A major contributor to this article appears to have a close connection with its subject.(July 2018) |
Robert E. W. Hancock | |
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Born | March 23, 1949 |
Nationality | Canadian |
Occupation | Professor |
Awards | Officer of the Order of Canada, ICAAC Antimicrobial Research Award, Prix Galien, Order of British Columbia |
Academic background | |
Alma mater | University of Adelaide |
Academic work | |
Discipline | Microbiology and Immunology |
Institutions | University of British Columbia |
Notable ideas | Self-promoted uptake theory,Cationic peptides as immune modulators |
Website | Hancock Lab Website |
Robert Ernest William Hancock OC OBC FRSC (born March 23,1949) is a Canadian microbiologist and University of British Columbia Killam Professor of Microbiology and Immunology,an Associate Faculty Member of the Wellcome Trust Sanger Institute,and a Canada Research Chair in Health and Genomics.
Over his career he has published more than 800 papers and reviews,has 72 patents awarded,and is an ISI highly cited author in Microbiology with more than 113,000 citations and an h-index of 168. He has won several awards and is an Officer of the Order of Canada. He is a co-founder of Migenix,Inimex Pharmaceuticals,ABT Innovations,Sepset Biotherapeutics,and the Centre for Drug Research and Development. He serves as a member of the Scientific Advisory Board for Qu Biologics. [1]
Hancock received his BSc (First Class Honors) (1971) and PhD (1975) in Microbiology from the University of Adelaide,where he studied bacteriophage receptors. [2] He did his post-doctoral work at the University of Tübingen in Germany (1975-1977),where he studied the E. coli outer membrane,followed by a research year at the University of California,Berkeley. At Berkeley,he began his work on Pseudomonas aeruginosa and porins proteins that form channels in membranes. While at UBC he came up with the self-promoted uptake theory, [3] the idea that antibiotics promote their own uptake across the cell membrane.
Hancock began studying antibiotic resistance mechanisms in Pseudomonas aeruginosa,which eventually led to his involvement in sequencing the genome of Pseudomonas,only the 4th bacterial genome to be sequenced. [4] Hancock's research identified new mechanisms of antibiotic resistance especially dependent on lifestyle adaptations in Pseudomonas, [5] and found new therapeutics for treating antibiotic resistant pathogens. [6] [7] This then led to investigating small cationic peptides from nature,originally termed cationic antimicrobial peptides, [5] but eventually "host defence peptides". Hancock became one of the first and most prominent advocates that the major function of these peptides was as modulators of the immune system. [7] [8] To understand the role of these peptides as modulators of the immune system he developed InnateDB,NetworkAnalyst and MetaBridge as tools to enable systems/network biology studies and insights. [9]
Currently Hancock and his lab’s research interests include small cationic peptides as novel antimicrobials,broad-spectrum anti-biofilm agents,and modulators of innate immunity,the development of novel treatments for antibiotic resistant infections and inflammation,the systems biology of innate immunity,inflammatory diseases and Pseudomonas aeruginosa,and antibiotic uptake and resistance.
Hancock and Gerry Wright formed the Canadian Anti-infective Innovation Network (CAIN) in 2017. CAIN was formed with the purpose of leveraging innovative approaches and expertise to solve the expanding health crisis caused by Antimicrobial Resistance (AMR) infections. In less than a year CAIN grew to over 90 members from across Canada.
Hancock is the director of the Centre for Microbial Diseases and Immunity Research (CMDR) a multi-faculty,multi-department consortium of world class microbial diseases and immunology researchers located at the University of British Columbia.
Hancock co-founded the following companies:
A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular polymeric substances (EPSs). The cells within the biofilm produce the EPS components, which are typically a polymeric conglomeration of extracellular polysaccharides, proteins, lipids and DNA. Because they have three-dimensional structure and represent a community lifestyle for microorganisms, they have been metaphorically described as "cities for microbes".
Bacteriocins are proteinaceous or peptidic toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s). They are similar to yeast and paramecium killing factors, and are structurally, functionally, and ecologically diverse. Applications of bacteriocins are being tested to assess their application as narrow-spectrum antibiotics.
Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram-negative infections including pneumonia. These may involve bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae, or Acinetobacter. It comes in two forms: colistimethate sodium can be injected into a vein, injected into a muscle, or inhaled, and colistin sulfate is mainly applied to the skin or taken by mouth. Colistimethate sodium is a prodrug; it is produced by the reaction of colistin with formaldehyde and sodium bisulfite, which leads to the addition of a sulfomethyl group to the primary amines of colistin. Colistimethate sodium is less toxic than colistin when administered parenterally. In aqueous solutions it undergoes hydrolysis to form a complex mixture of partially sulfomethylated derivatives, as well as colistin. Resistance to colistin began to appear as of 2015.
Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are classifications of antimicrobial agents based on their mode of action and specific to target organisms. The MDR types most threatening to public health are MDR bacteria that resist multiple antibiotics; other types include MDR viruses, parasites.
Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate and invertebrate animals, plants, and fungi. They are host defense peptides, with members displaying either direct antimicrobial activity, immune signaling activities, or both. They are variously active against bacteria, fungi and many enveloped and nonenveloped viruses. They are typically 18-45 amino acids in length, with three or four highly conserved disulphide bonds.
Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for antimicrobial peptides. These peptides are potent, broad spectrum antibiotics which demonstrate potential as novel therapeutic agents. Antimicrobial peptides have been demonstrated to kill Gram negative and Gram positive bacteria, enveloped viruses, fungi and even transformed or cancerous cells. Unlike the majority of conventional antibiotics it appears that antimicrobial peptides frequently destabilize biological membranes, can form transmembrane channels, and may also have the ability to enhance immunity by functioning as immunomodulators.
Pseudomonas aeruginosa is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, P. aeruginosa is a multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistance mechanisms, and its association with serious illnesses – hospital-acquired infections such as ventilator-associated pneumonia and various sepsis syndromes.
Tobramycin is an aminoglycoside antibiotic derived from Streptomyces tenebrarius that is used to treat various types of bacterial infections, particularly Gram-negative infections. It is especially effective against species of Pseudomonas.
Stenotrophomonas maltophilia is an aerobic, nonfermentative, Gram-negative bacterium. It is an uncommon bacterium and human infection is difficult to treat. Initially classified as Bacterium bookeri, then renamed Pseudomonas maltophilia, S. maltophilia was also grouped in the genus Xanthomonas before eventually becoming the type species of the genus Stenotrophomonas in 1993.
Fiona Brinkman is a Professor in Bioinformatics and Genomics in the Department of Molecular Biology and Biochemistry at Simon Fraser University in British Columbia, Canada, and is a leader in the area of microbial bioinformatics. She is interested in developing "more sustainable, holistic approaches for infectious disease control and conservation of microbiomes".
The resistome has been used to describe to two similar yet separate concepts:
Beta-defensin 2 (BD-2) also known as skin-antimicrobial peptide 1 (SAP1) is a peptide that in humans is encoded by the DEFB4 gene.
Polypeptide antibiotics are a chemically diverse class of anti-infective and antitumor antibiotics containing non-protein polypeptide chains. Examples of this class include actinomycin, bacitracin, colistin, and polymyxin B. Actinomycin-D has found use in cancer chemotherapy. Most other polypeptide antibiotics are too toxic for systemic administration, but can safely be administered topically to the skin as an antiseptic for shallow cuts and abrasions.
Hypothiocyanite is the anion [OSCN]− and the conjugate base of hypothiocyanous acid (HOSCN). It is an organic compound part of the thiocyanates as it contains the functional group SCN. It is formed when an oxygen is singly bonded to the thiocyanate group. Hypothiocyanous acid is a fairly weak acid; its acid dissociation constant (pKa) is 5.3.
Brilacidin, an investigational new drug (IND), is a polymer-based antibiotic currently in human clinical trials, and represents a new class of antibiotics called host defense protein mimetics, or HDP-mimetics, which are non-peptide synthetic small molecules modeled after host defense peptides (HDPs). HDPs, also called antimicrobial peptides, some of which are defensins, are part of the innate immune response and are common to most higher forms of life. As brilacidin is modeled after a defensin, it is also called a defensin mimetic.
The Catabolite repression control (Crc) protein participates in suppressing expression of several genes involved in utilization of carbon sources in Pseudomonas bacteria. Presence of organic acids triggers activation of Crc and in conjunction with the Hfq protein genes that metabolize a given carbon source are downregulated until another more favorable carbon source is depleted. Crc-mediated regulation impact processes such as biofilm formation, virulence and antibiotic susceptibility.
Murepavadin also known as POL7080 is a Pseudomonas specific peptidomimetic antibiotic. It is a synthetic cyclic beta hairpin peptidomimetic based on the cationic antimicrobial peptide protegrin I (PG-1) and the first example of an outer membrane protein-targeting antibiotic class with a novel, nonlytic mechanism of action, highly active and selective against the protein transporter LptD of Pseudomonas aeruginosa. In preclinical studies the compound was highly active on a broad panel of clinical isolates including multi-drug resistant Pseudomonas bacteria with outstanding in vivo efficacy in sepsis, lung, and thigh infection models. Intravenous murepavadin is in development for the treatment of bacterial hospital-acquired pneumonia and bacterial ventilator-associated pneumonia due to Pseudomonas aeruginosa.
Hans Gustaf Boman (1924-2008) was a Swedish microbiologist with a special focus on innate immunity. Boman was born on 16 August 1924 in Engelbrekt Parish, Stockholm, Sweden, and died on 3 December 2008. Boman's pioneering research on insect immunity formed the basis for the Nobel Prize in Physiology or Medicine 2011.
Multidrug-resistant bacteria are bacteria that are resistant to three or more classes of antimicrobial drugs. MDR bacteria have seen an increase in prevalence in recent years and pose serious risks to public health. MDR bacteria can be broken into 3 main categories: Gram-positive, Gram-negative, and other (acid-stain). These bacteria employ various adaptations to avoid or mitigate the damage done by antimicrobials. With increased access to modern medicine there has been a sharp increase in the amount of antibiotics consumed. Given the abundant use of antibiotics there has been a considerable increase in the evolution of antimicrobial resistance factors, now outpacing the development of new antibiotics.
Kalai Mathee is a professor at Florida International University, joint editor-in-chief of the Journal of Medical Microbiology, and an elected fellow of the American Academy of Microbiology. She is known for her research on bacterial infections caused by Pseudomonas aeruginosa.