four keynotes that covered topics in 3D genome structure analysis and visualization, next generation sequencing analysis, computational drug discovery, medical informatics, cancer genomics and systems biology. Systems biology has been a main theme in ICIBM 2016, with exciting advances were presented in many areas of systems biology. Here, we selected seven high quality papers to be published in BMC Systems Biology.     

蛋白质与抗体微阵列及其在生物医学研究中的应用

随着人类基因组测序的顺利完成及其他相关领域如机械制造、微电子加工技术及生物信息学方面所取得的进展,以蛋白质为研究对象的蛋白质组学愈显重要,高通量的蛋白质与抗体阵列芯片分析技术正日益为人们关注.对蛋白质分析策略及以阵列为基础的蛋白质芯片分析原理、相关的制备方法与检测技术及其在生物学研究、医学与实验诊断应用方面进行了阐述,并对现阶段该技术存在的不足与发展前景进行了讨论.     

Corticofugal projections to the periaqueductal gray matter in the cat midbrain

Stereotaxic microinjections of horseradish peroxidase (HP) were made into different parts of the rostral and caudal periaqueductal gray (PAG) in cats to study corticofugal projections to the PAG. The method of retrograde axonal transport of HP demonstrated labeled neurons in the I and II somatosensory areas, frontal, cingular and insular cortex of the brain. It was shown that the II somatosensory cortex projects to all the areas of the rostral and caudal PAG. The frontal cortex projects to the dorsolateral quadrant of the PAG. The findings obtained enabled the detection of the morphological substrate of the corticofugal effects on one of the antinociceptive brain structures--the PAG.     

Interpreting human genetic variation with in vivo zebrafish assays

Rapid advances and cost erosion in exome and genome analysis of patients with both rare and common genetic disorders have accelerated gene discovery and illuminated fundamental biological mechanisms. The thrill of discovery has been accompanied, however, with the sobering appreciation that human genomes are burdened with a large number of rare and ultra rare variants, thereby posing a significant challenge in dissecting both the effect of such alleles on protein function and also the biological relevance of these events to patient pathology. In an effort to develop model systems that are able to generate surrogates of human pathologies, a powerful suite of tools have been developed in zebrafish, taking advantage of the relatively small (compared to invertebrate models) evolutionary distance of that genome to humans, the orthology of several organs and signaling processes, and the suitability of this organism for medium and high throughput phenotypic screening. Here we will review the use of this model organism in dissecting human genetic disorders; we will highlight how diverse strategies have informed disease causality and genetic architecture; and we will discuss relative strengths and limitations of these approaches in the context of medical genome sequencing. This article is part of a Special Issue entitled: From Genome to Function.     

Genome-wide RNAi as a route to gene function in Drosophila.

With the sequencing of the human genome and the genomes of most major model organisms completed, the systematic characterisation of gene functions remains a key challenge. During the past few years, RNA interference (RNAi) has become a powerful tool to silence the expression of genes and analyse their loss-of-function phenotype when mutant alleles are not available. Genome-wide RNAi screens against all predicted genes have been successfully used to dissect a variety of biological processes in Caenorhabditis elegans. Recently, a genome-wide library of double-stranded RNAs, that target every gene in the Drosophila genome and that is suitable for high throughput cell-based assays, was published. In this paper, recent advances will be summarised. Screening strategies and applications as a route to comprehensively characterising gene function will be discussed.     

Molecular insights into the initiation of sporulation in Gram-positive bacteria: new technologies for an old phenomenon

The last decade has witnessed extensive, and widespread, changes in scientific technologies that have impacted significantly upon the study of the life sciences. Arguably, the biggest advances in our comprehension of simple and complex biological processes have come as a consequence of obtaining the complete DNA sequence of organisms. It is likely that we will become accustomed to hearing of quantum leaps in the study and understanding of the biology of higher eukaryotes in the coming years, now that (near) complete genome sequences are available for man, mouse and rat. In this review, we will discuss the impact of genome sequence data, and the use of new scientific technologies that have emerged largely as consequence of the availability of this information, on the study of the master regulator of sporulation, Spo0A, in low G+C Gram-positive endospore-forming bacteria.     

Fluorescent oligo and poly-thiophenes and their utilization for recording biological events of diverse origin—when organic chemistry meets biology

The technique of using luminescent oligo-thiophenes and luminescent conjugated poly-thiophenes to monitor biological processes has gained increased interest from scientists within different research areas, ranging from organic chemistry and photo-physics to biology since its introduction. The technique is generally straightforward and requires only standard equipment, and the result is available within minutes from sample preparation. In this review, the syntheses of oligo and polythiophenes developed over the last decades are discussed. Furthermore, the utilization of these molecular agents for exploring biological events, e.g., DNA hybridization or protein misfolding events, are covered.     

Genome comparisons and analysis

As we enter the post-genomic era, with the accelerating availability of complete genome sequences, new theoretical approaches and new experimental techniques, our ability to dissect cellular processes at the molecular level continues to expand. Recent advances include the application of RNA interference methods to characterize loss-of-function phenotype genes in higher eukaryotes, comparative analysis of the human and mouse genome sequences, and methods for reconciling contradictory phylogenetic reconstructions. New developments feed into the increasingly rich content of databases such as the COG database. The next phase of research will be increasingly dominated by efforts to integrate the deluge of data into our understanding of biological systems.     

Chemical genomics and medicinal systems biology: chemical control of genomic networks in human systems biology for innovative medicine

With advances in determining the entire DNA sequence of the human genome, it is now critical to systematically identify the function of a number of genes in the human genome. These biological challenges, especially those in human diseases, should be addressed in human cells in which conventional (e.g. genetic) approaches have been extremely difficult to implement. To overcome this, several approaches have been initiated. This review will focus on the development of a novel "chemical genetic/genomic approach" that uses small molecules to "probe and identify" the function of genes in specific biological processes or pathways in human cells. Due to the close relationship of small molecules with drugs, these systematic and integrative studies will lead to the "medicinal systems biology approach" which is critical to "formulate and modulate" complex biological (disease) networks by small molecules (drugs) in human bio-systems.     

Protein glycosylation in bacterial mucosal pathogens

In eukaryotes, glycosylated proteins are ubiquitous components of extracellular matrices and cellular surfaces. Their oligosaccharide moieties are implicated in a wide range of cell-cell and cell-matrix recognition events that are required for biological processes ranging from immune recognition to cancer development. Glycosylation was previously considered to be restricted to eukaryotes; however, through advances in analytical methods and genome sequencing, there have been increasing reports of both O-linked and N-linked protein glycosylation pathways in bacteria, particularly amongst mucosal-associated pathogens. Studying glycosylation in relatively less-complicated bacterial systems provides the opportunity to elucidate and exploit glycoprotein biosynthetic pathways. We will review the genetic organization, glycan structures and function of glycosylation systems in mucosal bacterial pathogens, and speculate on how this knowledge may help us to understand glycosylation processes in more complex eukaryotic systems and how it can be used for glycoengineering.