Peter Colman | |
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Born | Peter Malcolm Colman 3 April 1944 [1] |
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Thesis | The physical structure of two parabanic acid complexes and an investigation of short intermolecular carbon-oxygen contacts (1969) |
Doctoral advisor | Harry Medlin [6] |
Website | www |
Peter Malcolm Colman AC FRS FAA FTSE (born 1944) [1] is the head of the structural biology division at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia. [7]
Colman was educated at the University of Adelaide, where he received a Bachelor of Science degree in physics in 1966 [1] and a PhD in 1969 for research on the chemical structure of parabanic acid complexes supervised by Harry Medlin. [6]
Colman's research interests are in structural biology, [8] [9] [10] especially of human B-cell lymphoma 2 (BCL-2). [11] [12] [13] [14] Colman determined the three-dimensional structure of the influenza virus neuraminidase and, in one of the earliest cases of structure-based drug design, discovered zanamivir, the first-in-class neuraminidase inhibitor for influenza. [15] His subsequent structural studies on resistance to this drug class suggested how to design drugs against moving targets. [15] His discoveries underpin drug stockpiling for pandemic preparedness. [15] He has made seminal contributions to structural studies of antibodies and antibody-antigen complexes. [15] Recent[ when? ] work on apoptosis solves the long-standing problem of how pro-apoptotic Bax changes conformation to dimerise and then oligomerise and permeabilise the mitochondrial membrane, an essential step in the intrinsic cell-death pathway. [15]
His work has been published in leading peer reviewed scientific journals including Nature , [8] [16] [17] [18] [19] [20] the Journal of Molecular Biology , [21] and Nature Reviews Molecular Cell Biology . [22]
In the Queen's 2017 Birthday Honours Colman was appointed a Companion of the Order of Australia (AC), Australia's highest civilian honour, "for eminent service to medical research, particularly in the fields of structural biology and medicinal chemistry, as a leader in the commercial translation of scientific discoveries, to professional organisations, and as a mentor of young scientists". [23]
Colman was elected a Fellow of the Royal Society (FRS) in 2014. [15] In 2001 he was awarded a Centenary Medal "For service to Australian society and science in structural biology". [5] Colman was also elected a Fellow of the Australian Academy of Science in 1989 and a Fellow of the Australian Academy of Technological Sciences and Engineering in 1997. [1] He was awarded the Macfarlane Burnet Medal and Lecture in 1995. [24]
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.
Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains. The term is often applied specifically to influenza, as that is the best-known example, but the process is also known to occur with other viruses, such as visna virus in sheep. Antigenic shift is a specific case of reassortment or viral shift that confers a phenotypic change.
Influenza hemagglutinin (HA) or haemagglutinin[p] is a homotrimeric glycoprotein found on the surface of influenza viruses and is integral to its infectivity.
Antigenic drift is a kind of genetic variation in viruses, arising from the accumulation of mutations in the virus genes that code for virus-surface proteins that host antibodies recognize. This results in a new strain of virus particles that is not effectively inhibited by the antibodies that prevented infection by previous strains. This makes it easier for the changed virus to spread throughout a partially immune population. Antigenic drift occurs in both influenza A and influenza B viruses.
Zanamivir is a medication used to treat and prevent influenza caused by influenza A and influenza B viruses. It is a neuraminidase inhibitor and was developed by the Australian biotech firm Biota Holdings. It was licensed to Glaxo in 1990 and approved in the US in 1999, only for use as a treatment for influenza. In 2006, it was approved for prevention of influenza A and B. Zanamivir was the first neuraminidase inhibitor commercially developed. It is marketed by GlaxoSmithKline under the trade name Relenza as a powder for oral inhalation.
Exo-α-sialidase is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids:
Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural proteins, which can then self assemble into the virus-like structure. Combinations of structural capsid proteins from different viruses can be used to create recombinant VLPs. Both in-vivo assembly and in-vitro assembly have been successfully shown to form virus-like particles. VLPs derived from the Hepatitis B virus (HBV) and composed of the small HBV derived surface antigen (HBsAg) were described in 1968 from patient sera. VLPs have been produced from components of a wide variety of virus families including Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages. VLPs can be produced in multiple cell culture systems including bacteria, mammalian cell lines, insect cell lines, yeast and plant cells.
