Gabriel Waksman
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.
Research
Gabriel 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.
T4S systems
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 biogenesis
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 career
Gabriel 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.
Recognition
- Elected Member of European Molecular Biology Organization (EMBO) in 2007
- Elected Fellow of the Academy of Medical Sciences in 2008
- Elected Fellow of the Royal Society in 2012
- Elected a Member of the German Academy of Sciences Leopoldina in 2013
References
- ↑ Low HH, Gubellini F, Rivera-Calzada A, et al. (April 2014). "Structure of a type IV secretion system". Nature 508 (7497): 550–3. doi:10.1038/nature13081. 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. 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. doi:10.1038/nature08588. PMC 2797999. 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. 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. 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.
- ↑ 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.