Research notebooks of Professor George Brownlee

Bodleian Library, University of Oxford

Charlotte McKillop-Mash
2017



Department of Special Collections
Contact Information
Search Online Catalogues


Table of Contents

Introduction
A   Medical Research Council notes 1971-1972
B   Dunn School notebooks, 1980-1988 Oct 1980-May 1988
C   Australian sabbatical visit, 1986-1987 Aug 1986-Jul 1987
D   Dunn School notebooks, 1988-2008 May 1988-Sep 2008
E   Assistants notebooks 1981, 1993–1997


Research notebooks of Professor George Brownlee and his assistants

1971-2008

Abstract:
Laboratory notebooks of Professor George Brownlee, the E.P. Abraham Professor of Chemical Pathology at the Sir William Dunn School of Pathology, University of Oxford.

Extent: 4 Linear meters, 28 physical shelfmarks
Language(s) of Material: English

Biographical/Historical

Professor George Gow Brownlee, FMedSci, FRS, was born in 1942 and took his degree and then a PhD at Emmanuel College Cambridge, studying under double Nobel Laureate Dr. Fred Sanger at the Laboratory of Molecular Biology. He worked for the Medical Research Council in Cambridge from 1966 until 1980 and then came to Oxford as a Fellow of Lincoln College and the first holder of the E.P. Abraham Professor of Chemical Pathology chair at the Sir William Dunn School of Pathology, which he held until retirement in 2008. In 1987, he was elected a Fellow of the Royal Society, and was a founding fellow of the Academy of Medical Sciences in 1998. He is a trustee and former chair of the University of Oxford's EP Abraham Cephalosporin Fund.

Professor Brownlee's research interests were in molecular biology, and he and his group made significant discoveries in sequencing RNA and DNA during the early days of that field of research, starting in the 1960s when he contributed to the development of RNA sequencing methods, and used them to determine the sequence of the 5S ribosomal RNA, which was at that time the longest nucleic acid to have been sequenced. In 1977, his group discovered the existence of pseudogenes - abnormal, mutated genes - which are now known to be ubiquitous in the genome of all organisms. After 1980, Brownlee became more involved in applied medical problems, and succeeded in isolating the clotting factor IX gene, present in people with haemophilia B. This led to improved treatment. He went on to work on gene regulation in the influenza virus. In 1999 Brownlee and Ervin Fodor sequenced the RNA genome of influenza. This allowed them to isolate recombinant influenza virus in cell culture, which led to improved vaccines for children.

Scope and Content

Comprises 28 research notebooks covering experiments carried out by Brownlee, his students and assistants, particularly during his time at the Sir William Dunn School of Pathology of the University of Oxford, 1980-2008.

The descriptions of the notebooks were compiled by Professor George Brownlee, 1971-2008. His original descriptions are also provided in each box.

Acquisition

Donated by Professor George Brownlee, Jan 2017.

Origination

Brownlee | George Gow | Professor | 1942- | chemical pathologist

MSS. 12364/1-28

Preferred Form of Citation

Oxford, Bodleian Library, MS. 12364/1

Subject(s)

Academic writing
Science
Sir William Dunn School of Pathology

A   Medical Research Council notes 1971-1972

Scope and Content

Between 1963-1980 Brownlee worked at the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, first as PhD student supervised by Fred Sanger and then as an independent, MRC-supported research worker with his own PhD students, and a small research team within Fred Sanger’s division. Brownlee discarded all his research notebooks from this period, except for one notebook describing the research leading up to his team's Nature letter (Milstein, Brownlee, Harrison & Matthews (1972) Nature, New Biology, 239,117-120).

Full range of shelfmarks:

MS. 12364/1


Medical Research Council notes
Date: 1971-1972
Shelfmark: MS. 12364/1
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Medical Research Council notes, labelled 'Book 4/P3' - P3 refers to Potter tumour 3, Jun 1971-1972:

B   Dunn School notebooks, 1980-1988 Oct 1980-May 1988

Scope and Content

The following notebooks cover the period where Brownlee held the position of E.P. Abraham Professor of Chemical Pathology in the Sir William Dunn School of Pathology at the University of Oxford, Oct 1980 to Sep 2008. Moving from the Laboratory of Molecular Biology, Cambridge in Oct 1980, Brownlee transferred his influenza research project. In addition he started a new line of research on the genetic basis of haemophilia B. The 23 Dunn School notebooks cover this research. An additional two notebooks (Australian notebooks 1 and 2) cover Brownlee's research sabbatical in Melbourne, Australia in 1986-1987 and have been inserted chronologically between Dunn School Notebooks 6 and 7.

