斑马鱼:在生命科学中畅游

模式动物是生命科学研究的重要材料,为生命科学的发展做出了重要的贡献。自20世纪90年代初以来,斑马鱼因其多方面的优点已成为模式动物家族中重要的一员,受到越来越多的重视和利用。目前,斑马鱼被广泛地用于发育生物学、遗传学、肿瘤学、药物学、毒理与环保等方面的研究,不断涌现新的研究成果。     

封面图片介绍

正斑马鱼(Danio rerio),属硬骨鱼纲(Osteichthyes),鲤形目(Cypriniformes),鲤科(Cyprindidae),短鱼丹属(Branchydanio)。因其体侧具有5条延伸至尾部的水平蓝色条纹而得名,斑马鱼原产于喜马拉雅东南部地区的溪流的热带淡水鱼,在科学研究中斑马鱼作为重要的脊椎动物模式生物之一,可广泛用于发育生物学、遗传生物学、细胞生物学、分子生物学、神经生物学、免疫学、药物学等方面的研究,在生命科学的发展中具有     

中国科学院模式生物发育与疾病国际研讨会（第二轮通知）

一、会议主题 模式生物（包括小鼠、爪蟾、斑马鱼、果蝇、线虫和酵母等）是现代生命科学和医学研究不可缺少的重要研究体系,是推动生命科学和医学研究发展的火车头。大会希望通过此次研讨促进模式动物发育与疾病研究重点领域的实质性交流与合作,增强我国在发育生物学和人类疾病研究领域的源头创新能力。会议组委会热诚欢迎国内外同行,特别是青年学者和学生踊跃参加。     

模式生物研究

世界上公认的用于生命科学研究的常见模式生物有酵母、线虫、果蝇、斑马鱼、小鼠、拟南芥等。当今,生命科学及医学的发展,模式生物发挥着重要作用。据统计,刊登在Nature、Science和Cell等重要杂志上的论文中,80％以上有关生命过程和机理的研究都是通过模式生物来进行的。本期《生命科学》以专题的形式,刊登了由国内从事模式生物研究专家撰写的介绍模式生物的文章。作者从不同角度,对不同模式生物在研究工作中的历史轨迹、各自优势、技术手段、热点课题、发展前景,以及对生命现象揭密和人类疾病治疗探索的重大贡献作了系统而又简要的介绍。从中,我们可以具体而又生动地体察到,模式生物在今天生命科学发展中的重要地位和推动生命科学及医学进步的不可替代的巨大潜力。改革开放以来,我国生命科学研究经历了“跟踪”、“接轨”和“融入主流领域”的过程,而用模式生物进行的研究则是主流研究领域的重要组成部分。只有通过在主流研究领域的参与、竞争、创新超越,才能提高我国生命科学研究水平,才能真正对世界生命科学的发展作出重大贡献。作为主流领域的模式生物研究,我国起步很晚,仅局限在很少数的实验室。因此,加强这方面的介绍,对于普及现代生命科学理念,大力推动模式生物研究领域的开展和学术交流,是十分重要和及时的。     

斑马鱼模型在药物筛选中的应用

斑马鱼具有子代数量多、体外受精、胚胎透明、可以做大规模遗传突变筛选等生物学特性,因此成为一种良好的脊椎动物模式生物。随着研究的深入,斑马鱼不仅应用于遗传学和发育生物学研究,而且拓展和延伸到疾病模型和药物筛选领域。作为一种整体动物模型,斑马鱼能够全面地检测评估化合物的活性和副作用,实现高内涵筛选。近年来,科学家们不断地发展出新的斑马鱼疾病模型和新的筛选技术,并找到了一批活性化合物。这些化合物大多数在哺乳动物模型中也有相似的效果,其中前列腺素E2(dmPGE2)和来氟米特(Leflunomide)已经进入临床实验,分别用来促进脐带血细胞移植后的增殖和治疗黑素瘤。这些成果显示了斑马鱼模型很适合用于药物筛选。文章概括介绍了斑马鱼模型的特点和近年来在疾病模型和药物筛选方面的进展,希望能够帮助人们了解斑马鱼在新药研发中的应用,并开展基于斑马鱼模型的药物筛选。     

斑马鱼在生命科学研究中的应用

利用模式生物进行研究是推动生命科学发展的主要手段之一.斑马鱼已成为继小鼠之后的又一个重要的模式脊椎动物.本文将重点介绍斑马鱼在学习记忆和疾病研究领域中的应用,以及我国推动斑马鱼相关研究的策略.     

