MRC Laboratory of Molecular Biology

Coordinates: 52°10′35″N 0°08′35″E / 52.1763°N 0.1430°E / 52.1763; 0.1430
Source: Wikipedia, the free encyclopedia.

MRC Laboratory of Molecular Biology
AbbreviationMRC LMB
Location
Coordinates52°10′35″N 0°08′35″E / 52.1763°N 0.1430°E / 52.1763; 0.1430
FieldsMolecular biology
Director
Jan Löwe
Parent organization
Medical Research Council
Websitewww2.mrc-lmb.cam.ac.uk

The Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) is a research institute in Cambridge, England, involved in the revolution in molecular biology which occurred in the 1950–60s. Since then it has remained a major medical research laboratory at the forefront of scientific discovery, dedicated to improving the understanding of key biological processes at atomic, molecular and cellular levels using multidisciplinary methods, with a focus on using this knowledge to address key issues in human health.[1][2][3]

A new replacement building constructed close by to the original site on the Cambridge Biomedical Campus was opened by Her Majesty the Queen in May 2013.[4] The road outside the new building is named Francis Crick Avenue after the 1962 joint Nobel Prize winner and LMB alumnus, who co-discovered the helical structure of DNA in 1953.[5]

History

Origins: 1947-61

Cavendish laboratory, he started his lifelong 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

James Watson
.

1953 was an

sliding filament mechanism
.

In 1957 the group's name was changed to the “MRC Unit for Molecular Biology”. Also that year,

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.[6]

Opening of the LMB in 1962

The LMB building until 2012. The white structure is a new lecture hall added to the old building.

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,

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 LMB building was incorporated into the new Addenbrooke's Hospital complex as this was constructed in the 1970s.[7]

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.[6]

Molecular Biology: after 1962

During the 1960s, 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

Venkatraman Ramakrishnan, for which he shared the Nobel Prize for Chemistry in 2009.[11]

1960s: Development and C. elegans

A laboratory at the new LMB building in June 2013

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.

Sydney Brenner started working on the genetics of the nematode

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, sharing the 2012 Nobel Prize for Physiology or Medicine for his earlier work showing that genetic information remains intact during development.

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.

Immunology

Greg Winter[12] who pioneered antibody engineering using phage display to make novel human antibodies and antibody fragments, for which he shared the Nobel Prize in Chemistry in 2018.[13]
Both monoclonal antibodies and their fragments are now of major medical importance.

Activation-induced (cytidine) deaminase. This fundamental discovery is the keystone to understanding the molecular mechanism by which organisms can produce a diverse repertoire of antibodies to recognise new pathogens. This is of wider importance in understanding the role of directed mutagenesis and DNA repair in physiology. Finally, the molecular mechanisms elucidated by Neuberger may be of great importance in understanding the mutational pattern of kataegis
in breast cancer. Sadly, Michael Neuberger died from myeloma – the irony of which was not lost on him.

Cell biology

Atrium of the new building at night

The emphasis on classical molecular biology shifted towards cell biology and development, so that the Molecular Genetics division was renamed Cell Biology.

plasma membrane — and the role of this in cell polarity, have been elucidated by Bretscher, Hugh Pelham[14] 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.[15]

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.

Neurobiology

A new division of Neurobiology was created in 1993 with a wide variety of topics. Nigel Unwin has further developed electron crystallography and solved the structure of the acetylcholine receptor, 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.[6]

Administrative structure

A public lecture at the new building

The LMB has a deliberately simple administrative environment.[16] From outside the LMB, the parent MRC ensured that the quinquennial 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.[citation needed]

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. It had state-of-the-art equipment and was well financed by the MRC.[citation needed] Chemical reagents, glassware and other expendables could be withdrawn from a single store with only a signature required. Key to the smooth functioning of the lab was Michael Fuller, who was responsible for its day-to-day running.[17]

There was no overt hierarchy; everyone was on first-name terms. Most members of the lab met freely in the canteen, which was said to assist inter-divisional communication and collaboration.[6] Today the LMB has around 450 scientists, of whom 130 are postdoctoral researchers and 110 students. The new building (situated on the Cambridge Biomedical Campus) was opened in 2013[4] and has four seminar rooms named after LMB scientists: Sydney Brenner, Aaron Klug, César Milstein and Frederick Sanger, as well as a lecture theatre named after the late Max Perutz.

