George Brownlee | |
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Born | George Gow Brownlee 13 January 1942 [1] |
Alma mater | University of Cambridge (MA, PhD) |
Spouse | Margaret Susan Kemp (m. 1966) |
Awards |
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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 |
George Gow Brownlee is a British pathologist and Fellow of Lincoln College, Oxford. [8] [9] [10] [11] [12]
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]
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]
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]
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.
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.
Frederick Sanger was a British biochemist who received the Nobel Prize in Chemistry twice.
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.
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.
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.
A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and viruses.
Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products. Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network.
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.
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.
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.
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.
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.
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.
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.
Eukaryotic transcription is the elaborate process that eukaryotic cells use to copy genetic information stored in DNA into units of transportable complementary RNA replica. Gene transcription occurs in both eukaryotic and prokaryotic cells. Unlike prokaryotic RNA polymerase that initiates the transcription of all different types of RNA, RNA polymerase in eukaryotes comes in three variations, each translating a different type of gene. A eukaryotic cell has a nucleus that separates the processes of transcription and translation. Eukaryotic transcription occurs within the nucleus where DNA is packaged into nucleosomes and higher order chromatin structures. The complexity of the eukaryotic genome necessitates a great variety and complexity of gene expression control.
Elongation factor 1-beta is a protein that in humans is encoded by the EEF1B2 gene.
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.
Ervin Fodor is a British virologist of Hungarian origin born in Czechoslovakia. He is Professor of Virology holding the position of reader in experimental pathology in the Sir William Dunn School of Pathology at the University of Oxford. He is also a professorial fellow at Exeter College, Oxford.