Gabriel WaksmanFMedSci, FRS, is Courtauld professor of biochemistry and molecular biology at University College London (UCL), and professor of structural and molecular biology at Birkbeck College, University of London. He is the director of the Institute of Structural and Molecular Biology (ISMB) at UCL and Birkbeck, head of the Department of Structural and Molecular Biology at UCL, and head of the Department of Biological Sciences at Birkbeck.
Waksman's laboratory studies the structures and mechanisms of large nanomachines involved in bacterial secretion with particular emphasis on pilus biogenesis by the Chaperone-Usher pathway and on Type IV Secretion (T4S) Systems. The Waksman laboratory primarily uses X-ray Crystallography and Electron Microscopy to determine 3D structures as well as biochemical and biophysical techniques to uncover the mechanisms used by these nanomachines.[citation needed]
T4S systemsedit
These systems are present in both Gram-negative and Gram-positive bacteria. They form multi-megadalton machines embedded in membranes and are responsible for the secretion of both proteins and nucleic acid substrates. They play major roles in pathogenicity of, for example, Helicobacter pylori, the causative agent of ulcers. They also mediate transfer of plasmid DNAs during conjugation, a process that leads to the spread of antibiotics resistance genes. T4S systems are composed of 12 proteins named VirB1-11 and VirD4 that assemble into a formidable nanomachine of more than 3 megadalton in size and spanning the 2 membranes of Gram-negative bacteria.[1][2][3][4]
Pilus biogenesisedit
Bacterial pili are hair-like surface-exposed organelles. They are responsible for recognition of and attachment to the host and thus, are also crucial virulence factors. Pili are polymer of protein subunits, the assembly of which requires accessory proteins. The Waksman lab engages in research on pili assembled by the Chaperone-Usher (CU) pathway. (CU) pili have clear relevance in the pathogenicity of uropathogenic Escherichia coli, where CU pili mediate bacterial tropism to the bladder to cause cystitis or to the kidney to cause pyolenephritis. CU pili require two accessory proteins for biogenesis: a chaperone that stabilises pilus subunits and ferries them to an assembly platform, the usher, the second accessory protein required in this system. The usher is an extraordinary molecular nanomachine embedded in the outer membrane. It drives subunit recruitment, polymerisation and secretion.[5][6][7][8][9][10]
Education and careeredit
Waksman obtained his PhD in Fundamental Biochemistry at the University of Paris in 1982 and after military service in Ivory Coast, worked for Rhone Poulenc Agrochimie as staff scientist. In 1987, he left the company to work as a postdoctoral assistant at Bristol University and the University of Sheffield, and in 1991, moved to the USA to work as a postdoctoral associate in the laboratory of Professor John Kuriyan.
In 1993, Waksman set up his independent laboratory at Washington University School of Medicine in the Department of Biochemistry and Molecular Biophysics where, in 2000, he was appointed the first Roy and Diana Vagelos endowed Professor of Biochemistry and Molecular Biophysics. In 2002, he moved to London to set up the Institute of Structural and Molecular Biology.
^Low HH, Gubellini F, Rivera-Calzada A, et al. (April 2014). "Structure of a type IV secretion system". Nature. 508 (7497): 550–3. Bibcode:2014Natur.508..550L. doi:10.1038/nature13081. PMC3998870. PMID 24670658.
^Trokter M, Felisberto-Rodrigues C, Christie PJ, Waksman G (April 2014). "Recent advances in the structural and molecular biology of type IV secretion systems". Current Opinion in Structural Biology. 27C: 16–23. doi:10.1016/j.sbi.2014.02.006. PMC4182333. PMID 24709394.
^Chandran V, Fronzes R, Duquerroy S, Cronin N, Navaza J, Waksman G (December 2009). "Structure of the outer membrane complex of a type IV secretion system". Nature. 462 (7276): 1011–5. Bibcode:2009Natur.462.1011C. doi:10.1038/nature08588. PMC2797999. PMID 19946264.
^Fronzes R, Schäfer E, Wang L, Saibil HR, Orlova EV, Waksman G (January 2009). "Structure of a type IV secretion system core complex". Science. 323 (5911): 266–8. doi:10.1126/science.1166101. PMC6710095. PMID 19131631.
