The 2009 Lindau Nobel Laureate Meeting: Martin Chalfie,Chemistry 2008

American Biologist Martin Chalfie shared the 2008 Nobel Prize in Chemistry with Roger Tsien and Osamu Shimomura for their discovery and development of the Green Fluorescent Protein (GFP).Martin Chalfie was born in Chicago in 1947 and grew up in Skokie Illinois. Although he had an interest in science from a young age-- learning the names of the planets and reading books about dinosaurs-- his journey to a career in biological science was circuitous. In high school, Chalfie enjoyed his AP Chemistry course, but his other science courses did not make much of an impression on him, and he began his undergraduate studies at Harvard uncertain of what he wanted to study. Eventually he did choose to major in Biochemistry, and during the summer between his sophomore and junior years, he joined Klaus Weber''s lab and began his first real research project, studying the active site of the enzyme aspartate transcarbamylase. Unfortunately, none of the experiments he performed in Weber''s lab worked, and Chalfie came to the conclusion that research was not for him.Following graduation in 1969, he was hired as a teacher Hamden Hall Country Day School in Connecticut where he taught high school chemistry, algebra, and social sciences for 2 years. After his first year of teaching, he decided to give research another try. He took a summer job in Jose Zadunaisky''s lab at Yale, studying chloride transport in the frog retina. Chalfie enjoyed this experience a great deal, and having gained confidence in his own scientific abilities, he applied to graduate school at Harvard, where he joined the Physiology department in 1972 and studied norepinephrine synthesis and secretion under Bob Pearlman. His interest in working on C. elegans led him to post doc with Sydney Brenner, at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England. In 1982 he was offered position at Columbia University.When Chalfie first heard about GFP at a research seminar given by Paul Brehm in 1989, his lab was studying genes involved in the development and function of touch-sensitive cells in C. elegans. He immediately became very excited about the idea of expressing the fluorescent protein in the nematode, hoping to figure out where the genes were expressed in the live organism. At the time, all methods of examining localization, such as antibody staining or in situ hybridization, required fixation of the tissue or cells, revealing the location of proteins only at fixed points in time.In September 1992, after obtaining GFP DNA from Douglas Prasher, Chalfie asked his rotation student, Ghia Euskirchen to express GFP in E. coli, unaware that several other labs were also trying to express the protein, without success. Chalfie and Euskirchen used PCR to amplify only the coding sequence of GFP, which they placed in an expression vector and expressed in E.coli. Because of her engineering background, Euskirchen knew that the microscope in the Chalfie lab was not good enough to use for this type of experiment, so she captured images of green bacteria using the microscope from her former engineering lab. This work demonstrated that GFP fluorescence requires no component other than GFP itself. In fact, the difficulty that other labs had encountered stemmed from their use of restriction enzyme digestions for subcloning, which brought along an extra sequence that prevented GFP''s fluorescent expression. Following Euskirchen''s successful expression in E. coli, Chalfie''s technician Yuan Tu went on to express GFP in C. elegans, and Chalfie published the findings in Science in 1994.Through the study of C. elegans and GFP, Chalfie feels there is an important lesson to be learned about the importance basic research. Though there has been a recent push for clinically-relevant or patent-producing (translational) research, Chalfie warns that taking this approach alone is a mistake, given how "woefully little" we know about biology. He points out the vast expanse of the unknowns in biology, noting that important discoveries such as GFP are very frequently made through basic research using a diverse set of model organisms. Indeed, the study of GFP bioluminescence did not originally have a direct application to human health. Our understanding of it, however, has led to a wide array of clinically-relevant discoveries and developments. Chalfie believes we should not limit ourselves: "We should be a little freer and investigate things in different directions, and be a little bit awed by what we''re going to find."Download video file.^{(152M, mp4)}     

