端粒和端粒酶的发现及其生物学意义

2009年的诺贝尔生理学或医学奖授予了美国加州大学旧金山分校的Elizabeth H．Blackburn、约翰霍普金斯大学的Carol W．Greider以及哈佛医学院的Jack W．Szostak三位科学家,肯定他们在发现端粒以及端粒酶保护染色体末端方面所做出的贡献。端粒以及端粒酶的发现历经近半个世纪,追溯起端粒和端粒酶的整个发现过程,却是耐人寻味,给人启发。端粒是真核生物中位于染色体末端的DNA和蛋白质的复合物,它对于维持基因组的完整性以及染色体的稳定性都有着至关重要的作用。端粒DNA可以被一种特化的称为“端粒酶”的逆转录酶延伸。端粒长度的维持以及端粒结构的稳定在细胞衰老、癌症发生以及干细胞全能性自我更新能力维持等生命过程中都起重要作用。     

From nerves and hormones to bacteria in the stomach; Nobel prize for achievements in gastrology during last century.

Rapid progress in gastroenterological research, during past century, was initiated by the discovery by W. Prout in early 18th century of the presence of inorganic, hydrochloric acid in the stomach and by I.P. Pavlov at the end of 19th century of neuro-reflex stimulation of secretion of this acid that was awarded by Nobel prize in 1904. Then, J. W. Black, who followed L. Popielski's concept of histamine involvement in the stimulation of this secretion, was awarded second Nobel prize in gastrology within the same century for the identification of histamine H2-receptor (H2-R) antagonists, potent gastric acid inhibitors, accelerating ulcer healing. The concept of H2-R interaction with other receptors such as muscarinic receptors (M3-R), mediating the action of acetylocholine released from local cholinergic nerves, and those mediating the action of gastrin (CCK2-R) on parietal cells, has been confirmed both in vivo studies and in vitro isolated parietal cells. The discovery of H2-R antagonists by Black and their usefulness in control of gastric secretion and ulcer healing, were considered as real breakthrough both in elucidation of gastric secretory mechanisms and in ulcer therapy. Discovery of even more powerful gastric acid inhibitors, proton pump inhibitors (PPI), also highly effective in acceleration of ulcer healing was, however, not awarded Nobel prize. Unexpectedly, two Australian clinical researchers, R.J. Warren and B.J. Marshall, who discovered in the stomach spiral bacteria, named Helicobacter pylori, received the third in past century Nobel prize in gastrology for the finding that this bacterium, is related to the pathogenesis of gastritis and peptic ulcer. They documented that eradication of H. pylori from the stomach, using antibiotics and potent gastric inhibitors, not only accelerates healing of ulcer but also prevents its recurrence, the finding considered as greatest discovery in practical gastrology during last century. Thus, the outstanding achievements in gastroenterology during last century have been awarded by three Nobel prizes and appreciated by millions of ulcer patients all over the world.     

Natural products discovery from micro-organisms in the post-genome era†

With the decision to award the Nobel Prize in Physiology or Medicine to Drs. S. ōmura, W.C. Campbell, and Y. Tu, the importance and usefulness of natural drug discovery and development have been revalidated. Since the end of the twentieth century, many genome analyses of organisms have been conducted, and accordingly, numerous microbial genomes have been decoded. In particular, genomic studies of actinomycetes, micro-organisms that readily produce natural products, led to the discovery of biosynthetic gene clusters responsible for producing natural products. New explorations for natural products through a comprehensive approach combining genomic information with conventional methods show great promise for the discovery of new natural products and even systematic generation of unnaturally occurring compounds.     

解析2009年度诺贝尔生理学或医学奖——端粒与端粒酶

美国加州大学旧金山分校的伊丽莎白·布莱克本（Elizabeth H. Blackburn）、约翰·霍普金斯医学院的卡罗尔·格雷德（Carol W. Greider）和马萨诸塞州总医院的杰克·绍斯塔克（Jack W. Szostak）,因为“发现端粒和端粒酶如何保护染色体”,而获得2009年度诺贝尔奖生理学或医学奖。这个结果已在很多人的意料之中。因为端粒和端粒酶的发现揭示了线性染色体末端复制的机制,以及端粒和端粒酶在保护染色体及维持遗传稳定性中的中心作用。端粒和端粒酶的发现为科学家认识并探索衰老和肿瘤的发生机制开辟了新领域,对预防和治疗衰老及与衰老相关的疾病（如肿瘤）具有重要科学和应用意义。     

