Laboratory of Molecular Biology
Encyclopedia
The Laboratory of Molecular Biology (or LMB) is a research institute in Cambridge
, England
, which was at the forefront of the revolution in molecular biology
which occurred in the 1950–60s, since then it remains a major medical research laboratory with a much broader focus.
, following an undergraduate training in organic chemistry, left Austria
in 1936 and came to the University of Cambridge
to study for a PhD, joining the X-ray crystallographic group
led by J.D. Bernal. Here, in the Cavendish laboratory
, he started his life-long work on hemoglobin
. The death of Lord Rutherford
led to his successor, Lawrence Bragg, a pioneer in X-Ray crystallography, becoming the new Cavendish professor of physics in 1938. Bragg became a major supporter of Perutz and his group in those early days.
After World War II
, many scientists from the physical side of science turned to biology, bringing with them a new way of thinking and expertise. John Kendrew
joined Perutz’s group to study a protein closely related to hemoglobin — myoglobin
— in 1946. In 1947, the Medical Research Council
(MRC), under the guidance of its Secretary Harold Himsworth, decided to form and support the “MRC Unit for the Study of the Molecular Structure of Biological Systems”. The group, which by 1948 also included Hugh Huxley
working on muscle, was joined in 1949 by Francis Crick
, who worked initially on protein crystallography. In 1951 they were joined by James Watson
.
1953 was an annus mirabilis
: Watson and Crick discovered the double-helical structure of DNA
, which revealed that biological information was encoded in a linear structure and how this information could be duplicated during cell division
. Perutz discovered that the detailed three dimensional structures of proteins, such as myoglobin and hemoglobin could, in principle, be solved by X-ray analysis using a heavy metal atom labeling technique. Hugh Huxley discovered that muscle
contraction works by a sliding filament mechanism
.
In 1957 the group’s name was changed to the “MRC Unit for Molecular Biology”. Also that year, Vernon Ingram
discovered that the disease sickle cell anaemia is caused by a single amino acid change in the hemoglobin molecule and Sydney Brenner
joined the Unit. In 1958, Crick’s review “On Protein Synthesis” appeared: this laid out, for the first time, the central dogma of molecular biology
, the sequence hypothesis
and the adaptor hypothesis
. In 1961 Brenner helped discover messenger RNA
and, in the same year, he and Crick established that the genetic code
was read in triplets.
All this work was accomplished in a single-storey temporary building (The Hut), a few rooms in the Austin Wing, a room with a lean-to glass front (The Greenhouse) and a short sealed off corridor (The Gallery) within the Cavendish laboratory.
from London. Sanger had invented methods for determining the sequence of amino acids in a protein: he was awarded the Nobel prize
for chemistry in 1958 for the first protein sequence, that of insulin
. The new laboratory was opened by Queen Elizabeth II
in 1962. Later that year, Kendrew and Perutz shared the Nobel prize for chemistry and Crick and Watson received a share of the Nobel prize for physiology or medicine.
The new LMB had Perutz as its chairman and contained 3 divisions: Structural Studies, headed by Kendrew; Molecular Genetics (Crick); Protein Chemistry (Sanger). In all, there were about 40 scientists but this number rapidly increased, particularly with a large influx of post-doctoral visitors from the US.
, hemoglobin
and chymotrypsin
, the last by David Blow. The genetic code, from evidence around the world, was assembled by Crick. Punctuation signals in the messenger RNA
— where to start translating the RNA into a protein sequence, and where to stop — were discovered. Crick suggested how the tRNA molecules — his original adaptors — read the messenger in his wobble hypothesis
. Sanger devised new methods for sequencing RNA
molecules and then later for DNA molecules (for which he received a second Nobel prize in chemistry in 1980). Much later, this line was extended to include determining the sequence of whole genomes, in which John Sulston played a key role. How tRNA precursor molecules are processed to give a functional tRNA was elucidated by John Smith
and Sid Altman, and this later led to the discovery of ribozymes. The atomic structure of the first tRNA molecule was solved and zinc fingers discovered by Klug (who received the Nobel prize for chemistry in 1982). The structure of the ATP synthase
was solved by John Walker
and Andrew Leslie, for which Walker shared the Nobel prize for chemistry in 1997. The structure of the ribosome
was solved by Venkatraman Ramakrishnan, for which he shared the Nobel prize for chemistry in 2009.
the entire wiring diagram of its nervous system. Robert Horvitz, who helped in the cell lineage, was to share the Nobel prize for physiology or medicine with Brenner and Sulston in 2002. Jonathan Hodgkin established the genetic pathway in C.elegans which controls sex determination. John Gurdon
developed the use of the frog oocyte to translate mRNAs.