^Allen WJ, Phan G, Waksman G (August 2012). "Pilus biogenesis at the outer membrane of Gram-negative bacterial pathogens". Current Opinion in Structural Biology. 22 (4): 500–6. doi:10.1016/j.sbi.2012.02.001. PMID 22402496.
^Busch A, Waksman G (April 2012). "Chaperone-usher pathways: diversity and pilus assembly mechanism". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 367 (1592): 1112–22. doi:10.1098/rstb.2011.0206. PMC3297437. PMID 22411982.
^Geibel S, Procko E, Hultgren SJ, Baker D, Waksman G (April 2013). "Structural and energetic basis of folded-protein transport by the FimD usher". Nature. 496 (7444): 243–6. Bibcode:2013Natur.496..243G. doi:10.1038/nature12007. PMC3673227. PMID 23579681.
^Phan G, Remaut H, Wang T, et al. (June 2011). "Crystal structure of the FimD usher bound to its cognate FimC-FimH substrate". Nature. 474 (7349): 49–53. doi:10.1038/nature10109. PMC3162478. PMID 21637253.
^Dodson KW, Pinkner JS, Rose T, Magnusson G, Hultgren SJ, Waksman G (June 2001). "Structural basis of the interaction of the pyelonephritic E. coli adhesin to its human kidney receptor". Cell. 105 (6): 733–43. doi:10.1016/S0092-8674(01)00388-9. PMID 11440716. S2CID 7008277.
^Sauer FG, Fütterer K, Pinkner JS, Dodson KW, Hultgren SJ, Waksman G (August 1999). "Structural basis of chaperone function and pilus biogenesis". Science. 285 (5430): 1058–61. doi:10.1126/science.285.5430.1058. PMID 10446050.
^"The Academy of Medical Sciences: Fellows directory". The Academy of Medical Sciences.
^"The Royal Society Biography". The Royal Society.
External linksedit
Official home page at the University of London
April 13, 2024
gabriel, waksman, this, biography, living, person, relies, much, references, primary, sources, please, help, adding, secondary, tertiary, sources, contentious, material, about, living, persons, that, unsourced, poorly, sourced, must, removed, immediately, espe. This biography of a living person relies too much on references to primary sources Please help by adding secondary or tertiary sources Contentious material about living persons that is unsourced or poorly sourced must be removed immediately especially if potentially libelous or harmful Find sources Gabriel Waksman news newspapers books scholar JSTOR September 2014 Learn how and when to remove this template message Gabriel Waksman FMedSci FRS is Courtauld professor of biochemistry and molecular biology at University College London UCL and professor of structural and molecular biology at Birkbeck College University of London He is the director of the Institute of Structural and Molecular Biology ISMB at UCL and Birkbeck head of the Department of Structural and Molecular Biology at UCL and head of the Department of Biological Sciences at Birkbeck Contents 1 Research 2 T4S systems 3 Pilus biogenesis 4 Education and career 5 Recognition 6 References 7 External linksResearch editWaksman s laboratory studies the structures and mechanisms of large nanomachines involved in bacterial secretion with particular emphasis on pilus biogenesis by the Chaperone Usher pathway and on Type IV Secretion T4S Systems The Waksman laboratory primarily uses X ray Crystallography and Electron Microscopy to determine 3D structures as well as biochemical and biophysical techniques to uncover the mechanisms used by these nanomachines citation needed T4S systems editThese systems are present in both Gram negative and Gram positive bacteria They form multi megadalton machines embedded in membranes and are responsible for the secretion of both proteins and nucleic acid substrates They play major roles in pathogenicity of for example Helicobacter pylori the causative agent of ulcers They also mediate transfer of plasmid DNAs during conjugation a process that leads to the spread of antibiotics resistance genes T4S systems are composed of 12 proteins named VirB1 11 and VirD4 that assemble into a formidable nanomachine of more than 3 megadalton in size and spanning the 2 membranes of Gram negative bacteria 1 2 3 4 Pilus biogenesis editBacterial pili are hair like surface exposed organelles They are responsible for recognition of and attachment to the host and thus are also crucial virulence factors Pili are polymer of protein subunits the assembly of which requires accessory proteins