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BRIG The Papers of Asa Briggs
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BRLW The Papers of Professor Harold Barlow
BRME The Papers of Jackie Broome
BRNT The Papers of Correlli Barnett
BRTS The Papers of Mark Bretscher
BRUN The Papers of Sir Frederick Brundrett
BRWN The Papers of Lord Brown
BSAN Transcripts of Basil Sanderson's diaries
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The Papers of Mark Bretscher

Title The Papers of Mark Bretscher
Reference GBR/0014/BRTS
Creator Bretscher, Mark, b 1940, biologist
Covering Dates 1936–2013
Extent and Medium 12 archive boxes
Repository Churchill Archives Centre
Content and context

Mark Bretscher was born in Cambridge, UK, on 8th January 1940; he is the son of the nuclear physicist Egon Bretscher.

Educated at Abingdon School, Berkshire, he went on to study Chemistry at the University of Cambridge. Bretscher moved from the Chemistry department to Biology in 1961 where he started a PhD under Sydney Brenner initially in the Cavendish Laboratory and then at the new MRC laboratory of Molecular Biology. His worked focused on the use of synthetic polyribonucleotides to investigate the genetic code. After completing his PhD in 1964, Bretscher took up a year-long Postdoctoral Fellowship at Stanford University, California with Dr. Paul Berg. Upon his return from Stanford in 1965, he continued with his work on protein biosynthesis as a Research Fellow at Gonville and Cauis College, Cambridge.

In 1970, Bretscher began to feel that his work on protein biosynthesis was in an overcrowded research area, so instead switched to looking at cell membranes - a new area of study for the MRC Laboratory. From studies on human erythrocytes he was the first to show that the lipid bilayer structure for biological membranes was asymmetric, and was spanned by specific membrane proteins.

From 1974-75 Bretscher took up a visiting Professorship at the Department of Biochemistry and Molecular Biology, Harvard University; here he taught a final year course on cell membranes. On returning to Cambridge, he began studies of how animal cells move.

Bretscher was joint head of the Cell Biology Division at the MRC Laboratory of Molecular Biology, Cambridge from 1986 -1995, sharing the post with Peter Lawrence and then Hugh Pelham. He became a fellow of the Royal Society in 1985.

Since 2005 Bretscher has been an emeritus scientist at the Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge. In 2009, he discovered that amoebae and human neutrophils (white blood cells) can swim, which he describes as, "perhaps my most important contribution yet".

The collection held by Churchill Archives contains the professional scientific papers of Mark Bretscher, starting from his early work on the genetic code and protein biosythesis, then moving into his work on cell membranes and cell movement. Predominantly working papers with some correspondence and photographs.

The papers were received from Mark Bretscher in 2012, with an additional accession of 3 correspondence files and slides in 2015.

The collection was gifted to the Churchill Archives Centre in well-ordered files reflecting Bretscher's use of the material. This order has been retained.

Access and Use

The collection is open for consultation by researchers using Churchill Archives Centre, Churchill College, Cambridge. Churchill Archives Centre is open from Monday to Friday, 9am-5pm. A prior appointment and two forms of identification are required.

Researchers wishing to publish excerpts from the papers must obtain prior permission from the copyright holder and should seek advice from Archives Centre staff.

Please cite as Churchill Archives Centre, The Papers of Mark Bretscher, BRTS

Further information

The catalogue includes the descriptions of the material prepared by Mark Bretscher himself. A copy of Bretscher's original list for files 1-39 can be found at BRTS 1. This catalogue also includes a separate note of Bretscher's personal comments and reflections on the material.

A copy of this catalogue is available for consultation at Churchill Archives Centre, Cambridge, the National Register of Archives, London and on the Janus website, http://janus.lib.cam.ac.uk/.

This description was prepared by Elizabeth Courtney at Churchill Archives Centre in August 2012, using information provided by Mark Bretscher, Who's Who, Mark Bretscher's Curriculum Vitae and from John Finch's book 'A Nobel Fellow on Every Floor' (published 2008).