Peter Lawrence
came to study pattern formation, helping discover how compartments in Drosophila determine the fly’s body plan. Under his influence, Crick also became interested in morphogenetic gradients and how they may help specify biological patterns.
had over many years been working on antibody variation. He was joined in this by Georges Kohler and, together, they discovered how to produce monoclonal antibodies
. For this they shared the Nobel prize for physiology or medicine in 1984. This area was extended by Greg Winter
who pioneered antibody engineering to make novel human antibodies and antibody fragments. Both monoclonal antibodies and their fragments are now of major medical importance.
Publishing in November 2010 in the journal Proceedings of the National Academy of Sciences Leo James led a research group to discover the ability of the immune system to fight viruses inside infect cells. Standard immunology textbooks taught that once a cell is invaded the body has no alternative but to kill the cell. But the research showed how a protein called TRIM21
attacks invaders of the cell which aren't antibodies. This research paves the way for finally finding a cure to the common cold i.e. Rhinoviruses, to noravirus, which causes winter vomiting and to rotavirus, which cause gastroenteritis by utilising and boosting the natural mechanism of attacking cell invaders.
discovered the topological way proteins are arranged in the human erythrocyte membrane
and its phospholipid asymmetry
. Richard Henderson
and Nigel Unwin
developed electron crystallography
to determine the structure of two dimensional arrays, applying this to the bacterial purple protein, bacteriorhodopsin
. Barbara Pearse
discovered the major components of clathrin-coated vesicles, structures formed during endocytosis
, and a low resolution structure of the cage-like lattice around them was determined. How proteins become localised to different parts of the cell — such as to the endoplasmic reticulum
, Golgi apparatus
or the plasma membrane — and the role of this in cell polarity, have been elucidated by Bretscher, Hugh Pelham and Sean Munro. The spindle pole bodies
— the large structures in yeast cells which act as the foci to which chromosomes are moved during mitosis — have been purified and a low resolution structure of them deduced by John Kilmartin.
A continuing interest has been the structure of chromosomes. This was initiated by a visitor, Roger Kornberg, who discovered the first level of condensation of DNA, the nucleosome
, and continues with the focus on understanding the higher orders of folding DNA.
, which activates many neurons. Michel Goedert has identified variant proteins associated with Alzheimer’s disease.
Visitors who have received a Nobel prize for work done, or initiated, at the LMB include:
In addition, many alumni have gained great distinction which has been recognised by elections to learned bodies. A link to a list of past members of the LMB can be found below.
Within the LMB, Perutz’s criterion of how to arrange things was that the act of doing science should be facilitated at all levels. The LMB had a single budget: there were no personal budgets or equipment — everything was communal, which made running the lab cheaper. It had state of the art equipment and was well financed by the MRC. Chemical reagents, glassware and other expendibles could be withdrawn from an extremely well stocked store with no more than a signature. Key to the smooth functioning of the lab was Michael Fuller, who was responsible for its day-to-day running.
There was no overt hierarchy; everyone was on first-name terms. Most members of the lab met freely in the canteen, situated at the top of the building with a view across Cambridge, for mid-morning coffee, lunch and afternoon tea. This assisted inter-divisional communication and collaboration.
Today the LMB has around 340 scientists, of whom 130 are postdoctoral visitors and 90 students.
Cambridge
The city of Cambridge is a university town and the administrative centre of the county of Cambridgeshire, England. It lies in East Anglia about north of London. Cambridge is at the heart of the high-technology centre known as Silicon Fen – a play on Silicon Valley and the fens surrounding the...
, England
England
England is a country that is part of the United Kingdom. It shares land borders with Scotland to the north and Wales to the west; the Irish Sea is to the north west, the Celtic Sea to the south west, with the North Sea to the east and the English Channel to the south separating it from continental...