The 2009 Lindau Nobel Laureate Meeting: Sir Harold Kroto,Chemistry 1996

English Chemist Harold Kroto shared the 1996 Nobel Prize in Chemistry with Robert Curl and Richard Smalley for their discovery of Fullerenes (C₆₀), molecules composed completely of carbon (C₆₀) that form hollow spheres (also known as Buckyballs), tubes, or ellipsoids. These structures hold the potential for use in future technologies ranging from drug development and antimicrobial agents, to armor and superconductors.Harold Kroto was born in Wisbech, Cambridgeshire in 1939 and grew up in Bolton. Educated at Bolton School, he entered Sheffield University in 1958 to study Chemistry. During his time there he played tennis for the university team, illustrated the university''s magazine covers, and played folk music with other students. Enjoying his time at Sheffield very much, he chose to stay on and complete a Ph.D. in Chemistry under Richard Dixon.Following graduation in 1964, Kroto went on to post doc at the National Research Council (NRC) in Ottowa, Canada where microwave spectroscopy became his specialty. After two years of study at the NRC he spent a year at Bell Laboratories. He then accepted a position as a tutorial fellow at the University of Sussex, where he was soon offered a permanent position. There, he applied his expertise in microwave spectroscopy to the field of astronomy and spent several fruitful years detecting long carbon chains in the interstellar medium.Upon hearing of the work of Richard Smalley at Rice, who developed a laser that could vaporize graphite, Kroto thought they could use Smalley''s instrument to see carbon chains similar to those they had observed in interstellar matter. He suggested his idea for an experiment to Bob Curl, also at Rice. In 1985 he traveled to Rice to perform the experiment (and also to visit a half-price bookstore he''d heard about in Houston).Although he felt certain that the apparatus would create the carbon chains, the experiment revealed a totally unexpected result: the spontaneous formation of spherical shapes, which they called Buckminster Fullerenes in honor of the architect who popularized the geodesic dome.Though he is pleased to have received the Nobel Prize, Kroto does not believe in prizes or competition as a motivator for scientific (or athletic) progress. Rather, he believes that the pursuit of science or athletics should be simply for the enjoyment or interest in the subject matter, and he prefers to investigate subjects that other people aren''t working on.Kroto has mixed feelings about the effect the prize has had on his life. On the one hand, he would like to be able to spend more time pursuing graphic design, something he has always deeply enjoyed. On the other hand, he now enjoys a sense of responsibility for supporting the scientific community.As an atheist, Kroto feels that science is, in itself, atheistic. He doesn''t accept anything without evidence. Kroto expresses concern about people holding positions of power who do not use evidence as a basis for decision-making. "When they are prepared to accept one of 20-30 stories from thousands of years ago, I wonder what else they are prepared to accept when it comes to decisions which affect me?"Kroto is particularly worried about the effect of policies that require the teaching of non-scientific ideas, to the detriment of evidence-based scientific education. He points to the forced teaching of creationism in public schools and the existence of a "creation museum" in the United States as sources of misinformation that have given rise to "a whole generation of school children who''ve been abused."Download video file.^{(80M, mp4)}     