Index Terms
Molecular Biology
Bretscher, Mark Steven (b 1940) biologist
University of Cambridge. Mrc Laboratory of Molecular Biology
University of Cambridge
Churchill/BRTS contains:
1 The coding properties of random synthetic messengers. Testing the coding properties of random synthetic messengers; investigating the attachment of the growing polypeptide to tRNA. Also contains a list by Mark Bretscher describing the contents of all files and offering personal comments.
3 Files.
Oct 1961-Dec 1962
2 The coding properties of random synthetic messengers. Continuing from previous papers; devising methods to separate the released polypeptide from peptidyl-tRNA.
4 Files.
Oct 1962-Nov 1963
3 The coding properties of random synthetic messengers. Continuing from previous papers; using results to measure the termination coding properties of different mRNAs.
1 File.
Nov 1963-Oct 1964
4 Stanford: Attempts to isolate a stable complex of tRNA. Time at Stanford: attempt to isolate a stable complex of tRNA, the alanine activating enzyme and ATP (using a stable analogue of alanyl-adenylate, alaninol-adenylate); investigated to find out if chloramphenicol terminates the growing polypeptide chain; attempt to study chain termination with minimal messengers of the type AAAUAG. 1966 notes missing.
4 Files.
Sept 1964-Dec 1965
5 Study Termination with Phage RNA. Study termination with phage RNA (amber mutant which codes for a hexapeptide). Fails to find a chain-terminating tRNA and tentatively concludes it doesn't exist.
2 Files.
Nov 1966-Apr 1968
6 Circular fd DNA. Finds circular fd DNA acts as a messenger DNA and codes for a few distinct peptides, showing that a mRNA doesn't need an end to initiate protein synthesis.
3 Files.
Oct 1966-Nov 1971
7 Labelling agents and Surface Labelled Erythrocytes. Attempts to develop a label and surface labelling erythrocytes. Some notes by Susan Brownlee, Bretscher's assistant at the time.
2 Files.
Aug 1969-Oct 1970
8 Fingerprints of labelled RBC bands and lipid analysis. Fingerprints of labelled RBC bands and lipid analysis.
1 File.
Feb 1970-Feb 1972
9 Oddments and X-ray studies on frog sciatic myelin and derivatized myelin. Jan - Dec 1972: Oddments. Dec 1972 - March 1973: X-ray studies on frog sciatic myelin and derivatized myelin (mainly iodoacetyated) to see whether lipid asymmetry can be seen. With much help from R. Kornberg.
1 File.
Jan 1972-Mar 1973
10 Bacterial Lipids. Jun 1973 - Mar 1974: Looking at bacterial (B. megaterium) lipids. April 1974 - Mar 1975: preparing lectures/taught a final year course on membranes at Harvard.
1 File.
Jun 1973-Mar 1975
11 Lipids. Experiments looking at lipids: e.g. cholesterol exchange between vesicles, endocytosis by looking at sphingomyelin (SM) and its degradation by external sphingomyelinase. Attempts to make anti-SM, coupling SM to resin/BSA using proprionyl-SM (PSM) after Metcalf and Burgen's claims to have made anti-phosphoryl-choline antibodies. Investigation of endocytosis with various markers.
1 File.
Mar 1975-Oct 1976
12 Electron Microscopy. Electron microscopy, mainly examining freeze-fracture planes with Sue Whytock (ex Branton) for gradients of particles (proteins) in the fracture plane on cells which might be migrating, mainly chick heart fibroblasts (CEF). Expected to find such gradients if lipid flow were correct: but the scheme was unsuccessful, partly because the fracture planes are not quite flat, which leads particles in different regions of a large fracture plane to look quite different. In addition, experiments looking to see whether glycolipids (expected to be in coated pits, where ferritin is bound) are ferritin receptors; assayed by looking for the binding of Ft to monolayers of lipids when examined in the electron microscope.
1 File.
Feb 1976-Mar 1978