, which was at the forefront of the revolution in molecular biology
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
which occurred in the 1950–60s, since then it remains a major medical research laboratory with a much broader focus.
Early beginnings: 1947-61
Max PerutzMax Perutz
Max Ferdinand Perutz, OM, CH, CBE, FRS was an Austrian-born British molecular biologist, who shared the 1962 Nobel Prize for Chemistry with John Kendrew, for their studies of the structures of hemoglobin and globular proteins...
, following an undergraduate training in organic chemistry, left Austria
Austria
Austria , officially the Republic of Austria , is a landlocked country of roughly 8.4 million people in Central Europe. It is bordered by the Czech Republic and Germany to the north, Slovakia and Hungary to the east, Slovenia and Italy to the south, and Switzerland and Liechtenstein to the...
in 1936 and came to the University of Cambridge
University of Cambridge
The University of Cambridge is a public research university located in Cambridge, United Kingdom. It is the second-oldest university in both the United Kingdom and the English-speaking world , and the seventh-oldest globally...
to study for a PhD, joining the X-ray crystallographic group
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
led by J.D. Bernal. Here, in the Cavendish laboratory
Cavendish Laboratory
The Cavendish Laboratory is the Department of Physics at the University of Cambridge, and is part of the university's School of Physical Sciences. It was opened in 1874 as a teaching laboratory....
, he started his life-long work on hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
. The death of Lord Rutherford
Ernest Rutherford
Ernest Rutherford, 1st Baron Rutherford of Nelson OM, FRS was a New Zealand-born British chemist and physicist who became known as the father of nuclear physics...
led to his successor, Lawrence Bragg, a pioneer in X-Ray crystallography, becoming the new Cavendish professor of physics in 1938. Bragg became a major supporter of Perutz and his group in those early days.
After World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
, many scientists from the physical side of science turned to biology, bringing with them a new way of thinking and expertise. John Kendrew
John Kendrew
Sir John Cowdery Kendrew, CBE, FRS was an English biochemist and crystallographer who shared the 1962 Nobel Prize in Chemistry with Max Perutz; their group in the Cavendish Laboratory investigated the structure of heme-containing proteins.-Biography:He was born in Oxford, son of Wilford George...
joined Perutz’s group to study a protein closely related to hemoglobin — myoglobin
Myoglobin
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the...
— in 1946. In 1947, the Medical Research Council
Medical Research Council (UK)
The Medical Research Council is a publicly-funded agency responsible for co-ordinating and funding medical research in the United Kingdom. It is one of seven Research Councils in the UK and is answerable to, although politically independent from, the Department for Business, Innovation and Skills...
(MRC), under the guidance of its Secretary Harold Himsworth, decided to form and support the “MRC Unit for the Study of the Molecular Structure of Biological Systems”. The group, which by 1948 also included Hugh Huxley
Hugh Huxley
Hugh Esmor Huxley FRS is a British biologist. He is professor of biology at Brandeis University, in Waltham, Massachusetts, United States....
working on muscle, was joined in 1949 by Francis Crick
Francis Crick
Francis Harry Compton Crick OM FRS was an English molecular biologist, biophysicist, and neuroscientist, and most noted for being one of two co-discoverers of the structure of the DNA molecule in 1953, together with James D. Watson...
, who worked initially on protein crystallography. In 1951 they were joined by James Watson
James D. Watson
James Dewey Watson is an American molecular biologist, geneticist, and zoologist, best known as one of the co-discoverers of the structure of DNA in 1953 with Francis Crick...
.
1953 was an annus mirabilis
Annus mirabilis
Annus mirabilis is a Latin phrase meaning "wonderful year" or "year of wonders" . It was used originally to refer to the year 1666, but is today also used to refer to different years with events of major importance...
: Watson and Crick discovered the double-helical structure of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, which revealed that biological information was encoded in a linear structure and how this information could be duplicated during cell division
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...
. Perutz discovered that the detailed three dimensional structures of proteins, such as myoglobin and hemoglobin could, in principle, be solved by X-ray analysis using a heavy metal atom labeling technique. Hugh Huxley discovered that muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
contraction works by a sliding filament mechanism
Sliding filament mechanism
The sliding filament theory describes a process used by muscles to contract. It was independently developed by Andrew F. Huxley and Rolf Niedergerke and by Hugh Huxley and Jean Hanson in 1954.-Process of movement:...