The 2009 Lindau Nobel Laureate Meeting: Roger Y. Tsien,Chemistry 2008

American biochemist Roger Tsien shared the 2008 Nobel Prize in Chemistry with Martin Chalfie and Osamu Shimomura for their discovery and development of the Green Fluorescent Protein (GFP). Tsien, who was born in New York in 1952 and grew up in Livingston New Jersey, began to experiment in the basement of the family home at a young age. From growing silica gardens of colorful crystallized metal salts to attempting to synthesize aspirin, these early experiments fueled what would become Tsien''s lifelong interest in chemistry and colors.Tsien''s first official laboratory experience was an NSF-supported summer research program in which he used infrared spectroscopy to examine how metals bind to thiocyanate, for which he was awarded a $10,000 scholarship in the Westinghouse Science Talent Search. Following graduation from Harvard in 1972, Tsien attended Cambridge University in England under a Marshall Scholarship. There he learned organic chemistry --a subject he''d hated as an undergraduate-- and looked for a way to synthesize dyes for imaging neuronal activity, generating BAPTA based optical calcium indicator dyes.Following the completion of his postdoctoral training at Cambridge in 1982, Tsien accepted a faculty position at the University of California, Berkeley. There he and colleagues developed and improved numerous small molecule indicators, including indicators fura-2 and indo-1.In 1989, Tsien moved his laboratory to the University of California at San Diego, where he and his colleagues developed the enhanced mutant of GFP as a way to devise a cyclic AMP (cAMP) sensor for use in live cells. They initially engineered molecules to take advantage of the conformational change that occurs when cAMP binds to protein kinase A (PKA). By labeling one part of PKA with fluoroscein and another with a rhodamine, they hoped to detect Fluorescence Resonance Energy Transfer (FRET), which would occur when the two molecules were in close proximity. The initial experiments presented numerous difficulties due to the challenges of expressing PKA subunits in E. coli, labeling the protein without destroying its function, and delivering the protein to cells via microinjection.Eventually, Tsien sought a more elegant approach, hoping to use and modify a naturally fluorescent protein that could be expressed in the cell. GFP originally described by Davenport in 1955, extracted and purified by Shimomura in 1965, and cloned by Prasher in 1992 was an appealing candidate. To make the protein more useful for their FRET studies, Tsien and colleagues modified the amino acid structure of the protein (S65T). The improved protein had an excitation peak near that of fluoroscein, and was photostable. Tsien and colleagues also solved the protein''s crystal structure, enabling them to generate additional colors with spectral properties suitable for FRET. However, when they attempted to use the GFP proteins in the detection of cAMP, they experienced further difficulties with PKA. Instead, their first successful use of GFP derivatives for FRET was in the detection of intracellular calcium using their engineered calmodulin-based calcium indicator, Cameleon.In a short time, Tsien''s work has led to further technological developments and important scientific findings. GFP and its derivatives have been used in a wide range of biological applications, from the study of protein localization to understanding how HIV spreads from cell to cell. The need for such probes is highlighted by the abundance of research conducted using these fluorescent proteins, as well as the continued development of similar fluorescent proteins, such as the coral-derived dsRED.Tsien is currently developing genetically encoded Infrared Fluorescent Proteins (IFPs), which with their long emission wavelengths of >700 nm, have the ability to pass through living tissue and improve imaging in living organisms. He is also building synthetic molecules for use in humans. He cites team effort and the contributions of students and post-docs as key components of progress and success: "Even if I had the time, I couldn''t have done the experiments, because I don''t know how. It''s very much a team effort."Download video file.^{(144M, mp4)}     

The 2009 Lindau Nobel Laureate Meeting: Werner Arber,Physiology or Medicine 1978

Swiss microbial geneticist, Werner Arber shared the 1978 Nobel Prize in Physiology or Medicine with Hamilton Smith and Daniel Nathans for their discovery of restriction endonucleases.Werner Arber was born in Granichen, Switzerland in 1929. Following a public school education, he entered the Swiss Polytechnical School in Zurich in 1949, working toward a diploma in natural sciences. There, his first research experience involved isolating and characterizing an isomer of chlorine. Following graduation in 1953, Arber joined a graduate program at the University of Geneva, taking on an assistanceship in electron microscopy (EM), in which he studied gene transfer in the bacterial virus (bacteriophage) lambda. Eventually encountering limitations with EM as a tool, he began using microbial genetics as a methodology for his studies. The study of microbial genetics had been possible for a relatively short time: DNA had been discovered to carry genetic information only a decade before he d entered the field.After earning his Ph.D. in 1958, Arber continued to develop skills in microbial genetics, working with colleagues in the United States for a short time before returning to Geneva at beginning of 1960. There, he continued working on lambda transduction in E. coli, but found that the virus would not efficiently propagate. Recalling research done seven years earlier by Joe Bertani and Jean Weigle on "host-controlled restriction-modification", he realized there must be a host-controlled modification of the invading DNA, and sought to identify the mechanism. Based on Grete Kallengerger s work that demonstrated degradation of both irradiated and non-irradiated phage lambda following injection in a host, Arber and his graduate student, Daisy Dussoix further investigated the fate of DNA, and found that restriction and modification (later determined to be postreplicative nuclotide methylation) directly affected DNA, but did not cause mutations. They also found that theses were properties of the bacterial strains, and that both viral and cellular DNA were degraded. Together, Arber and Dussoix reported their findings to scientific community in 1961 at the First International Biophysics Congress in Stockholm. Aber also presented the research to the Science Faculty of University of Geneva in 1962, earning the Plantamour-Prevost prize. Based on his work and the work of others, he hypothesized that an enzyme in the host bacterium cut DNA into smaller pieces at specific sites, and methylase modified the host DNA to protect it from the digestive enzyme. These theories were later confirmed by Urs Kuhnlein, who found that mutation of specific sites rendered the phage resistant to cleavage; Hamilton smith, who identified Type II endonuclease HindII; and Daniel Nathans, who used HindII to break the SV40 virus into 11 fragments, allowing him to determine its method of replication.Since the discovery of restriction endonucleases, researchers have used them as tools to study the functions of genes of all types of organisms. Restriction enzymes have also facilitated the study of gene functions and enabled production of substances of medical and nutritional importance. Arber feels that in the next few decades we will learn much from the study of epigentics --factors that can affect the phenotype of an organism without changing the genetic information--. He is proud that, in that studying restriction degradation and DNA methylation in the 1960s, he was among the first in studying epigenetic phenomenon.Download video file.^{(118M, mp4)}     