13 Experiments with Peter Stern. Experiments with Peter Stern to see if Forssman antigen (a glycolipid) caps on motile cells. Attempt to study carbohydrate sequences: try to make a hot label for aldehyde residues, try to break polypeptide backbone of main erythrocyte glycoprotein with proteases, hydrazine (after A. Kobata) and later a cobalt complex reputed to act as a nonspecific protease.
1 File.
Apr 1978-Dec 1978
14 Hydrazinolysis on Other Glycoproteins. More hydrazinolysis on other glycoproteins.
1 File.
Dec 1978-Aug 1979
15 Hydrazinolysis on Other Glycoproteins. More hydrazinolysis on other glycoproteins. Looking at Thy-1 and H63 antigens on fibroblasts to see how much of each is in coated pits and finds they appeared to be excluded.
1 File.
Sept 1979-Sept 1980
16 Oligosaccharides. More oligosaccharides: attempts to label the reducing ends with tyramine, which can then be radioiodinated. Giant HeLa cells, labelled to detect low density lipoproteins (LDL) and transferrin receptors.
1 File.
Oct 1980-Sept 1982
17 Recycling of Transferrin Receptors. Recycling of transferrin receptors (TFRs) on HeLa cells, with Jeff Bleil. Experimenting with fibronectin fragments.
1 File.
May 1981-Feb 1984
18 Ferritin receptors on Giant HeLa cells. Ferritin receptors on Giant HeLa cells.
1 File.
Sept 1980-Jun 1983
19 Time at Stanford. Time at Stanford; experimenting with proteoglycans.
1 File.
Mar 1984-Aug 1985
20 Fly Eggs and Embryos. Experiments with fly eggs/embryos (particularly shibire mutant), fibronectin and laminin.
1 File.
Apr 1985-Mar 1986
21 Blocking Endocytosis. Attempts to block endocytosis by putting a blocking stick into it, an idea suggested by Jim Rothman: used microtubules, then TMV (tobacco mosaic virus) rods, then asbestos fibres.
1 File.
May 1986-Apr 1987
22 Reducible reagents for labelling the cell surface. Producing reducible reagents for labelling the cell surface and recycling. Recycling of the fibronectin receptor.
1 File.
Jun 1987-Jan 1989
23 Fly Embryos. Experimenting with fly embryos; under the belief that the syncitial state may be like a giant HeLa cell, where a polarised endocytic cycle caps oscar RNA and other posterior determinants (cross-linked somehow and attached to the inner surface of the membrane) whilst bicoid RNA may be attached to some circulating receptor. Attempted to express TFRs (transferrin receptors) in the plasma membrane of early embryos.
1 File.
Jan 1989-Apr 1990
24 Integrin Circulation. Measured the circulation of several integrins, all those for which appropriate antibodies and cells bearing them could be found.
1 File.
Apr 1990-Apr 1991
25 Cell movement under a polarised endocytic cycle. Investigating whether all that is needed for a cell to move is that their feet should be undergoing a polarised endocytic cycle. Examined using a substratum of antibodies to either the transferrin receptors (TFR) (which circulates) or LFA-1 (which does not circulate) and JY cells.
1 File.
Apr 1991-Dec 1992
26 Constructs of Thy1 and lysozyme-LDL (low density lipoproteins) receptor. Various Thy1 and lysozyme-LDL (low density lipoprotein) receptor constructs: with the aim of making circulating and non-circulating derivatives of a surface protein in motile Peer cells and examining their behaviour on anti-Thy1 or anti-lysozyme substrata (related to work in BRTS 25).
2 Files.
Dec 1991-Mar 1993
27 Expressing Transferrin Receptors in Flies. Mainly expressing transferrin receptors (TFRs) in flies. The emphasis was now to look at developing oocytes where the localisation of bicoid RNA and oscar RNA first occurs: looking for a polarised endocytic cycle.
1 File.
Apr 1993-Nov 1993
28 Fly Studies. Fly studies continued.
2 Files.
Sept 1993-Nov 1995
29 Uptake of a surface label FM1-43 in goldfish keratocytes. Attempted to look at the uptake of a surface label, FM1-43, in gold fish keratocytes (a very swift cell) with Leon Lagnadeo. Also constructed innumerable cell constructs.
1 File.
Nov 1995-Dec 1996
30 Cell Lines. More cell lines (which were never used); Investigation of ruffles on KB cells.
2 Files.
Jan 1997-Sept 1998