.
In 1957 the group’s name was changed to the “MRC Unit for Molecular Biology”. Also that year, Vernon Ingram
Vernon Ingram
Vernon M. Ingram, Ph.D., FRS was a German American professor of biology at the Massachusetts Institute of Technology.-Biography:Ingram was born in Breslau, Lower Silesia...
discovered that the disease sickle cell anaemia is caused by a single amino acid change in the hemoglobin molecule and Sydney Brenner
Sydney Brenner
Sydney Brenner, CH FRS is a South African biologist and a 2002 Nobel prize in Physiology or Medicine laureate, shared with H...
joined the Unit. In 1958, Crick’s review “On Protein Synthesis” appeared: this laid out, for the first time, the central dogma of molecular biology
Central dogma of molecular biology
The central dogma of molecular biology was first articulated by Francis Crick in 1958 and re-stated in a Nature paper published in 1970:In other words, the process of producing proteins is irreversible: a protein cannot be used to create DNA....
, the sequence hypothesis
Sequence hypothesis
The sequence hypothesis was first formally proposed in a review “On Protein Synthesis” by Francis Crick in 1958. It states that the sequence of bases in the genetic material determines the sequence of amino acids for which that segment of nucleic acid codes, and this amino acid sequence...
and the adaptor hypothesis
Adaptor hypothesis
The adaptor hypothesis is part of a scheme to explain how information encoded in DNA is used to specify the amino acid sequence of proteins. It was formulated by Francis Crick in the mid-1950s, together with the central dogma of molecular biology and the sequence hypothesis...
. In 1961 Brenner helped discover messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
and, in the same year, he and Crick established that the genetic code
Genetic code
The genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....
was read in triplets.
All this work was accomplished in a single-storey temporary building (The Hut), a few rooms in the Austin Wing, a room with a lean-to glass front (The Greenhouse) and a short sealed off corridor (The Gallery) within the Cavendish laboratory.
Opening of the LMB: 1962
The MRC built a new Laboratory on the outskirts of Cambridge — the LMB — into which the Unit from the Cavendish moved in early 1962. Additionally, Fred Sanger’s Unit which had been housed in the University’s Biochemistry department joined them, as did Aaron KlugAaron Klug
Sir Aaron Klug, OM, PRS is a Lithuanian-born British chemist and biophysicist, and winner of the 1982 Nobel Prize in Chemistry for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes.-Biography:Klug was...
from London. Sanger had invented methods for determining the sequence of amino acids in a protein: he was awarded the Nobel prize
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...
for chemistry in 1958 for the first protein sequence, that of insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
. The new laboratory was opened by Queen Elizabeth II
Elizabeth II of the United Kingdom
Elizabeth II is the constitutional monarch of 16 sovereign states known as the Commonwealth realms: the United Kingdom, Canada, Australia, New Zealand, Jamaica, Barbados, the Bahamas, Grenada, Papua New Guinea, the Solomon Islands, Tuvalu, Saint Lucia, Saint Vincent and the Grenadines, Belize,...
in 1962. Later that year, Kendrew and Perutz shared the Nobel prize for chemistry and Crick and Watson received a share of the Nobel prize for physiology or medicine.
The new LMB had Perutz as its chairman and contained 3 divisions: Structural Studies, headed by Kendrew; Molecular Genetics (Crick); Protein Chemistry (Sanger). In all, there were about 40 scientists but this number rapidly increased, particularly with a large influx of post-doctoral visitors from the US.
Molecular Biology: 1962-
During the next decade, molecular biology the world over flourished, the outline bones of the 1950s now having flesh put on them. The detailed 3-D atomic structures of a series of proteins, and how they function, were deduced. These included myoglobinMyoglobin
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the...
, hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
and chymotrypsin
Chymotrypsin
Chymotrypsin is a digestive enzyme that can perform proteolysis. Chymotrypsin preferentially cleaves peptide amide bonds where the carboxyl side of the amide bond is a tyrosine, tryptophan, or phenylalanine. These amino acids contain an aromatic ring in their sidechain that fits into a...
