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 (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 Lemberg Medal in 1988 [24] and the Macfarlane Burnet Medal and Lecture in 1995. [25]
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 a 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:
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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.
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.
In structural biology, a beta-propeller (β-propeller) is a type of all-β protein architecture characterized by 4 to 8 highly symmetrical blade-shaped beta sheets arranged toroidally around a central axis. Together the beta-sheets form a funnel-like active site.
In virology, a spike protein or peplomer protein is a protein that forms a large structure known as a spike or peplomer projecting from the surface of an enveloped virus. The proteins are usually glycoproteins that form dimers or trimers.
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. Viral neuraminidase was discovered by Alfred Gottschalk at the Walter and Eliza Hall Institute in 1957. Neuraminidase inhibitors are antiviral agents that inhibit influenza viral neuraminidase activity and are of major importance in the control of influenza.
Hemagglutinins are homotrimeric glycoproteins present on the protein capsids of viruses in the Paramyxoviridae and Orthomyxoviridae families. Hemagglutinins are responsible for binding to receptors, sialic acid residues, on host cell membranes to initiate virus docking and infection.
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.
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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 would be a flu vaccine effective against all human-adapted strains of influenza A and influenza B regardless of the virus sub type, or any antigenic drift or antigenic shift. Hence it should not require modification from year to year in order to keep up with changes in the influenza virus. As of 2024 no universal flu vaccine had been successfully developed, however several candidate vaccines were in development, with some undergoing early stage clinical trial.
Gary J. Nabel is an American virologist and immunologist who is President and chief executive officer of ModeX Therapeutics in Natick, Massachusetts. He was the founding director of Vaccine Research Center at the National Institute of Allergy and Infectious Diseases.
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