During this period, Brownlee directed three research assistants: Joyce Huddleston; Vroni Knott and Jane Sharps.

Full range of shelfmarks:

MSS. 12364/2-7


Dunn School: Notebook 1
Date: Oct 1980-Dec 1982
Shelfmark: MS. 12364/2
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Notebook 1, opens with a three page index (table of contents).

This notebook starts with experiments number 1 & 2 on the influenza virus (strain A/NT60/68) in which Bernie Moss and Brownlee were characterizing a DI band (referred to as band 9) by Maxam Gilbert sequencing. Brownlee then moved on to factor IX experiments attempting to sequence the DNA products synthesized by reverse transcriptase from a predicted factor IX oligonucleotide primer (experiment numbers 3-8) and bovine liver mRNA (prepared by Andy Choo, a post-doctoral researcher from Melbourne, Australia). These experiments failed to show any possible factor IX synthetic DNA.

Further experiments relate to the cloning and sequencing of the nucleoprotein band 5 of influenza A/NT/60/68 RNA. Other experiments relate to bands 1-3 of influenza virus A/NT60/68. In particular Brownlee was trying to construct libraries of sonicated or enzyme-restricted ds DNA in m13 phage vectors for Sanger dideoxy sequencing. Construction of new plasmid vector (modified from pAT153) for blunt-ended cloning. New plasmid named pAT153/Pvu II/8 (experiments 55-56). Data sheet prepared, 2 Mar 1982 (see experiment 57, page 119).

In experiments 78-79 and following, e.g. experiment 105, Brownlee attempted cloning of a library of cDNA of polyA+ bovine liver cDNA (in order to isolate factor IX clones) using various enzymatic methods to generate dsDNA and various plasmid cloning vectors. Some clones isolated but inefficient. (See the loose leaf inserted on p. 247- in Andy Choo’s hand – showing batches of polyA+ bovine liver RNA he had prepared - including a purified sucrose gradient fraction. Near the end of the notebook (pages unnumbered) see incomplete notes on a meeting with Dr MP Esnouv on 27 Nov 1980 at the Radcliffe Infirmary. It was at this meeting that Brownlee became aware of Esnouv's work sequencing bovine factor IX. This suggested the approach of first isolating a clone of bovine factor IX since bovine liver was easier to come by than a human liver. Esnouv gave Brownlee some antibodies and bovine factor IX and suggested Brownlee contact Dr Luther at ARC Compton to obtain some calf liver.

Experiment 91 (page 201) concerns a design of a cloning strategy for expression of the influenza haemagglutinin containing clone in mouse fibroblasts.

Dunn School: Notebook 2
Date: Dec 1982-Oct 1983
Shelfmark: MS. 12364/3
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Notebook covers experiments including:

Restrictions on Access:

Closed.


Dunn School: Notebook 3
Date: Oct 1983-Jul 1984
Shelfmark: MS. 12364/4
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Notebook covers experiments including:

Restrictions on Access:

Closed.


Dunn School: Notebook 4
Date: Jul 1984-May 1985
Shelfmark: MS. 12364/5
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Notebook covers experiments including:

Dunn School: Notebook 5
Date: May 1985-Jul 1986
Shelfmark: MS. 12364/6
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Notebook covers experiments including:

Dunn School: Notebook 6
Date: Jul 1986-May 1988
Shelfmark: MS. 12364/7
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Covers experiments 458-469, then the numbering of experiments restarts from number 1 on return from a sabbatical in Melbourne in Aug 1987 (see separate Australian sabbatical notebooks 1 and 2 below).