, the last by David Blow. The genetic code, from evidence around the world, was assembled by Crick. Punctuation signals in the messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
— where to start translating the RNA into a protein sequence, and where to stop — were discovered. Crick suggested how the tRNA molecules — his original adaptors — read the messenger in his wobble hypothesis
Wobble base pair
In molecular biology, a wobble base pair is a non-Watson-Crick base pairing between two nucleotides in RNA molecules. The four main wobble base pairs are guanine-uracil, inosine-uracil, inosine-adenine, and inosine-cytosine . The thermodynamic stability of a wobble base pair is comparable to that...
. Sanger devised new methods for sequencing RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
molecules and then later for DNA molecules (for which he received a second Nobel prize in chemistry in 1980). Much later, this line was extended to include determining the sequence of whole genomes, in which John Sulston played a key role. How tRNA precursor molecules are processed to give a functional tRNA was elucidated by John Smith
John Derek Smith
John Derek Smith FRS was a British Molecular Biologist who participated in many of the major discoveries at the LMB* Born Southampton, England 8 December 1924...
and Sid Altman, and this later led to the discovery of ribozymes. The atomic structure of the first tRNA molecule was solved and zinc fingers discovered by Klug (who received the Nobel prize for chemistry in 1982). The structure of the ATP synthase
ATP synthase
right|thumb|300px|Molecular model of ATP synthase by X-ray diffraction methodATP synthase is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate . ATP is the most commonly used "energy currency" of cells from most organisms...
was solved by John Walker
John Walker
-Politicians:* John Walker , U.S. Senator, public official, and soldier* John Walker , State Treasurer of Missouri...
and Andrew Leslie, for which Walker shared the Nobel prize for chemistry in 1997. The structure of the ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
was solved by Venkatraman Ramakrishnan, for which he shared the Nobel prize for chemistry in 2009.
Diversification
Towards the end of the 1960s decade, it seemed that new problems in biology could be solved using the approaches which proved so successful in molecular biology.Development and C.elegans
Brenner started working on the genetics of the nematode C.elegans in 1965. This group expanded, especially with many foreign visitors who today form the core of C.elegans research. Sulston determined the cell lineage of this small worm and John WhiteJohn White (biologist)
John G White co-developed confocal microscopy and mapped the complete nervous system of C. elegans, consisting of 302 neurons and over 7000 synapses. The study was published in 1986 by the Philosophical Transactions of the Royal Society of London , and is considered to be the first work in the...
the entire wiring diagram of its nervous system. Robert Horvitz, who helped in the cell lineage, was to share the Nobel prize for physiology or medicine with Brenner and Sulston in 2002. Jonathan Hodgkin established the genetic pathway in C.elegans which controls sex determination. John Gurdon
John Gurdon
Sir John Bertrand Gurdon , FRS is a British developmental biologist. He is best known for his pioneering research in nuclear transplantation and cloning. He was recently awarded the Lasker Award.-Career:...
developed the use of the frog oocyte to translate mRNAs.
Peter Lawrence
Peter Lawrence
Peter Anthony Lawrence FRS is a British developmental biologist at the Laboratory of Molecular Biology and the Zoology Department of the University of Cambridge...
came to study pattern formation, helping discover how compartments in Drosophila determine the fly’s body plan. Under his influence, Crick also became interested in morphogenetic gradients and how they may help specify biological patterns.
Immunology
Cesar MilsteinCésar Milstein
César Milstein FRS was an Argentine biochemist in the field of antibody research. Milstein shared the Nobel Prize in Physiology or Medicine in 1984 with Niels K. Jerne and Georges Köhler.-Biography:...
had over many years been working on antibody variation. He was joined in this by Georges Kohler and, together, they discovered how to produce monoclonal antibodies
Monoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
. For this they shared the Nobel prize for physiology or medicine in 1984. This area was extended by Greg Winter
Greg Winter
Sir Gregory Winter FRS is a British pioneer of therapeutic monoclonal antibodies. He invented techniques to both humanise and, later, to fully humanise using phage display, antibodies for therapeutic uses...
who pioneered antibody engineering to make novel human antibodies and antibody fragments. Both monoclonal antibodies and their fragments are now of major medical importance.