The Waksman lab engages in research on pili assembled by the Chaperone Usher CU pathway CU pili have clear relevance in the pathogenicity of uropathogenic Escherichia coli where CU pili mediate bacterial tropism to the bladder to cause cystitis or to the kidney to cause pyolenephritis CU pili require two accessory proteins for biogenesis a chaperone that stabilises pilus subunits and ferries them to an assembly platform the usher the second accessory protein required in this system The usher is an extraordinary molecular nanomachine embedded in the outer membrane It drives subunit recruitment polymerisation and secretion 5 6 7 8 9 10 Education and career editWaksman obtained his PhD in Fundamental Biochemistry at the University of Paris in 1982 and after military service in Ivory Coast worked for Rhone Poulenc Agrochimie as staff scientist In 1987 he left the company to work as a postdoctoral assistant at Bristol University and the University of Sheffield and in 1991 moved to the USA to work as a postdoctoral associate in the laboratory of Professor John Kuriyan In 1993 Waksman set up his independent laboratory at Washington University School of Medicine in the Department of Biochemistry and Molecular Biophysics where in 2000 he was appointed the first Roy and Diana Vagelos endowed Professor of Biochemistry and Molecular Biophysics In 2002 he moved to London to set up the Institute of Structural and Molecular Biology Recognition editElected member of European Molecular Biology Organization EMBO in 2007 Elected fellow of the Academy of Medical Sciences in 2008 11 Elected fellow of the Royal Society in 2012 12 Elected a member of the German Academy of Sciences Leopoldina in 2013References edit Low HH Gubellini F Rivera Calzada A et al April 2014 Structure of a type IV secretion system Nature 508 7497 550 3 Bibcode 2014Natur 508 550L doi 10 1038 nature13081 PMC 3998870 PMID 24670658 Trokter M Felisberto Rodrigues C Christie PJ Waksman G April 2014 Recent advances in the structural and molecular biology of type IV secretion systems Current Opinion in Structural Biology 27C 16 23 doi 10 1016 j sbi 2014 02 006 PMC 4182333 PMID 24709394 Chandran V Fronzes R Duquerroy S Cronin N Navaza J Waksman G December 2009 Structure of the outer membrane complex of a type IV secretion system Nature 462 7276 1011 5 Bibcode 2009Natur 462 1011C doi 10 1038 nature08588 PMC 2797999 PMID 19946264 Fronzes R Schafer E Wang L Saibil HR Orlova EV Waksman G January 2009 Structure of a type IV secretion system core complex Science 323 5911 266 8 doi 10 1126 science 1166101 PMC 6710095 PMID 19131631 Allen WJ Phan G Waksman G August 2012 Pilus biogenesis at the outer membrane of Gram negative bacterial pathogens Current Opinion in Structural Biology 22 4 500 6 doi 10 1016 j sbi 2012 02 001 PMID 22402496 Busch A Waksman G April 2012 Chaperone usher pathways diversity and pilus assembly mechanism Philosophical Transactions of the Royal Society of London Series B Biological Sciences 367 1592 1112 22 doi 10 1098 rstb 2011 0206 PMC 3297437 PMID 22411982 Geibel S Procko E Hultgren SJ Baker D Waksman G April 2013 Structural and energetic basis of folded protein transport by the FimD usher Nature 496 7444 243 6 Bibcode 2013Natur 496 243G doi 10 1038 nature12007 PMC 3673227 PMID 23579681 Phan G Remaut H Wang T et al June 2011 Crystal structure of the FimD usher bound to its cognate FimC FimH substrate Nature 474 7349 49 53 doi 10 1038 nature10109 PMC 3162478 PMID 21637253 Dodson KW Pinkner JS Rose T Magnusson G Hultgren SJ Waksman G June 2001 Structural basis of the interaction of the pyelonephritic E coli adhesin to its human kidney receptor Cell 105 6 733 43 doi 10 1016 S0092 8674 01 00388 9 PMID 11440716 S2CID 7008277 Sauer FG Futterer K Pinkner JS Dodson KW Hultgren SJ Waksman G August 1999 Structural basis of chaperone function and pilus biogenesis Science 285 5430 1058 61 doi 10 1126 science 285 5430 1058 PMID 10446050 The Academy of Medical Sciences Fellows directory The Academy of Medical Sciences The Royal Society Biography The Royal Society External links editOfficial home page at the University of London Retrieved from https en wikipedia org w index php title Gabriel Waksman amp oldid 1205547165, wikipedia, wiki, book, books, library,