生命科学研究的又一个里程碑——记2003年度诺贝尔化学奖

瑞典皇家科学院宣布 ,美国的两位科学家Agre和MacKinnon ,因他们在细胞膜物质转运通道蛋白质研究方面的重要发现分享 2 0 0 3年度诺贝尔化学奖 .Agre发现了水通道 (waterchannel) ,并且解释了水通道对水分子的选择性通透等重要特性 ;MacKinnon确立了K 离子通道的高分辨率的三维结构 ,并且详细地阐明了其离子选择性等功能机制 .两位科学家把他们对科学研究前沿领域的高度敏感性与科学的方法论紧密结合在一起 .他们从化学基础研究出发 ,为生命科学前沿领域后基因组的研究作出了卓越贡献     

Endogenous DNA Damage and Repair Enzymes—A short summary of the scientific achievements of Tomas Lindahl,Nobel Laureate in Chemistry 2015

Tomas Lindahl completed his medical studies at Karolinska Institute in 1970. Yet, his work has always been dedicated to unraveling fundamental mechanisms of DNA decay and DNA repair. His research is characterized with groundbreaking discoveries on the instability of our genome, the identification of novel DNA repair activities, the characterization of DNA repair pathways, and the association to diseases, throughout his 40 years of scientific career.     

The 2009 Nobel Prize in Chemistry: Thomas A. Steitz and the structure of the ribosome

Over the past 200 years, there have been countless groundbreaking discoveries in biology and medicine at Yale University. However, one particularly noteworthy discovery with profoundly important and broad consequences happened here in just the past two decades. In 2009, Thomas Steitz, the Sterling Professor of Molecular Biophysics & Biochemistry, was awarded the Nobel Prize in Chemistry for "studies of the structure and function of the ribosome," along with Venkatraman Ramakrishnan of the MRC Laboratory of Molecular Biology and Ada E. Yonath of the Weizmann Institute of Science. This article covers the historical context of Steitz's important discovery, the techniques his laboratory used to study the ribosome, and the impact that this research has had, and will have, on the future of biological and medical research.     

开创手性催化反应研究的新领域——2001年诺贝尔化学奖评介

1 .三位美日科学家摘桂瑞典皇家科学院在 2 0 0 1年 1 0月 1 0日宣布 ,将 2 0 0 1年度诺贝尔化学奖授予不对称催化合成的 3位先驱化学家 :美国孟山都生物技术公司 (Ｍｏｎｓａｎｔｏ)的威廉·Ｓ·诺尔斯(ＷｉｌｌｉａｍＳ .Ｋｎｏｗｌｅｓ)博士 ,美国ＴｈｅＳｃｒｉｐｐｓ研究所 (ＴＳＲＩ)的Ｋ·巴里·夏普莱斯 (Ｋ .ＢａｒｒｙＳｈａｒｐｌｅｓｓ)教授 ,日本名古屋大学的野伊良治(ＲｙｏｊｉＮｏｙｏｒｉ)教授 ,以表彰他们在手性催化氢化反应和手性催化氧化反应研究领域所作出的重大贡献。新世纪的第一个诺贝尔化学奖获奖成果虽然是非常基…     

核糖体的结构与功能研究——2009年诺贝尔化学奖简介

一系列高分辨率的核糖体及其30 S、50 S亚基的晶体结构揭示了这个极其复杂的蛋白质翻译机器的重要作用机理,对在分子水平上了解生命机体产生和形成的一个基本环节(蛋白质合成)具有重大意义,同时为新型抗生素的设计与研发开辟了新方向新途径,对人类健康与生命保障具有重要作用．