Sir Gregory Paul Winter is a Nobel Prize-winning English molecular biologist best known for his work on the therapeutic use of monoclonal antibodies. His research career has been based almost entirely at the MRC Laboratory of Molecular Biology and the MRC Centre for Protein Engineering, in Cambridge, England.
Nucleoproteins are proteins conjugated with nucleic acids. Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins.
Neuraminidase inhibitors (NAIs) are a class of drugs which block the neuraminidase enzyme. They are a commonly used antiviral drug type against influenza. Viral neuraminidases are essential for influenza reproduction, facilitating viral budding from the host cell. Oseltamivir (Tamiflu), zanamivir (Relenza), laninamivir (Inavir), and peramivir belong to this class. Unlike the M2 inhibitors, which work only against the influenza A virus, NAIs act against both influenza A and influenza B.
Enterovirus E is a picornavirus of the genus Enterovirus. The virus may also be referred to as enteric cytopathic bovine orphan virus (ECBO). It is endemic in cattle populations worldwide, and although normally fairly nonpathogenic, it can cause reproductive, respiratory, or enteric disease – particularly when the animal is concurrently infected with another pathogen.
Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell. Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins. Neuraminidase inhibitors are antiviral agents that inhibit influenza viral neuraminidase activity and are of major importance in the control of influenza.
In molecular biology, hemagglutinins are receptor-binding membrane fusion glycoproteins produced by viruses in the Paramyxoviridae family. Hemagglutinins are responsible for binding to receptors on red blood cells to initiate viral attachment and infection. The agglutination of red cells occurs when antibodies on one cell bind to those on others, causing amorphous aggregates of clumped cells.
Hemagglutinin-neuraminidase refers to a single viral protein that has both hemagglutinin and (endo) neuraminidase EC 3.2.1.18 activity. This is in contrast to the proteins found in influenza, where both functions exist but in two separate proteins. Its neuraminidase domain has the CAZy designation glycoside hydrolase family 83 (GH83).
A heavy-chain antibody is an antibody which consists only of two heavy chains and lacks the two light chains usually found in antibodies.
Peter Palese is a United States microbiologist, researcher, inventor and the Horace W. Goldsmith Professor in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai in New York City, and an expert in the field of RNA viruses.
George Keble Hirst, M.D. was an American virologist and science administrator who was among the first to study the molecular biology and genetics of animal viruses, especially influenza virus. He directed the Public Health Research Institute in New York City (1956–1981), and was also the founding editor-in-chief of Virology, the first English-language journal to focus on viruses. He is particularly known for inventing the hemagglutination assay, a simple method for quantifying viruses, and adapting it into the hemagglutination inhibition assay, which measures virus-specific antibodies in serum. He was the first to discover that viruses can contain enzymes, and the first to propose that virus genomes can consist of discontinuous segments. The New York Times described him as "a pioneer in molecular virology."
Neuraminidase inhibitors inhibit enzymatic activity of the enzyme neuraminidase (sialidase). These type of inhibitors have been introduced as anti-influenza drugs as they prevent the virus from exiting infected cells and thus stop further spreading of the virus. Neuraminidase inhibitors for human neuraminidase (hNEU) have the potential to be useful drugs as the enzyme plays a role in several signaling pathways in cells and is implicated in diseases such as diabetes and cancer.
A universal flu vaccine is a flu vaccine that is effective against all influenza strains regardless of the virus sub type, antigenic drift or antigenic shift. Hence it should not require modification from year to year. As of 2021 no universal flu vaccine had been approved for general use, several were in development, and one was in clinical trial.
Influenza D virus is a species in the virus genus Deltainfluenzavirus, in the family Orthomyxoviridae, that causes influenza.
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