细胞内一种耗能蛋白质降解途径的发现——2004年诺贝尔化学奖工作介绍

2004年诺贝尔化学奖授予Aaron Ciechanover,Avram Hershko和Irwin Rose三位科学家,以表彰他们在上世纪80年代发现了泛素介导的蛋白质降解过程。文章简单介绍了该现象的科学发现历程,并讨论了该科学发现历程给予我们的启示。     

触觉受体NOMPC及听觉受体TMC的发现

人类感觉包括：视觉、听觉、嗅觉、味觉、触觉,还有温觉、痛觉等. 生物体是如何感知物理世界的问题一直吸引着人类,虽然在不同感知觉受体的发现及研究过程中不断取得新的突破性进展,但是对这些感知觉基础生物学层面的理解仍然有限. 2021年度诺贝尔生理学或医学奖授予感知觉研究领域,以表彰David Julius和Ardem Patapoutian 在感知温度与触觉受体的发现上做出的深远而广泛的贡献. 对于听觉研究而言,虽然早在1961年就获得诺贝尔奖,但是听觉受体的研究仍然不足. 本文着重对无脊椎动物触觉及听觉受体NOMPC、哺乳动物听觉受体TMC的发现及研究进程进行详细介绍,并对未来感知觉领域的发展提供建议.     

Phenotypic screening meets natural products in drug discovery†

The Nobel Prize in Physiology or Medicine 2015 was awarded for discoveries related to the control of parasitic diseases using natural products of microbial and plant origin. In current drug discovery programs, synthesized compounds are widely used as a screening source; however, this award reminds us of the importance of natural products. Here, we introduce our phenotypic screening methods based on changes in cell morphology and discuss their effectiveness and impact for natural products in drug discovery.     

1／4世纪的艾滋病毒研究——艾滋病毒的发现获得2008年诺贝尔生理学或医学奖

法国科学家弗朗索瓦丝·巴尔·西诺西和吕克·蒙塔尼因发现艾滋病毒而获得2008年诺贝尔生理学或医学奖。本文简述了艾滋病毒的发现及25年来在HIV起源、致病、治疗和预防领域取得的研究进展。     

机体的免疫反应是如何被激活的？——2011年诺贝尔生理学或医学奖解读

2011年10月3日,举世瞩目的 2011年诺贝尔生理学或医学奖在瑞典卡罗林斯卡医学院揭晓[1].因在免疫学领域取得杰出成就,美国科学家布鲁斯.博伊特勒(Bruce A.Beutler)、法国科学家朱尔斯.霍夫曼(Jules A.Hoffmann)和加拿大科学家拉尔夫.斯坦曼(Ralph M.Steinman),共同分享了这一     

Diffusive insights: on the disagreement of Christian Bohr and August Krogh at the Centennial of the Seven Little Devils

The year 2010 is the centennial of the publication of the "Seven Little Devils" in the predecessor of Acta Physiologica. In these seven papers, August and Marie Krogh sought to refute Christian Bohr's theory that oxygen diffusion from the lungs to the circulation is not entirely passive but rather facilitated by a specific cellular activity substitute to secretion. The subjects of the present reevaluation of this controversy are Christian Bohr, Professor and Doctor of Medicine (1855-1911), nominated three times for the Nobel Prize; August Krogh, Doctor of Philosophy (1874-1949), Christian Bohr's assistant and later Nobel Prize laureate (1920); and Marie Krogh, née J?rgensen, Doctor of Medicine and wife of August Krogh (1874-1943). The controversy concerned is the transport of oxygen from the lungs into the bloodstream: are passive transport and diffusion capacity together sufficient to secure the oxygen supply in all circumstances or is there an additional specific ("energy consuming" or "active") mechanism responsible for the transport of oxygen from the alveoli into the bloodstream? The present discussion purports to show that the contestants' views were closer than the parties themselves and posterity recognized. Posterity has judged the dispute unilaterally from the Nobel laureate's point of view, but it is evident that August Krogh's Nobel Prize was awarded for the discovery of a cellular activity (Christian Bohr's expression), represented by Krogh's discovery of capillary recruitment. Christian Bohr appears to have been correct in the narrower sense that the diffusion capacity at rest is not great enough to explain the transport during work; a special mechanism intervenes and optimizes the conditions under which diffusion acts. August Krogh, of course, was right in the wider sense that the transport mechanism itself is always entirely passive.     