斑马鱼在新药发现中的应用

在过去20年里,斑马鱼已成为一种重要的模式脊椎动物,在发育、遗传、免疫、肿瘤和毒理等诸多研究领域中被广泛应用。近年来,斑马鱼作为活体模型越来越多地应用于某些生物学过程的药物筛选。通过斑马鱼初步筛选,在药物研发初期可确定化合物的生物学活性、毒性以及副作用等。最近的研究还发现,斑马鱼不仅用于新药筛选,还可用于药物结构的优化。本文重点介绍斑马鱼在新药发现中的应用。     

生命科学研究中常用模式生物

模式生物是生命科学研究的重要材料,目前公认的用于生命科学研究的常见模式生物有噬菌体、大肠杆菌、酵母、线虫、果蝇、斑马鱼、小鼠、拟南芥等.这8种常用模式生物对生命现象的揭密和人类疾病治疗的探索等都所做出了重大贡献,对其在生命科学研究中的历史轨迹、各自优势、技术手段、热点研究、发展前景等系统而又简要的了解,有助于具体而又生动地体察到模式生物在今天生命科学发展中的重要地位和推动生命科学及医学进步的不可替代的巨大潜力.     

细胞自噬在斑马鱼中的研究进展

细胞自噬是一种维持细胞内稳态的重要方式,并被发现与许多人类疾病相关。由于其具有重大的理论研究价值和潜在应用前景,是近年来生命科学领域的热点之一。细胞自噬的功能与机制在物种间是高度保守的,对它的研究已在多种模式生物中展开。斑马鱼是一种常用的脊椎模式动物,具有影像学、遗传学和发育生物学等学科研究的优势,也可用于高通量药物筛选,是研究细胞自噬的理想材料。目前在斑马鱼中展开的细胞自噬相关研究取得了很多进展。本研究首先简要地描述了自噬的发生过程,重点综述应用于斑马鱼中的自噬检测方法,以及利用斑马鱼模型进行的与自噬相关人类疾病的研究。     

斑马鱼血液肿瘤学的研究进展

斑马鱼已经成为当今人类遗传学和血液学研究的重要模式生物之一。文章介绍了斑马鱼造血系统的基本生物学特征, 并重点阐述了斑马鱼在血液肿瘤学领域的应用和研究概况, 显示了斑马鱼在血液肿瘤学的基础和临床研究方面均有着独特的应用前景, 文章对此进行了展望。     

Zebrafish as a model system for biomedical studies

Zebrafish (Danio rerio) is now firmly recognized as a powerful research model for many areas of biology and medicine. Here, we review some achievements of zebrafish-based assays for modeling human diseases and for drug discovery and development. For drug discovery, zebrafish is especially valuable during the earlier stages of research as its represents a model organism to demonstrate a new treatment’s efficacy and toxicity before more costly mammalian models are used. This review considers some examples of known compounds which exhibit both physiological activity and toxicity in humans and zebrafish. The major advantages of zebrafish embryos consist in their permeability to small molecules added to their incubation medium and chorion transparency that enables the easy observation of the development. Assay of acute toxicity (LC₅₀ estimation) in embryos can also include the screening for developmental disorders as an indicator of teratogenic effects. We have used the zebrafish model for toxicity testing of new drugs based on phospholipid nanoparticles (e.g. doxorubicin). Genome organization and the pathways involved into control of signal transduction appear to be highly conserved between zebrafish and humans and therefore zebrafish may be used for modeling of human diseases. The review provides some examples of zebrafish application in this field.     

