George Brownlee

Last updated

George Brownlee
Born
George Gow Brownlee

(1942-01-13) 13 January 1942 (age 82) [1]
Alma mater University of Cambridge (MA, PhD)
Spouse
Margaret Susan Kemp
​
(m. 1966)​
[1]
Awards
Scientific career
Fields Pathology
Institutions
Thesis Nucleotide sequences in the low molecular weight ribosomal ribonucleic acid of Escherichia coli  (1967)
Doctoral advisor Frederick Sanger [5] [6]
Doctoral students Greg Winter [7]
Website linc.ox.ac.uk/Fellows/GeorgeBrownlee

George Gow Brownlee is a British pathologist and Fellow of Lincoln College, Oxford. [8] [9] [10] [11] [12]

Contents

Education

Brownlee was educated at Dulwich College [1] and Emmanuel College, Cambridge where he studied Natural Sciences and was awarded a Master of Arts degree followed by PhD in 1967 for research on nucleotides supervised by Fred Sanger at the MRC Laboratory of Molecular Biology (LMB). [8] [13] [14]

Career and Research

Brownlee was Professor of Chemical Pathology at Sir William Dunn School of Pathology, from 1978 to 2008.[ citation needed ]

Brownlee cloned and expressed human clotting factor IX, [15] [16] providing a recombinant source of this protein for Haemophilia B patients who had previously relied on the hazardous blood-derived product.

With Merlin Crossley he helped discover the two sets of genetic mutations that were preventing two key proteins from attaching to the DNA of people with a rare and unusual form of Haemophilia B – Haemophilia B Leyden – where sufferers experience episodes of excessive bleeding in childhood but have few bleeding problems after puberty. This lack of protein attachment to the DNA was thereby turning off the gene that produces clotting factor IX, which prevents excessive bleeding. [17]

With Peter Palese and co-workers he developed the first reverse genetics system for influenza virus, markedly speeding up the process of developing influenza vaccines. [18]

Brownlee authored a biography of Fred Sanger published in 2014. [19] [20]

Awards and honours

Brownlee was awarded The Colworth Medal by the Biochemical Society in 1976 [2] and elected a Fellow of the Royal Society (FRS) in 1987. [1] His certificate of election and candidature reads:

Distinguished for his work on the sequences of nucleic acids and their biological implications. He contributed to the development of methods using 32P-labelling and two-dimensional fractionation techniques, which greatly accelerated the early RNA sequencing. He used these methods to determine the sequence of the 5S ribosomal RNA, at that time the largest nucleic acid to be sequenced. He used fingerprint analysis of messenger RNA to demonstrate that immunoglobulin V- and C-regions were not discontinuous at the messenger RNA level, and early analysis of messenger RNA to identify a precursor for light chain synthesis. Parallel studies on globin messenger RNA demonstrated important features of eucaryotic translation. More recently he has developed faster methods for RNA sequencing and has applied them to transfer RNAs and ovalbumin messenger RNA. He also studied the DNA sequence of the ovalbumin gene and its insertion sequences. He determined the nucleotide sequence of the multiple gene coding for the 5S RNA in Xenopus laevis and showed that the coding regions alternated with a repetitious region and a "pseudogene" that had a sequence homologous with part of the 5S region. [3]

Brownlee was also elected a Fellow of the Academy of Medical Sciences (FMedSci) in 1998 [1] [4] and an EMBO Member in 1979. [21]

See also

Related Research Articles

<span class="mw-page-title-main">Nucleic acid</span> Class of large biomolecules essential to all known life

Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). If the sugar is ribose, the polymer is RNA; if the sugar is deoxyribose, a variant of ribose, the polymer is DNA.

<span class="mw-page-title-main">Promoter (genetics)</span> Region of DNA encouraging transcription

In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of itself, such as tRNA or rRNA. Promoters are located near the transcription start sites of genes, upstream on the DNA . Promoters can be about 100–1000 base pairs long, the sequence of which is highly dependent on the gene and product of transcription, type or class of RNA polymerase recruited to the site, and species of organism.

<span class="mw-page-title-main">RNA</span> Family of large biological molecules

Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself or by forming a template for the production of proteins. RNA and deoxyribonucleic acid (DNA) are nucleic acids. The nucleic acids constitute one of the four major macromolecules essential for all known forms of life. RNA is assembled as a chain of nucleotides. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.

<span class="mw-page-title-main">Stop codon</span> Codon that marks the end of a protein-coding sequence

In molecular biology, a stop codon is a codon that signals the termination of the translation process of the current protein. Most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide chain, which may ultimately become a protein; stop codons signal the termination of this process by binding release factors, which cause the ribosomal subunits to disassociate, releasing the amino acid chain.

<span class="mw-page-title-main">Frederick Sanger</span> British biochemist (1918–2013)

Frederick Sanger was a British biochemist who received the Nobel Prize in Chemistry twice.