Antiparasitic antibiotics from Japan

Antibiotics are microbial secondary metabolites and they are important for the treatment of infectious diseases. Japanese researchers have made a large contribution to studies of antibiotics, and they have also been important in the discovery of antiparasitic antibiotics. Satoshi Ōmura received the Nobel Prize in 2015 for the “discoveries concerning a novel therapy against infections caused by roundworm parasites”, which means discovery of a new nematocidal antibiotic, avermectin. Here, I review the many antiparasitic antibiotics and their lead compounds that have been discovered for use in human and veterinary medicine.     

CRISPR–Cas9: A History of Its Discovery and Ethical Considerations of Its Use in Genome Editing

Biochemistry (Moscow) - The development of a method for genome editing based on CRISPR–Cas9 technology was awarded The Nobel Prize in Chemistry in 2020, less than a decade after the discovery...     

The ubiquitin-proteasome system

The 2004 Nobel Prize in chemistry for the discovery of protein ubiquitination has led to the recognition of cellular proteolysis as a central area of research in biology. Eukaryotic proteins targeted for degradation by this pathway are first ‘tagged’ by multimers of a protein known as ubiquitin and are later proteolyzed by a giant enzyme known as the proteasome. This article recounts the key observations that led to the discovery of ubiquitin-proteasome system (UPS). In addition, different aspects of proteasome biology are highlighted. Finally, some key roles of the UPS in different areas of biology and the use of inhibitors of this pathway as possible drug targets are discussed.     

Gene silencing by double-stranded RNA

Thanks to the Nobel Foundation for permission to publish this Lecture. We report here the Nobel Lecture delivered by Professor Andrew Z Fire. Together with the accompanying lecture by Professor Mello this lecture describes the exciting years leading to the discovery of RNA interference (RNAi) and some of the underlying molecular mechanisms. Professor Fire nicely points out his own contribution and the contribution of other research groups to the development of this field. He also presents an interesting discussion on the role of RNAi in immunity and challenges us with a number of open questions. The lecture ends presenting the great potential of exploiting RNAi for therapeutical purposes.     

The quest for industrial enzymes from microorganisms†

Satoshi ōmura, Professor Emeritus at Kitasato University, was awarded the Nobel Prize for his discovery of a substance of tremendous value to mankind from a microorganism. As a researcher who regularly deals with enzymes produced by microorganisms and a person engaged in microorganism-based business, Professor ōmura’s Nobel Prize fills me with great pride and joy. It is perhaps not surprising that this Nobel Prize-winning research would emerge from Asia, specifically Japan, where people live in harmony with nature rather than try to conquer it. At Amano Enzyme Inc., we devote ourselves to searching for novel enzymes from microorganisms. While incorporating my own experiences, I will recount the stories of a few discoveries of valuable enzyme-producing microbes in soil and bacterial strain libraries. I will also briefly introduce microbial strain library construction as a tool for facilitating the identification of the desired producing bacteria.     

RNA interference: unraveling a mystery

Andrew Fire and Craig Mello have won the Nobel Prize in Medicine or Physiology for their discovery of RNA interference. Mary K. Montgomery, then a postdoc in the Fire laboratory, participated in some of the key experiments.     

Streptomycin: discovery and resultant controversy

The antibiotic streptomycin was discovered soon after penicillin was introduced into medicine. Selman Waksman, who was awarded the Nobel Prize for the discovery, has since generally been credited as streptomycin's sole discoverer. However, one of Waksman's graduate students, Albert Schatz, was legally recognized as streptomycin's co-discoverer and received a share of the royalties from the drug. The aim of this essay is to discuss the streptomycin story, largely using previously unquoted archival material, and in particular to provide further evidence for the important role which Schatz played in the discovery.     

The history of inhibitors of angiotensin converting enzyme.

This review paper by Sir John Vane, The Nobel Prize Laureate for the first time reveals the insides of discovery of inhibitors of angiotensin converting enzyme (ACE-1), presently known as important drugs for the treatment of hypertension, congestive heart failure and coronary artery disease.     

Genome editing of human pluripotent stem cells to generate human cellular disease models

Disease modeling with human pluripotent stem cells has come into the public spotlight with the awarding of the Nobel Prize in Physiology or Medicine for 2012 to Drs John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. This discovery has opened the door for the generation of pluripotent stem cells from individuals with disease and the differentiation of these cells into somatic cell types for the study of disease pathophysiology. The emergence of genome-editing technology over the past few years has made it feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Here, recent technological advances in genome editing, and its utility in human biology and disease studies, are reviewed.