31 Dictyostelium Discoideum. Dictyostelium discoideum (DD): made various transformants expressing e.g. TFRs (transferrin receptors). Also attempted to mutagenise DD to get ts mutants.
1 File.
Sept 1998-Dec 1999
32 Method for making ts mutants in dictyostelium discoideum. Devised a method for making ts mutants in dictyostelium discoideum (DD); made ts mutants in gene for NSF (gene for key membrane transport protein). Success of this depended in part on the high rate of homologous recombination (HR) that was found at this site. Most of the properties of these mutants — in particular their lack of locomotion at the restrictive temperature — were studied by C. Thompson and D. Traynor.
3 Files.
Dec 1999-Aug 2001
33 DNA Constructs. Made DNA constructs to make ts mutants in Sec1. This failed, in part due to low homologous recombination (HR) at this site.
2 Files.
May 2001-May 2002
34 Making ts Mutants. Try to make ts mutants in p97 (a homologue of NSF (type of key membrane recycling gene), supposed at that time partly to replace NSF in some membrane transport steps). Again, low homologous recombination (HR) compared to NSF site, coupled with the role of p97 becoming less clear, led to abandonment of project.
1 File.
Jul 2001-May 2003
35 Enhancing Homologous Recombination. Devised a new method for enhancing homologous recombination (HR) at the Sec1 site: this involved constructing a strain having a single lox site adjacent to the Sec1 gene and using a mutagenising vector having a single lox site, the transformation being done in the presence of CRE recombinase. This enabled isolation of several ts mutants in the Sec1 gene. These were studied by M. Clotworthy and R. Kay's group.
2 Files.
Dec 2003-May 2005
36 Improving Homologous Recombination. Further studies trying to improve homologous recombination at the Sec1 site using single lox sites.
1 File.
Apr 2004-Nov 2004
37 Relocating Sec1 Gene. Moved the essential gene Sec1 from its chromosomal site to lie next to the NSF gene: to see whether the latter's high level of homologous recombination would be shared by Sec1 in this new site.
2 Files.
Dec 2002-Dec 2003
38 Isolating ts mutants in a dynamin gene. Attempts to isolate ts mutants in a dynamin gene, which failed. Began experiments to see if amoebae can move at an interface (i.e. swim).
4 Files.
May 2005-Apr 2009
39 Discovery that amoebae and human neutrophils can swim. Discovery that amoebae and human neutrophils can swim, which has implications for how they move.
1 File.
Nov 2008-Dec 2009
40 Correspondence (file 1, as described by Mark Bretscher). 1. Satirical note from notice board by Perutz after public complaints of the brain drain (1970s). . 2. Note from Crick on my draft paper reporting discovery of lipid asymmetry in erythrocytes (Nature, 1972). 3. Note from Crick on my draft paper reporting experiments on lipid asymmetry in erythrocytes (JMB, 1972). 4. Note from Gurdon on birth of our son, Andrew (1981). . 5. Card to a group in Division of Cell Biology from Crick thanking us for some flowers we sent him when he was recovering from a depression after the poor reception his Nature paper received on chromosome structure in Nature (1971). . 6. Reprint of Physics Today about life at Harwell by Alex Langsdorf presented to me by my father (1960). 7. Letter from Martynas Ycas (who authored one of the first papers on genetic coding (with George Gamow) (1969). 8. Note from notice board by Perutz about some temporary speech difficulties (1977). 9. 2 notes from Gurdon about transfer of my assistant Sue Whytock to him (1977). 10. Note from Kendrew asking me (via Gillian Harris) to referee a paper. 11. Letter from Khorana thanking me for a review with O.W.Jones (1966). 12. Reprint of Perutz's paper on haemoglobin signed by Brenner (1954). 13. Note from Kendrew unable to come to a garden party (1976). 14. Note from Klug on being unable to come to a party (1980). 15. Letter from Crick about Unwin's nomination for EMBO (1976). 