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 FRS FMedSci 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.
Frederick Sanger was an English biochemist who received the Nobel Prize in Chemistry twice.
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called non-coding RNAs (ncRNAs). mRNA comprises only 1–3% of total RNA samples. Less than 2% of the human genome can be transcribed into mRNA, while at least 80% of mammalian genomic DNA can be actively transcribed, with the majority of this 80% considered to be ncRNA.
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.
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.
Factor IX is one of the serine proteases of the coagulation system; it belongs to peptidase family S1. Deficiency of this protein causes haemophilia B. It was discovered in 1952 after a young boy named Stephen Christmas was found to be lacking this exact factor, leading to haemophilia.
In eukaryote cells, RNA polymerase III is a protein that transcribes DNA to synthesize 5S ribosomal RNA, tRNA and other small RNAs.
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.
The Argonaute protein family, first discovered for its evolutionarily conserved stem cell function, plays a central role in RNA silencing processes as essential components of the RNA-induced silencing complex (RISC). RISC is responsible for the gene silencing phenomenon known as RNA interference (RNAi). Argonaute proteins bind different classes of small non-coding RNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). Small RNAs guide Argonaute proteins to their specific targets through sequence complementarity, which then leads to mRNA cleavage, translation inhibition, and/or the initiation of mRNA decay.
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.
The 5S ribosomal RNA is an approximately 120 nucleotide-long ribosomal RNA molecule with a mass of 40 kDa. It is a structural and functional component of the large subunit of the ribosome in all domains of life, with the exception of mitochondrial ribosomes of fungi and animals. The designation 5S refers to the molecule's sedimentation velocity in an ultracentrifuge, which is measured in Svedberg units (S).
Elongation factor 1-beta is a protein that in humans is encoded by the EEF1B2 gene.
Cleavage and polyadenylation specificity factor subunit 5 (CPSF5) is an enzyme that in humans is encoded by the NUDT21 gene. It belongs to the Nudix family of hydrolases.
General transcription factor IIH subunit 2 is a protein that in humans is encoded by the GTF2H2 gene.
Cleavage and polyadenylation specificity factor subunit 4 is a protein that in humans is encoded by the CPSF4 gene.
Stanley Fields is an American biologist best known for developing the yeast two hybrid method for identifying protein–protein interactions. He is currently a professor of Genome Sciences at the University of Washington and Howard Hughes Medical Institute Investigator, and serves as chair of the Department of Genome Sciences.
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.
Moroctocog alfa is a recombinant antihemophilic factor genetically engineered from Chinese hamster ovary (CHO) cell line. Chemically it is a glycoprotein. It is manufactured by Genetics Institute, Inc. and used to control and prevent hemorrhagic bleeding and prophylaxis associated with surgery or to reduce the number of spontaneous bleeding episodes in patients with hemophilia A. It is partially a recombinant coagulation factor VIII since it has an amino acid sequence which compares to the 90 + 80 kDa form of factor VIII (BDDrFVIII). It also has posttranslational modifications which are similar to those of the plasma-derived molecule. It can not prevent hemorrhagic bleeding associated with von Willebrand's disease since it is not a von Willebrand factor.
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.
Sir Hugh Reginald Brentnall Pelham, is a cell biologist who has contributed to our understanding of the body's response to rises in temperature through the synthesis of heat shock proteins. He served as director of the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) between 2006 and 2018.