<span class="mw-page-title-main">Gene expression</span> Conversion of a genes sequence into a mature gene product or products

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, and ultimately affect a phenotype. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) and small nuclear RNA (snRNA), the product is a functional non-coding RNA. The process of gene expression is used by all known life—eukaryotes, prokaryotes, and utilized by viruses—to generate the macromolecular machinery for life.

<span class="mw-page-title-main">Haemophilia B</span> Genetic X-linked recessive bleeding disorder

Haemophilia B, also spelled hemophilia B, is a blood clotting disorder causing easy bruising and bleeding due to an inherited mutation of the gene for factor IX, and resulting in a deficiency of factor IX. It is less common than factor VIII deficiency.

<span class="mw-page-title-main">RNA polymerase</span> Enzyme that synthesizes RNA from DNA

In molecular biology, RNA polymerase, or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that catalyzes the chemical reactions that synthesize RNA from a DNA template.

Polyadenylation is the addition of a poly(A) tail to an RNA transcript, typically a messenger RNA (mRNA). The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In eukaryotes, polyadenylation is part of the process that produces mature mRNA for translation. In many bacteria, the poly(A) tail promotes degradation of the mRNA. It, therefore, forms part of the larger process of gene expression.

<span class="mw-page-title-main">Factor IX</span> Protein involved in coagulation

Factor IX, also known as Christmas factor, is one of the serine proteases involved in coagulation; it belongs to peptidase family S1. Deficiency of this protein causes haemophilia B.

<span class="mw-page-title-main">Ribosomal RNA</span> RNA component of the ribosome, essential for protein synthesis in all living organisms

Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal DNA (rDNA) and then bound to ribosomal proteins to form small and large ribosome subunits. rRNA is the physical and mechanical factor of the ribosome that forces transfer RNA (tRNA) and messenger RNA (mRNA) to process and translate the latter into proteins. Ribosomal RNA is the predominant form of RNA found in most cells; it makes up about 80% of cellular RNA despite never being translated into proteins itself. Ribosomes are composed of approximately 60% rRNA and 40% ribosomal proteins, though this ratio differs between prokaryotes and eukaryotes.

In eukaryote cells, RNA polymerase III is a protein that transcribes DNA to synthesize 5S ribosomal RNA, tRNA, and other small RNAs.

<span class="mw-page-title-main">Gene</span> Sequence of DNA that determines traits in an organism

In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and non-coding genes. During gene expression, DNA is first copied into RNA. RNA can be directly functional or be the intermediate template for the synthesis of a protein.

<span class="mw-page-title-main">Factor VIII (medication)</span> Pharmaceutical drug

Factor VIII is a medication used to treat and prevent bleeding in people with hemophilia A and other causes of low factor VIII. Certain preparations may also be used in those with von Willebrand's disease. It is given by slow injection into a vein.

<span class="mw-page-title-main">Biotechnology in pharmaceutical manufacturing</span>

Biotechnology is the use of living organisms to develop useful products. Biotechnology is often used in pharmaceutical manufacturing. Notable examples include the use of bacteria to produce things such as insulin or human growth hormone. Other examples include the use of transgenic pigs for the creation of hemoglobin in use of humans.

<span class="mw-page-title-main">Bacteriophage MS2</span> Species of virus

Bacteriophage MS2, commonly called MS2, is an icosahedral, positive-sense single-stranded RNA virus that infects the bacterium Escherichia coli and other members of the Enterobacteriaceae. MS2 is a member of a family of closely related bacterial viruses that includes bacteriophage f2, bacteriophage Qβ, R17, and GA.

<span class="mw-page-title-main">EEF1B2</span> Protein-coding gene in the species Homo sapiens

Elongation factor 1-beta is a protein that in humans is encoded by the EEF1B2 gene.

<span class="mw-page-title-main">CPSF4</span> Protein-coding gene in humans

Cleavage and polyadenylation specificity factor subunit 4 is a protein that in humans is encoded by the CPSF4 gene.

<span class="mw-page-title-main">Adolfo García-Sastre</span> Spanish and American academic

Adolfo García-Sastre,(born in Burgos, 10 October 1964) is a Spanish professor of Medicine and Microbiology and co-director of the Global Health & Emerging Pathogens Institute at the Icahn School of Medicine at Mount Sinai in New York City. His research into the biology of influenza viruses has been at the forefront of medical advances in epidemiology.

<span class="mw-page-title-main">Molecular cloning</span> Set of methods in molecular biology

Molecular cloning is a set of experimental methods in molecular biology that are used to assemble recombinant DNA molecules and to direct their replication within host organisms. The use of the word cloning refers to the fact that the method involves the replication of one molecule to produce a population of cells with identical DNA molecules. Molecular cloning generally uses DNA sequences from two different organisms: the species that is the source of the DNA to be cloned, and the species that will serve as the living host for replication of the recombinant DNA. Molecular cloning methods are central to many contemporary areas of modern biology and medicine.