16. Letter from Tony Hewish after his Nobel Prize (1974). 17. Letter from Hans Kornberg accepting summer party invitation (1976). 18. Card by Brenner from Jonathan Karn's lab door (I think). Brenner had a very close relationship with Karn. 19. Note from Perutz about review I wrote in 1973. 20. Letter from Jeremy Prynne (Caius Librarian); I had presented a copy of Watson's 'Double Helix' inscribed for Caius with the words, by Watson, 'For the encouragement of excentricity'! This was stolen from their library. 21. Letter from Brenner with PhD examiners' reports (1964). 22. Examiner's reports on my thesis (1964) for the PhD (I was allowed to rewrite it and subsequently got the degree). The first lengthy report was by McQuillen (later Vice Master of Churchill) and Ken Burton. Also, letter from university registrar (FM Algate) telling me I had failed my PhD (1964). 23. Letter from Brenner on failed PhD (1965). 24. Letter from Perutz on failed PhD (1964). 25. Letter from John Smith on failed PhD (1964). 26. Note from Khorana (1968). 27. Letter from Sanger (1965) about a review I was to write with OW Jones III. 28. Letter from Klaus Weber (1970). 29. Card from Sir Rudolph Peters about uncompleted chat at a feast (1973). 30. Note from Paul Berg (1970). 31. Any comments about a paper, from Crick. 32. Note from Watson (1972). 33. Note from Kendrew about winter party (1969). 34. Letter from Ochoa about purification of the newly discovered protein synthesis initiation factors (1967). 35. Note from Perutz about some reference I needed (1970). 36. Letter to Marianne Grunberg-Manago about a bet between Crick and Rich which I adjudicated (1967). 37. Letter from Rev Hugh Montefiore about being a bishop; he had been dean of Caius (1971). 38. Notes by Perutz for a general talk on molecular biology (~1965). 39. Notice by Brenner telling others not to interfere with his samples on a radioactivity counter (1965). 40. Notes by Crick on Gramicidin S I found in 1972 (in the Cold Spring Harbour Symposium volume for 1948), probably dating from late 1950s. 41. In 1972 Walter Goad from Los Alamos (who went on to found Genbank) spent a sabbatical here. Towards the end of his stay Crick thought he should have been asked to give an informal talk and went round the lab trying to persuade people to listen to Goad. He discussed the problem of how the lac repressor finds the lac operator (a unique 20bp sequence, there being only a few repressors/cell). I sat near the back, with Brenner; he passed this note to me: 'Brenner's equation Biology + Gas Laws = Boredom'. 42. Letter to and two from Margaret Gowing about my father (1973). 43. 5 Letters from Paul Berg. 44. First draft of Nature letter on lipid flow (1976).
1 file.
41 Correspondence (file 2, as described by Mark Bretscher). 45. 2 cards from Tom Kornberg (to me Barbara Pearse, Graeme Mitchison and Peter Lawrence (known as PW or PC) (1976). 46. Letter from Klaus Weber (1976). . 47. Series of letters from Roger Kornberg (in no particular order; 1974-80). 48. Letter from Margaret Clarke (1974). 49. Joke letter from, I think, Tom Kornberg (1977). 50. Letters from Joan Steitz and 1 from Tom + card (early 1970s). 51 Letter from Jim Watson (1998). 52. Note from Walter Gilbert (1963). 53. Note/invitation from Fred Sanger (1970 and 1991). 54. Note from Kendrew (1970s). 55. Notes from Brenner on appointment as head of division (1984). 56. 4 notes from Fred Sanger (2000s; my wife and I frequently took Fred and Joan some casseroled stew to help with the cooking, Joan refused, and Fred hated, cooking.) 4 notes of a hundred. 57. Letter from Ephraim Katchalski (President Kazir) (1962). 58. Letter from Tony Stretton and my reply (about the lack of any reference to my PhD work (done in January 1064) in which I found that a codon for polypeptide chain termination appeared to be made of Us and As; Stretton and Brenner published this in Nature in 1965) (1965). 59. Note from Fritz Lipmann (1965). 60. Note from Marshall Nirenberg (1962). 