Groups at the LMB

As of 2023 there are around fifty group leaders

Nucleic Acid Chemistry and Structural Studies. As of 2023
group leaders include the following people:

Emeritus

The LMB is also home to a number of Emeritus Scientists, pursuing their research interests in the Laboratory after their formal retirement[18] including:

Notable people

Nobel recipients

Scientific staff of the LMB who have been awarded individually or have shared Nobel Prizes[31][32][33] are:

Visitor recipients of Nobel Prizes

Visitors who received a Nobel Prize for work done, or initiated at the LMB and alumni include:

Notable LMB alumni

[49]

References

  1. ^ "MRC Laboratory of Molecular Biology". www.ukri.org. Retrieved 1 March 2022.
  2. ^ Brackley, Paul (12 December 2018). "Dr Jan Löwe on the next scientific frontier for the MRC Laboratory of Molecular Biology". Cambridge Independent. Retrieved 1 March 2022.
  3. ^ Brackley, Paul (14 February 2018). "Dr Jan Löwe says he's 'humbled' to take over as director of MRC Laboratory of Molecular Biology". Cambridge Independent. Retrieved 1 March 2022.
  4. ^ a b "Her Majesty the Queen opens the new MRC Laboratory of Molecular Biology". Cambridge University. 23 May 2013. Retrieved 20 June 2013.
  5. OCLC 865330798
    .
  6. ^
    ISBN 978-1-84046-940-0
  7. ^ "The LMB- present and future… University of Cambridge". 17 February 2014.
  8. ^ J. A. Steitz, (1969) "Polypetide Chain Initiation: Nucleotide Sequences of the Three Ribosomal Binding Sites in Bacteriophage R17 RNA," Nature 224 (5223):957–964.
  9. ISBN 978-1840469-40-0
    .
  10. PMID 27459055
    .
  11. ^ Nobel Laureates in Chemistry 2009
  12. ^
    PMID 23741620
    .
  13. ^ World2018-10-03T11:06:00+01:00, Chemistry. "Live blog: directed evolution takes chemistry Nobel prize". Chemistry World. Retrieved 23 February 2022.{{cite web}}: CS1 maint: numeric names: authors list (link)
  14. ^ "PELHAM, Sir Hugh (Reginald Brentnall)". Who's Who. Vol. 2016 (online Oxford University Press ed.). A & C Black. (Subscription or UK public library membership required.)
  15. ^ a b "MARTIN, Dr John Vincent". Who's Who. Vol. 2016 (online Oxford University Press ed.). A & C Black. (Subscription or UK public library membership required.)
  16. PMID 23099394
    .
  17. S2CID 28008877
    .
  18. ^ a b "Group Leaders – MRC Laboratory of Molecular Biology". 2020. Archived from the original on 26 October 2014.
  19. ^ "HASTINGS, Dr Michael Harvey". Who's Who. Vol. 2016 (online Oxford University Press ed.). Oxford: A & C Black. (Subscription or UK public library membership required.)
  20. ^ "LÖWE, Dr Jan". Who's Who. Vol. 2016 (online Oxford University Press ed.). Oxford: A & C Black. (Subscription or UK public library membership required.)
  21. PMID 21576387
    .
  22. doi:10.1093/ww/9780199540884.013.U256393. (Subscription or UK public library membership
    required.)
  23. doi:10.1126/science.caredit.a1100063
    .
  24. PMID 21914843. Open access icon
  25. PMID 25519114
    .
  26. ^ "BIENZ, Dr Mariann, (Lady Pelham)". Who's Who. Vol. 2016 (online Oxford University Press ed.). A & C Black. (Subscription or UK public library membership required.)
  27. ^ "Dr Richard Crowther FMedSci FRS". London: Royal Society. Archived from the original on 17 November 2015.
  28. ^ "CROWTHER, Dr Richard Anthony". Who's Who. Vol. 2016 (online Oxford University Press ed.). Oxford: A & C Black. (Subscription or UK public library membership required.)
  29. ^ "EVANS, Dr Philip Richard". Who's Who. Vol. 2016 (online Oxford University Press ed.). Oxford: A & C Black. (Subscription or UK public library membership required.)
  30. ^ "LESLIE, Dr Andrew Greig William". Who's Who. Vol. 2016 (online Oxford University Press ed.). Oxford: A & C Black. (Subscription or UK public library membership required.)
  31. ISBN 978-1-84046-940-0
    ; this book is all about the MRC Laboratory of Molecular Biology, Cambridge.
  32. ^ LMB Archives
  33. ^ The Nobel Laureates of the LMB
  34. PMID 24380948
    .
  35. S2CID 73986989
    .
  36. PMID 15318208
    .
  37. PMID 15003624
    .
  38. PMID 11976669
    .
  39. S2CID 1037231
    .
  40. ^ "CHOTHIA, Cyrus Homi". Who's Who. Vol. 2016 (online Oxford University Press ed.). A & C Black. (Subscription or UK public library membership required.)
  41. EThOS ID uk.bl.ethos.455951
  42. ^ "Toby (James) Gibson".
  43. doi:10.1093/ww/9780199540884.013.U25975. (Subscription or UK public library membership
    required.)
  44. ^ "NAGAI, Kiyoshi". Who's Who. Vol. 2016 (online Oxford University Press ed.). Oxford: A & C Black. (Subscription or UK public library membership required.)
  45. PMID 24532658
    .
  46. doi:10.1093/ww/9780199540884.013.U45811. (Subscription or UK public library membership
    required.)
  47. PMID 9927456. Open access icon
  48. doi:10.1093/ww/9780199540884.013.U4000615. (Subscription or UK public library membership
    required.)
  49. ^ "LMB Alumni List". MRC LMB Alumni List. Archived from the original on 11 October 2022. Retrieved 16 March 2023.

External links

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