斑马鱼资源的开发保藏与国家斑马鱼资源中心

斑马鱼是一种新兴的脊椎模式动物。在过去的30年中,斑马鱼已被广泛应用于生命科学、健康科学、环境农业等诸多科研领域。为了满足不同的科研需要,研究人员开发和利用各种技术创建了大量的斑马鱼基因突变和转基因品系,这些品系已成为开展相关科学研究的宝贵资源。为了更好地保藏和利用这些资源,在全球范围内建设有多个规模不一的斑马鱼资源库。2012年,我国的国家斑马鱼资源中心（http：//zfish.cn）在中国科学院水生生物研究所正式成立。本文将重点介绍全球斑马鱼资源的开发和保藏情况,以及我国国家斑马鱼资源中心的最新建设进展。     

磁生物学在模式动物斑马鱼中的研究进展

磁场在生活中无处不在,为探究磁场的生物学效应,大量研究工作已经开展。斑马鱼作为新兴的模式生物,在探明磁场与生理功能关系方面具有重要作用。本文梳理了当前磁生物学在斑马鱼上的相关研究。已有研究表明磁场会导致斑马鱼生长畸形、发育延迟和细胞凋亡,影响斑马鱼的游泳行为和方向偏好,也会改变其昼夜节律,还会对生殖和免疫功能产生影响;斑马鱼可能具有不止一种的磁感应机制,除了目前已提出的磁矿石晶体模型、自由基对模型和电磁感应模型等磁感应模型外,磁场引起的DNA损伤、Ca²⁺稳态异常、微管聚合速率改变、应激反应、生物钟基因cry的表达改变等可部分解释上述现象。针对存在的生物磁感应研究中存在的参数不一和机制不清晰等问题,结合斑马鱼优势,本文提出未来斑马鱼在磁生物学研究中的潜在方向：基于斑马鱼建立磁场和生物参数可控的磁生物学研究模型;非侵入性活体追踪相关生命活动过程,可视化研究磁生物学现象;基于Cry蛋白开展磁场与生物节律关系的研究。     

Learning developmental biology has priority in the life sciences curriculum in Singapore

Singapore has embraced the life sciences as an important discipline to be emphasized in schools and universities. This is part of the nation's strategic move towards a knowledge-based economy, with the life sciences poised as a new engine for economic growth. In the life sciences, the area of developmental biology is of prime interest, since it is not just intriguing for students to know how a single cell can give rise to a complex, coordinated, functional life that is multicellular and multifaceted, but more importantly, there is much in developmental biology that can have biomedical implications. At different levels in the Singapore educational system, students are exposed to various aspects of developmental biology. The author has given many guest lectures to secondary (ages 12-16) and high school (ages 17-18) students to enthuse them about topics such as embryo cloning and stem cell biology. At the university level, some selected topics in developmental biology are part of a broader course which caters for students not majoring in the life sciences, so that they will learn to comprehend how development takes place and the significance of the knowledge and impacts of the technologies derived in the field. For students majoring in the life sciences, the subject is taught progressively in years two and three, so that students will gain specialist knowledge in developmental biology. As they learn, students are exposed to concepts, principles and mechanisms that underlie development. Different model organisms are studied to demonstrate the rapid advances in this field and to show the interconnectivity of developmental themes among living things. The course inevitably touches on life and death matters, and the social and ethical implications of recent technologies which enable scientists to manipulate life are discussed accordingly, either in class, in a discussion forum, or through essay writing.     

A call to fins! Zebrafish as a gerontological model

Among the wide variety of model organisms commonly used for studies on aging, such as worms, flies and rodents, a wide research gap exists between the invertebrate and vertebrate model systems. In developmental biology, a similar gap has been filled by the zebrafish (Danio rerio). We propose that the zebrafish is uniquely suited to serve as a bridge model for gerontology. With high fecundity and economical husbandry requirements, large populations of zebrafish may be generated quickly and cheaply, facilitating large-scale approaches including demographic studies and mutagenesis screens. A variety of mutants identified in such screens have led to modelling of human disease, including cardiac disorders and cancer. While zebrafish longevity is at least 50% longer than in commonly used mouse strains, as an ectothermic fish species, its life span may be readily modulated by caloric intake, ambient temperature and reproductive activity. These features, coupled with a growing abundance of biological resources, including an ongoing genome sequencing project, make the zebrafish a compelling model organism for studies on aging.     