61. 3 letters from Seymour Benzer about a Gordon Conference he was organizing (1964). 62. Gordon Conference photograph, 1972 . 63. Program for Kendrew memorial (1997). 64. Program for Perutz memorial (2002). 65. BBC program for the 'Thread of Life' by Kendrew (1963). 66. Letter from JD Robertson (of Davson-Danielli-Robertson membrane scheme) + reply (1971). 67. Letters to/ from Dan Branton (1976, 1979). 68. Correspondence with Martin Raff & Av Mitchison (1975). 69. Letter to the Guardian after talking to Mr Tucker (1977). 70. Correspondence with Jon Singer, Ted Steck, Martin Morrison on polarity of erythrocyte membranes (1971,2). 71. Letter from John Tooze about forming EMBO Journal (1981).
1 file.
42 Correspondence (file 3, as described by Mark Bretscher). 72. Letter from me to Crick and his reply; reference to Garen was to a letter he published in Science about the history of nonsense codons. I wrote a letter for Science, pointing out my contributions from 1964 which Brenner ignored, and sent a copy to Crick for his comments. Science did not publish my letter (2002). 73. Letter from me to Crick (2003) and reply. In 2003, Watson gave a talk at the DNA 40th anniversary in Cambridge and stated that the C2 symmetry shown by Franklin's X-ray pictures was not used for building the structure, the realisation after the structure had been built that it had C2 symmetry helped confirm the correctness of the double helix as we know it. I wrote to Francis believing this to be incorrect (see 73 above); this is his reply (2003). 74. Letter from Odile Crick in which she gives her permission for me to place images of the papers I found of Crick's (which are now with the Churchill Archives) on the LMB web site (2006). I did not follow her suggestion that I add them to the Wellcome Collection as I believed they were legally mine. 75. Note to my father from Cockcroft on my degree (1961). 76. Article from a Swiss newspaper announcing that two Swiss had contributed to the Manhattan project in Los Alamos: the Staub and Bretscher families (I think 1947). * Excerpt of photo of 2 families. 77. Postcard from Crick to division (1964). 78. Note from Chadwick to E. and H. Bretscher. 79. Note from Chadwick to EB about my college fellowship. 80. Note from Chadwick to EB on MSB's 1st in Tripos I 1960. 81. Note from Ephraim Katchalski (later Israel's president) to me about some insoluble ribonuclease I wanted (which never came) 1963. 82. Letter from Fritz Lipmann following my publication of the structure of peptidyl-tRNA (1963) about how one of his post-docs did some (unpublished) work on this. 83. Invitation card to Francis and Odile studio party June 1st, 1962 (dig). 84. Notice for Francis's Nobel Prize party at Portugal Place, 1962 (dig). 85. Letter from Crick to MSB, 9.3.1961 (dig). 86. Note from Jim Ofengand with FHCC showing irritation at the manner Jim treated me, 1961 (dig). When I joined the unit, Francis was anxious that Jim Ofengand, a US postdoc, should show me the tricks required to get an in vitro protein synthesizing system to work: Jim was due to fly home in about 3 days. Jim promised to show me and, as the note indicates, he decided to do his on Sunday morning/evening. He then changed his mind as it was raining and did them Sunday afternoon. Francis came to the unit and noted his irritation with Jim's plans which were of little use to me. 87. 2 letters from Jim Rothman. . 88. Crick Memorial Meeting 2013. 89. International Police Force Organisation by Fred Sanger (1938). 90. Structures of amino acids and chemical doodles by FS, found in Sidgwick's 'Organic Chemistry' (1937). 91. Factor effecting absorption of a substance/drawing of a toad by FS. 92. Letter from Joan to FS dated 5 Jan 1939.
1 file.
43 Art book, by Fred Sanger. According to Mark Bretscher, Sanger also did several pastoral paintings in later life.
1 file.
c 1936
44 Slides.
1 file.

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