References

  1. 1 2 3 4 5 "BROWNLEE, Prof. George Gow" . Who's Who . Vol. 2015 (online Oxford University Press  ed.). A & C Black.(Subscription or UK public library membership required.)
  2. 1 2 Brownlee, G. G. (1979). "The Fourteenth Colworth Medal Lecture Sequencing eukaryotic genes or the anatomy of DNA". Biochemical Society Transactions. 7 (2): 279–96. doi:10.1042/bst0070279. PMID   570938.
  3. 1 2 "Certificate of Election and Candidature: EC/1987/02 – George Gow Brownlee". London: Royal Society. Archived from the original on 27 August 2015. Retrieved 11 November 2013.
  4. 1 2 "Professor George Brownlee FRS FMedSci: Emeritus Professor of Chemical Pathology". London: Academy of Medical Sciences. Archived from the original on 27 August 2015.
  5. ↑ Brownlee, George G. (2015). "Frederick Sanger CBE CH OM. 13 August 1918 – 19 November 2013". Biographical Memoirs of Fellows of the Royal Society . 61: 437–466. doi: 10.1098/rsbm.2015.0013 . ISSN   0080-4606.
  6. ↑ "Oral History: Fred Sanger on George Brownlee". Cold Spring Harbor Laboratory. Archived from the original on 15 May 2015.
  7. ↑ "Greg Winter, PhD". academictree.org. Archived from the original on 30 December 2015.
  8. 1 2 "Professor George Brownlee, Lincoln College, Oxford". University of Oxford. Archived from the original on 18 December 2013.
  9. ↑ George Brownlee's publications indexed by the Scopus bibliographic database. (subscription required)
  10. ↑ Rao, Z.; Handford, P.; Mayhew, M.; Knott, V.; Brownlee, G. G.; Stuart, D. (1995). "The structure of a Ca(2+)-binding epidermal growth factor-like domain: Its role in protein-protein interactions". Cell. 82 (1): 131–141. doi: 10.1016/0092-8674(95)90059-4 . PMID   7606779.
  11. ↑ Caton, A. J.; Brownlee, G. G.; Yewdell, J. W.; Gerhard, W. (1982). "The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype)". Cell. 31 (2 Pt 1): 417–427. doi:10.1016/0092-8674(82)90135-0. PMID   6186384.
  12. ↑ Proudfoot, N. J.; Brownlee, G. G. (1976). "3′ Non-coding region sequences in eukaryotic messenger RNA". Nature. 263 (5574): 211–214. Bibcode:1976Natur.263..211P. doi:10.1038/263211a0. PMID   822353.
  13. ↑ Brownlee, George Gow (1967). Nucleotide sequences in the low molecular weight ribosomal ribonucleic acid of Escherichia coli (PhD thesis). University of Cambridge. ProQuest   301246027.
  14. ↑ Brownlee, George C. (2014). "Fred Sanger, Double Nobel Laureate: A Biography". RNA . 22 (3): 317. doi:10.1261/rna.055590.115. PMC   4748809 .
  15. ↑ Choo, K. H.; Gould, K. G.; Rees, D. J. G.; Brownlee, G. G. (1982). "Molecular cloning of the gene for human anti-haemophilic factor IX". Nature. 299 (5879): 178–180. Bibcode:1982Natur.299..178C. doi:10.1038/299178a0. PMID   6287289.
  16. ↑ Anson, D. S.; Austen, D. E. G.; Brownlee, G. G. (1985). "Expression of active human clotting factor IX from recombinant DNA clones in mammalian cells". Nature. 315 (6021): 683–685. Bibcode:1985Natur.315..683A. doi:10.1038/315683a0. PMID   2989700.
  17. ↑ Crossley, M; Brownlee, G. G. (1990). "Disruption of a C/EBP binding site in the factor IX promoter is associated with haemophilia B". Nature. 345 (6274): 444–6. Bibcode:1990Natur.345..444C. doi:10.1038/345444a0. PMID   2342576.
  18. ↑ Fodor, E.; Devenish, L.; Engelhardt, O. G.; Palese, P.; Brownlee, G. G.; García-Sastre, A. (1 November 1999). "Rescue of influenza A virus from recombinant DNA". Journal of Virology. 73 (11): 9679–9682. doi:10.1128/JVI.73.11.9679-9682.1999. ISSN   0022-538X. PMC   113010 . PMID   10516084.
  19. ↑ "Fred Sanger, Double Nobel Laureate: A Biography". Cambridge University Press . Retrieved 22 August 2014. ISBN   1107083346
  20. ↑ "Biography celebrates life of Fred Sanger". St. John's College, Cambridge.
  21. ↑ "EMBO Profile: George G. Brownlee". people.embo.org. Heidelberg: European Molecular Biology Organization.
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