Real‐time imaging and genetic dissection of host–microbe interactions in zebrafish

Many aspects of host interactions with microbes can only be studied in the context of a whole organism. The zebrafish as a model organism has shown to be highly successful for studies of infection biology and the interactions of commensal microbiota with their hosts. Zebrafish are transparent during embryo and larval development and these early life stages are optimally suited for high‐resolution imaging of host–microbe interactions in a vertebrate organism. This is facilitated by the development of a variety of fluorescent reporter lines that mark different immune cell types or subcellular compartments where pathogens reside. The zebrafish is an excellent vertebrate model for forward genetic screening and efficient tools for gene knock‐down and targeted mutagenesis add further to the strength of this model organism. The use of zebrafish larvae for studying microbial infections has recently led to important new insights in host defence mechanisms, which are highlighted in this review focused on bacterial pathogens. Considering the highly conserved nature of the processes involved, including innate immune recognition, immunometabolism and autophagy, it is to be expected that these recent findings in zebrafish will have great translational value for biomedical applications.     

The zebrafish as a model for gastrointestinal tract–microbe interactions

The zebrafish (Danio rerio) has become a widely used vertebrate model for bacterial, fungal, viral, and protozoan infections. Due to its genetic tractability, large clutch sizes, ease of manipulation, and optical transparency during early life stages, it is a particularly useful model to address questions about the cellular microbiology of host–microbe interactions. Although its use as a model for systemic infections, as well as infections localised to the hindbrain and swimbladder having been thoroughly reviewed, studies focusing on host–microbe interactions in the zebrafish gastrointestinal tract have been neglected. Here, we summarise recent findings regarding the developmental and immune biology of the gastrointestinal tract, drawing parallels to mammalian systems. We discuss the use of adult and larval zebrafish as models for gastrointestinal infections, and more generally, for studies of host–microbe interactions in the gut.     

Plant molecular biology in China: Opportunities and challenges

In the 21st century, mankind has witnessed great advances in life sciences, including completion of theArabidopsis thaliana genome sequence and major advances with the rice genome. But, along with global economic development, urbanization, and depletion of natural resources, many serious problems are emerging (for example, environment, food, population, energy), which reinforce the need for sustainable development in many countries and in many institutions and prompt progress in life sciences globally. Plants offer the globe its only renewable resource of food, building material, and energy. Plants have highly sophisticated, concerted, short- and long-term adaptive mechanisms to the environment. Plants have great importance in global sustainable economic development. Plant molecular biology is a most essential and powerful tool in this process. Globally, plant molecular biology research is progressing rapidly, from use of model plants to cereal crops and from cellular processes to evolutionary mechanisms. Results of these studies have value in ecosystem regulation and environmental phytoremediation. China is a large agricultural country with one-fifth of the world's population. The gap for the level of plant molecular biology research in China is large, compared with that in other developed nations. However, some Chinese laboratories (notably those of academicians Jiayang Li, Zhihong Xu, Zhensheng Li, Mengmin Hong, Qifa Zhang and professors Yonbiao Xue, Shouyi Chen, and Zhen Zhu) have kept pace with international developments in plant molecular biology. How to fully utilize plant biodiversity in China requires future advances in plant molecular biology. This minireview discusses opportunities and challenges in plant molecular biology in China, analyzes the current status of international plant molecular biology, and provides suggestions to accelerate and advance international efforts. These authors contributed to this paper equally. Editorial note: This paper, with minor editing, is as it was presented by the authors at the Genetics Advancing Meeting of the Chinese Society of Genetics, Xiamen University, China, 13–17 May 2004.     

The Tiny Zebrafish Keep Swimming Fast in the Developmental Biology Pond

In 1996,the journal Development published a special issue on zebrafish solely focusing on characterization of dozens of phenotypic mutants chosen from hundreds of mutants identified through chemical(ENU)mutagenesis by two zebrafish groups in Tubingen and Boston.This milestone formally catapulted zebrafish to a league of genetically tractable model