This notebook covers two independent topics:

1. Finishing off the E coli cosmid mapping and relating the work to a published Cell paper (1986) by Kohara et al (Japan) 2. Starting gene therapy work by ex vivo infection of cells and tissues followed by skin grafting in BALB/C mice

C   Australian sabbatical visit, 1986-1987 Aug 1986-Jul 1987

Scope and Content

The following notebooks cover Brownlee's sabbatical at the Murdoch Institute, Childrens' Hospital Melbourne, (courtesy of the Director, David Danks) and then at the Walter and Eliza Hall, Institute of Medical Research, Melbourne, courtesy of Ken Shortman and Gus Nossal, Director.

Full range of shelfmarks:

MSS. 12364/8-9


Australian sabbatical visit: Notebook 1
Date: Aug 1986-Feb 1987
Shelfmark: MS. 12364/8
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Brownlee was attempting to set up an assay to detect point mutations in DNA by forming DNA- 32P RNA heteroduplexes and subsequently detecting Watson-Crick mismatches with RNases. He was helped by Andy Choo at the host laboratory. Choo provided Brownlee with DNA of different individuals (experiment 3). Brownlee intended to probe for RFLPs in the factor IX gene, following up work of Peter Winship in Brownlee's lab in Oxford. Mismatches had been detected before in other genes (see experiment 4, Myers et al. 1985) but Brownlee hoped to improve on Myers by using other RNases or different conditions of RNase digestion.

Australian sabbatical visit: Notebook 2
Date: Feb 1987-Jul 1987
Shelfmark: MS. 12364/9
Language(s) of Material: English
Extent: 1 volume

Scope and Content

This was a continuation of Brownlee's sabbatical at the Murdoch Institute, Childrens' Hospital Melbourne, and then from 30 Mar 1987 at the Walter and Eliza Hall, Institute of Medical Research, Melbourne.

Brownlee continued (Topic 1) with Ruth Brown, to try and isolate cosmids that had both human and mouse DNA repetitive sequences, thus potentially marking the translocation between human and mouse sequences in her somatic cell hybrid. He also continued (Topic 2) experiments trying to use RNases to detect base-pair mismatches in DNA-RNA heteroduplexes.

George Brownlee states: "These experiments, using the Indium CTL assay, seemed not well designed. There was no clear hypothesis. Rather I was learning, first hand, how to do various assays which were new to me. No publishable results":

D   Dunn School notebooks, 1988-2008 May 1988-Sep 2008

Full range of shelfmarks:

MSS. 12364/10-26


Dunn School: Notebook 7
Date: May 1988 – Apr 1989
Shelfmark: MS. 12364/10
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Mainly gene therapy experiments; also proposed homologous gene targetting experiments (scheme p. 147):

Dunn School: Notebook 8
Date: Apr 1989–Dec 1991
Shelfmark: MS. 12364/11
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Experiments with radioiodinated T cell epitope peptides (KGoul 2 and 4) and their properties binding to BALB/c and CBA-derived mouse liver microsomes - to test if there is any specificity. Essentially a collaboration with Keith Gould (a post-doctoral researcher) who had characterized several peptide epitopes in the influenza HA and NP proteins, (experiments 124, 126, 149A, 160 with DPhil student Judy Cossins, etc.). Binding and cross-linking experiments. Unsuccessful, as uninterpretable.

Experiments grafting keratinocytes onto skin of mice (experiments 136, 141; 145, 163 both mention DPhil student Ann Gerrard). Aiming to test gene therapy in a human skin-grafted nude mouse model (collaboration with Fiona Watt (ICRF London)). She supplied the human skin cells, the Brownlee lab did the infection and grafting in mice. Experiment 141 mentions Mr. [Jim] Kent - the animal house assistant who helped with the famous penicillin experiments with Norman Heatley in 1939-1940.

Dunn School: Notebook 9
Date: Jan 1991–May 1992
Shelfmark: MS. 12364/12
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Notebook covers experiments including:

Dunn School: Notebook 10
Date: May 1992-Sep 1993
Shelfmark: MS. 12364/13
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Many different experiments including:

Dunn School: Notebook 11
Date: Sep 1993–Aug 1994
Shelfmark: MS. 12364/14
Language(s) of Material: English
Extent: 1 volume

Scope and Content

All experiments relate to influenza virus - particularly to the vRNA promoter (experiments 308, 309 etc.) and its binding to MN cores, to baculovirus-expressed PB1 and Baculovirus-expressed PB2 (with Ervin Fodor). Brownlee and Fodor designed a "tied panhandle" i.e. oligo 134 for vRNA and oligo 135 for cRNA (experiments 308, 309). They also compared results with a "perfect duplex" of the vRNA promoter.

