Laboratory of Molecular Biology

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The Laboratory of Molecular Biology (also LMB ) is a research facility in Cambridge , England , whose scientists were instrumental in the molecular biology revolution in the 1950s and 1960s. Since around 1960 it has been a medical research institute with many different focuses.

The beginnings: 1947 - 1961

After studying organic chemistry , Max Perutz left his home country Austria in 1936 , went to the University of Cambridge as a post-graduate and joined the X-ray crystallography group led by JD Bernal . At the Cavendish Laboratory he began his studies on hemoglobin , which was to accompany him throughout his life. After the death of Lord Rutherford , his successor Lawrence Bragg , a pioneer of X-ray crystallography, became the new Cavendish Professor of Physics in 1938 . During this time, Bragg provided sustained support to Perutz's work. After the Second World War , many physicists turned to biology and brought with them new methods and ways of thinking. John Kendrew joined Perutz's research group in order to study a protein related to hemoglobin, myoglobin , from 1946 onwards . In the following year the working group was founded at the Medical Research Council (MRC) under the direction of Harold Percival Himsworth , the “MRC Unit for the Study of the Molecular Structure of Biological Systems”, which addressed the questions of structural biology. This group was joined by Hugh Huxley in 1948 to work on muscle proteins. From 1949 Francis Crick worked on the X-ray crystallography of proteins. In 1951, James Watson came to the MRC. 1953 became the annus mirabilis of biology. Watson and Crick discovered the double helix structure of DNA. This made it clear that biological information is stored as a linear code and doubled during cell division . Perutz discovered that the three-dimensional structure of large proteins such as those of myoglobin and hemoglobin can in principle be derived from X-ray spectroscopic data by marking groups of molecules with heavy atoms. Huxley developed the filament slip theory . In 1957 the working group was renamed and has since been called “MRC Unit for Molecular Biology”. In the same year, Sydney Brenner joined the group and Vernon Ingram discovered that sickle cell anemia is caused by an amino acid replacement in the hemoglobin molecule. In 1958, Crick's essay On Protein Synthesis appeared , in which the central dogma of molecular biology , the sequence hypothesis and the adapter theory were formulated. In 1961, Brenner was involved in the discovery of messenger RNA . In the same year he and Crick developed the assumption that the genetic code is read in triplets. All of this work was done in a simple building called “The Hut”.

Opening of the LMB in 1962

The LMB building. In the foreground you can see the lecture room.

The MRC built a new laboratory building outside Cambridge, the LMB, to which the Cavendish Structural Biology group moved in 1962. They were joined by Fred Sanger’s working group, which was previously based in the Biochemistry Department, and Aaron Klug , who came from London. Sanger had received the Nobel Prize in Chemistry in 1958 for his work on the sequencing of proteins (especially insulin ) . The new laboratory was opened by Queen Elizabeth II in 1962. A little later, Kendrew and Perutz received the Nobel Prize in chemistry and Crick and Watson for medicine. Perutz headed the laboratory with its three departments: structural biology (Kendrew); Molecular Genetics (Crick); Protein chemistry (Sanger). A total of around 40 scientists worked there. However, their number increased rapidly as many post-docs came to Cambridge from the USA.

Molecular Biology: 1962 and after

In the following decade, knowledge in the field of molecular biology grew rapidly. The three-dimensional structure of a number of important proteins, including myoglobin and hemoglobin, were elucidated . The structure of chymotrypsin was researched by David Blow . The principle of the genetic code was elucidated by Crick on the basis of numerous indications from researchers from around the world. First the start and stop signals for the messenger RNA were discovered . Then in 1966 Crick proposed the wobble hypothesis , which states that the genetic code has degenerated. This explains that the number of tRNA molecules responsible for reading the code is smaller than the number of computationally possible codons. Sanger developed new methods for sequencing RNA and DNA , for which he received his second Nobel Prize in Chemistry in 1980. Later on, John Sulston was significantly involved in the sequencing of entire genomes . John Derek Smith and Sid Altman investigated the question of how a t-RNA precursor becomes a mature t-RNA molecule. This later led to the discovery of ribozymes . Aaron Klug clarified the structure of tRNAs, discovered the zinc fingers and received the Nobel Prize in Chemistry in 1982. The structure of ATP synthase was elucidated by John E. Walker and Andrew Leslie. Walker received the 1997 Nobel Prize in Chemistry for this . Venkatraman Ramakrishnan received the 2009 Nobel Prize in Chemistry for elucidating the ribosome structure .