Publishing in November 2010 in the journal Proceedings of the National Academy of Sciences Leo James led a research group to discover the ability of the immune system to fight viruses inside infect cells. Standard immunology textbooks taught that once a cell is invaded the body has no alternative but to kill the cell. But the research showed how a protein called TRIM21
TRIM21
Tripartite motif-containing protein 21 also known as E3 ubiquitin-protein ligase TRIM21 is a protein that in humans is encoded by the TRIM21 gene. Alternatively spliced transcript variants for this gene have been described but the full-length nature of only one has been determined...
attacks invaders of the cell which aren't antibodies. This research paves the way for finally finding a cure to the common cold i.e. Rhinoviruses, to noravirus, which causes winter vomiting and to rotavirus, which cause gastroenteritis by utilising and boosting the natural mechanism of attacking cell invaders.
Cell Biology
The emphasis on classical molecular biology shifted towards cell biology and development, so that the Molecular Genetics division was renamed Cell Biology. Mark BretscherMark Bretscher
Mark Bretscher is a British biological scientist and Fellow of the Royal Society. He works at the Medical Research Council Laboratory of Molecular Biology in Cambridge, United Kingdom...
discovered the topological way proteins are arranged in the human erythrocyte membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
and its phospholipid asymmetry
Flippase
Flippases are a family of transmembrane lipid transporter enzymes located in the membrane responsible for aiding the movement of phospholipid molecules between the two leaflets that compose a cell's membrane...
. Richard Henderson
Richard Henderson (molecular biologist)
Richard Henderson FRS is a Scottish molecular biologist and pioneer in the field of electron microscopy of biological molecules.-Career:...
and Nigel Unwin
Nigel Unwin
Nigel Peter Nigel Tripp Unwin FRS is a British neuroscientist, Emeritus Scientist, and was Joint Head of Neurobiology Division, Laboratory of Molecular Biology from 2003 until 2008.-Life:...
developed electron crystallography
Electron crystallography
Electron crystallography is a method to determine the arrangement of atoms in solids using a transmission electron microscope .- Comparison with X-ray crystallography :...
to determine the structure of two dimensional arrays, applying this to the bacterial purple protein, bacteriorhodopsin
Bacteriorhodopsin
Bacteriorhodopsin is a protein used by Archaea, the most notable one being Halobacteria. It acts as a proton pump; that is, it captures light energy and uses it to move protons across the membrane out of the cell...
. Barbara Pearse
Barbara Pearse
Barbara Pearse is a British biological scientist and Fellow of the Royal Society. She works at the Medical Research Council Laboratory of Molecular Biology in Cambridge, United Kingdom....
discovered the major components of clathrin-coated vesicles, structures formed during endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
, and a low resolution structure of the cage-like lattice around them was determined. How proteins become localised to different parts of the cell — such as to the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
, Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
or the plasma membrane — and the role of this in cell polarity, have been elucidated by Bretscher, Hugh Pelham and Sean Munro. The spindle pole bodies
Spindle pole body
The spindle pole body is the microtubule organizing center in yeast cells, functionally equivalent to the centrosome. Unlike the centrosome the SPB does not contain centrioles. The SPB organises the microtubule cytoskeleton which plays many roles in the cell...
— the large structures in yeast cells which act as the foci to which chromosomes are moved during mitosis — have been purified and a low resolution structure of them deduced by John Kilmartin.
A continuing interest has been the structure of chromosomes. This was initiated by a visitor, Roger Kornberg, who discovered the first level of condensation of DNA, the nucleosome
Nucleosome
Nucleosomes are the basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound around a histone protein core. This structure is often compared to thread wrapped around a spool....
, and continues with the focus on understanding the higher orders of folding DNA.
Neurobiology
A new division of Neurobiology was created in 1993 with a wide variety of topics. Unwin has further developed electron crystallography and solved the structure of the acetylcholine receptorAcetylcholine receptor
An acetylcholine receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.-Classification:...
, which activates many neurons. Michel Goedert has identified variant proteins associated with Alzheimer’s disease.
Instrumentation
Scientific advances often depend on technological advances: the LMB has been at the forefront of many of these. Some major examples include nucleic acid sequencing, protein and antibody engineering, construction of new X-ray equipment and the invention of the scanning confocal microscope.Famous alumni
Scientific staff of the LMB who have shared a Nobel prize are:- Frederick SangerFrederick SangerFrederick Sanger, OM, CH, CBE, FRS is an English biochemist and a two-time Nobel laureate in chemistry, the only person to have been so. In 1958 he was awarded a Nobel prize in chemistry "for his work on the structure of proteins, especially that of insulin"...