These experiments depended on the synthesis of RNA, in house, by Keith Gould.

Includes:

Dunn School: Notebook 12
Date: Aug 1994-Oct 1994
Shelfmark: MS. 12364/15
Language(s) of Material: English
Extent: 1 volume

Scope and Content

All experiments are influenza related. George Brownlee states: "On the whole a very successful set of experiments using in-house synthesized RNA (by Keith Gould)":

Dunn School: Notebook 13
Date: Oct 1994–Dec 1995
Shelfmark: MS. 12364/16
Language(s) of Material: English
Extent: 1 volume

Scope and Content

[George Brownlee's son, Edward George Brownlee, died in December 1995 of a brain haemorrhage. See the draft of the obituary for The Times and the Hull Daily Mail at the end of this Notebook and various other notes relating to his death.]

A series of experiments setting up an RT-PCR assay for detecting a full length cRNA transcript of a synthetic 50-mer (tied vRNA panhandle) and MN-cores. Also RT-PCR for polyadenylated transcripts. Both assays were ultimately successful, although unpublished (see below). They provided the basis for further work by David Pritlove and Leo Poon which was published later.

Dunn School: Notebook 14
Date: Mar 1996-Apr 1999
Shelfmark: MS. 12364/17
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Notebook covers experiments including:

Dunn School: Notebook 15
Date: Apr 1999- Feb 2000
Shelfmark: MS. 12364/18
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Influenza-related experiments:

Dunn School: Notebook 16
Date: Feb 2000-Nov 2000
Shelfmark: MS. 12364/19
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Influenza related experiments:

Dunn School: Notebook 17
Date: Nov 2000-Jul 2001
Shelfmark: MS. 12364/20
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Notebook covers experiments including:

Dunn School: Notebook 18
Date: Aug 2001-Jan 2003
Shelfmark: MS. 12364/21
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Notebook covers experiments including:

Dunn School: Notebook 19
Date: Jan 2003-Jul 2004
Shelfmark: MS. 12364/22
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Restarts the numbering of experiments at number 1:

Dunn School: Notebook 20
Date: Jul 2004-May 2006
Shelfmark: MS. 12364/23
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Notebook covers experiments including:

Dunn School: Notebook 21
Date: May 2006–Feb 2007
Shelfmark: MS. 12364/24
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Notebook covers experiments including:

Dunn School: Notebook 22
Date: Feb 2007-Feb 2008
Shelfmark: MS. 12364/25
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Notebook covers experiments including:

Dunn School: Notebook 23
Date: Feb 2008-Sep 2008
Shelfmark: MS. 12364/26
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Brownlee retired on 30 Sep 2008. This box includes his curriculum vitae and publications list and a notebook which covers experiments including:

E   Assistants notebooks 1981, 1993–1997

Full range of shelfmarks

MSS. 12364/27-28


Notebook of Joyce Huddleston
Date: Jan 1981-Jun 1981
Shelfmark: MS. 12364/27
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Huddleston's other 4[?] notebooks were (as Brownlee states) unfortunately discarded when she retired in 2008.

Huddleston was Brownlee's research assistant from early 1981, having previously been assistant to Sir Edward Abraham. Brownlee states: "I had to teach her molecular biology. She taught me to keep a better lab notebook."

Ringbook of Jane Sharps
Date: 1993–1997
Shelfmark: MS. 12364/28
Language(s) of Material: English
Extent: 1 volume

Scope and Content

Jane Sharps, on Sir Henry Harris' retirement, joined Brownlee as a research assistant working with him, except for a short gap, until shortly before Brownlee's retirement in 2008. This is a summary of her first ringbook working with Brownlee. Her remaining notebooks are still in her keeping and are a useful resource, while she continues as Professor Ervin Fodor's assistant.


Transformation from XML (EAD 2.0) to HTML
05 October 2017