Differentiation of the focus of work

At the end of the 1960s it became clear that some problems in biology can be solved with the resources of molecular biology.

Developmental Biology C. elegans

Sydney Brenner began his work with the C. elegans worm in 1965. His group soon grew to include the scientists who continue to form the core of C. elegans research today. Sulston described the development of each individual cell in the small worm and John White the entire network of its nervous system. Robert Horvitz , who helped with the work, received the Nobel Prize for Medicine in 2002 together with Brenner and Sulston. Jonathan Hodgkin described the genetic mechanisms of sex development in C. elegans and John Gurdon used frog eggs as a system for translating foreign mRNA. Peter Lawrence began his work on pattern formation and helped to describe the compartments that determine the body plan in Drosophila. He convinced Crick to be interested in the questions of morphogenetic gradients that contribute to pattern formation.

immunology

César Milstein has worked on the problems of antibody diversity for many years. Together with Georges JF Köhler he developed a method for the production of monoclonal antibodies . For this they both received the Nobel Prize for Medicine in 1984. Greg Winter pioneered the development of antibody engineering. He found out how to make and use new antibodies and antibody fragments. They are indispensable in medicine today. A work by Leo James in 2010 showed that viral infections can be combated not only by destroying infected cells, but also by means of mechanisms within the cell using the TRIM21 protein. This opens up new possibilities for combating viral infections.

Cell biology

Because classical molecular biology turned from clarifying the structure of individual molecules to the problems of cell biology and development, the department for molecular genetics was renamed to one for cell biology. Mark Bretscher discovered how the proteins in the human erythrocyte membrane are arranged by phospholipid translocators . Richard Henderson and Nigel Unwin developed the method of electron crystallography to elucidate the structure of bacteriorhodopsin . Barbara Pearse discovered the main components of the clathrin involved in endocytosis . Mark Bretscher, Hugh Pelham and Sean Munro investigated how proteins are positioned in certain areas of the cell. John Kilmartin examined the structure and function of the spindle pole bodies . In yeast, these are suspension points for the chromosomes during cell division. Chromosomes have long been the focus of interest in the LMB. These investigations were initiated by Roger Kornberg . He discovered one of the basic formations of DNA condensation in the nucleosome and continued to work on the question of how DNA is folded in the cell.

Neurobiology

A new department for neurobiology was established in 1993. The further development of electron crystallography by Unwin helped to elucidate the structure of the acetylcholine receptors . Michel Goedert has identified various proteins that are associated with Alzheimer's disease .

Measuring instruments and scientific equipment

Scientific progress is not infrequently based on technical innovations. The LMB was often a leader in this area, for example in the sequencing of proteins and DNA, the production of monoclonal antibodies, the development of X-ray structure analysis and confocal microscopy.

Well-known alumni

Permanent employees of the LMB who received a Nobel Prize:

Temporary employees of the LMB who received a Nobel Prize:

Administrative structure

The LMB's early success was also fueled by a simple administrative structure. The MRC largely gave the scientists a free hand in how they regulate their affairs. It was important to Perutz that the work of the scientists in all areas was made easier. There was only one budget, which made running the laboratory cheaper. All consumables can easily be obtained from a common supply against a signature. Michael Fuller was responsible for the smooth functioning. There was no formal hierarchy, which significantly improved collaboration. Today there are 400 scientists at the LMB, including 130 post-docs and 90 students.

literature

  • John Finch: A Nobel Fellow On Every Floor . Medical Research Council, 2008, ISBN 978-1-84046-940-0 , 381 pages; this book is all about the MRC Laboratory of Molecular Biology, Cambridge.

Web links

Commons : Laboratory of Molecular Biology  - collection of images, videos and audio files

Individual evidence

  1. ↑ Francis H. Crick: On protein synthesis . In: Symp Soc Exp Biol. , 1958, 12, pp. 138-163 , PMID 13580867 .
  2. ↑ a b c d e John Finch: A Nobel Fellow On Every Floor . In: Medical Research Council , 2008, ISBN 978-1-84046-940-0 , 381 pp.
  3. ^ The Nobel Prize in Chemistry 2009 .
  4. ↑ A cure for the common cold may finally be achieved as a result of a . November 2, 2010.