(twice) - John KendrewJohn KendrewSir John Cowdery Kendrew, CBE, FRS was an English biochemist and crystallographer who shared the 1962 Nobel Prize in Chemistry with Max Perutz; their group in the Cavendish Laboratory investigated the structure of heme-containing proteins.-Biography:He was born in Oxford, son of Wilford George...
- Max PerutzMax PerutzMax Ferdinand Perutz, OM, CH, CBE, FRS was an Austrian-born British molecular biologist, who shared the 1962 Nobel Prize for Chemistry with John Kendrew, for their studies of the structures of hemoglobin and globular proteins...
- Francis CrickFrancis CrickFrancis Harry Compton Crick OM FRS was an English molecular biologist, biophysicist, and neuroscientist, and most noted for being one of two co-discoverers of the structure of the DNA molecule in 1953, together with James D. Watson...
- Aaron KlugAaron KlugSir Aaron Klug, OM, PRS is a Lithuanian-born British chemist and biophysicist, and winner of the 1982 Nobel Prize in Chemistry for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes.-Biography:Klug was...
- César MilsteinCésar MilsteinCésar Milstein FRS was an Argentine biochemist in the field of antibody research. Milstein shared the Nobel Prize in Physiology or Medicine in 1984 with Niels K. Jerne and Georges Köhler.-Biography:...
- John WalkerJohn Walker-Politicians:* John Walker , U.S. Senator, public official, and soldier* John Walker , State Treasurer of Missouri...
- Sydney BrennerSydney BrennerSydney Brenner, CH FRS is a South African biologist and a 2002 Nobel prize in Physiology or Medicine laureate, shared with H...
- John Sulston
- Venkatraman Ramakrishnan
Visitors who have received a Nobel prize for work done, or initiated, at the LMB include:
- Jim WatsonJames D. WatsonJames Dewey Watson is an American molecular biologist, geneticist, and zoologist, best known as one of the co-discoverers of the structure of DNA in 1953 with Francis Crick...
- Sid Altman
- Georges Kohler
- Robert Horvitz
- Roger Kornberg
- Andrew FireAndrew FireAndrew Zachary Fire is an American biologist and professor of pathology and of genetics at the Stanford University School of Medicine. He was awarded the 2006 Nobel Prize for Physiology or Medicine, along with Craig C. Mello, for the discovery of RNA interference...
- Thomas A. SteitzThomas A. Steitz-Publications:* Steitz, T. A., et al. , nsls newsletter, .* Steitz, T. A., et al. , NSLS Activity Report .-External links:* , from the Office of Scientific and Technical Information, United States Department of Energy...
- Marty Chalfie
In addition, many alumni have gained great distinction which has been recognised by elections to learned bodies. A link to a list of past members of the LMB can be found below.
Administrative structure
The early success of the LMB was in no small way helped by the simple administrative environment. From outside the LMB, the parent MRC ensured that the triennial assessment had a light touch: only a brief explanation of past achievements and an indication of where future plans lay were required by the external committee. Their recommendations were simply advisory, leaving the division leaders a free hand as to how to run their affairs: they were assumed to know best.Within the LMB, Perutz’s criterion of how to arrange things was that the act of doing science should be facilitated at all levels. The LMB had a single budget: there were no personal budgets or equipment — everything was communal, which made running the lab cheaper. It had state of the art equipment and was well financed by the MRC. Chemical reagents, glassware and other expendibles could be withdrawn from an extremely well stocked store with no more than a signature. Key to the smooth functioning of the lab was Michael Fuller, who was responsible for its day-to-day running.
There was no overt hierarchy; everyone was on first-name terms. Most members of the lab met freely in the canteen, situated at the top of the building with a view across Cambridge, for mid-morning coffee, lunch and afternoon tea. This assisted inter-divisional communication and collaboration.
Today the LMB has around 340 scientists, of whom 130 are postdoctoral visitors and 90 students.
See also
- John Finch; 'A Nobel Fellow On Every Floor', Medical Research Council 2008, 381 pp, ISBN 978-1840469-40-0; this book is all about the MRC Laboratory of Molecular Biology, Cambridge.