The Fish Immunology and Vaccinology and the Biomolecular Structure groups of IBMC invite expressions of interest from candidates wishing to apply to a FCT-funded individual post-doctoral fellowship, for determining the three-dimensional structure of bacterial exotoxins (AIP56, NleC) and of the complexes formed with their targets. AIP56 is a novel bacterial exotoxin acting by triggering apoptosis in both macrophages and neutrophils, resulting in lysis of these phagocytes by post-apoptotic secondary necrosis [1,2]. Recently, we showed that AIP56 is a zinc-metalloprotease AB-type toxin that targets NF-kB [3]. Exerting their enzymatic activity on intracellular targets, AB toxins enter cells through a multi-step process involving specific binding to the cell surface, internalization via receptor-mediated endocytosis, and translocation into the cytosol [4]. Thus, elucidating the structure of this toxin will potentially enable the use of AIP56, or engineered AIP56 derivatives, as pharmacological and biological tools [5,6]. The candidates should hold a PhD in Biochemistry, Molecular Biology, or a related field. Although not mandatory, preference will be given to candidates with experience in protein expression and purification, macromolecular crystallization or X-ray crystallography. For additional information on FCT fellowships please visit http://www.fct.pt/apoios/bolsas/concursos/individuais2013.phtml.en. Any other enquiries should be addressed to Dr. N. Santos (nsantos_at_ibmc.up.pt).
References 1. do Vale A, Costa-Ramos C, Silva A, Silva DS, Gartner F, et al. (2007) Systemic macrophage and neutrophil destruction by secondary necrosis induced by a bacterial exotoxin in a Gram-negative septicaemia. Cell Microbiol 9: 988-1003. 2. do Vale A, Silva MT, dos Santos NMS, Nascimento DS, Reis-Rodrigues P, et al. (2005) AIP56, a novel plasmid-encoded virulence factor of Photobacterium damselae subsp. piscicida with apoptogenic activity against sea bass macrophages and neutrophils. Molecular Microbiology 58: 1025-1038. 3. Silva DS, Pereira LMG, Moreira AR, Ferreira-da-Silva F, Brito RM, et al. (2013) The Apoptogenic Toxin AIP56 Is a Metalloprotease A-B Toxin that Cleaves NF-κb P65. PLoS Pathog 9: e1003128. 4. Montecucco C, Papini E, Schiavo G (1994) Bacterial protein toxins penetrate cells via a four-step mechanism. FEBS Letters 346: 92-98. 5. Atassi MZ, Dolimbek BZ, Steward LE, Aoki KR (2007) Molecular bases of protective immune responses against botulinum neurotoxin A--how antitoxin antibodies block its action. Crit Rev Immunol 27: 319-341. 6. Holmgren J, Svennerholm A-M (2006) Engineered bacterial toxin vaccines and adjuvants. In: Alouf JE, Popoff MR, editors. The Comprehensive Sourcebook of Bacterial Protein Toxins: Academic Press. pp. 1008-1018. -- Pedro J. B. Pereira, PhD IBMC - Biomolecular Structure Group Rua do Campo Alegre, 823 4150-180 Porto Portugal Tel. +351 226 074 900 Fax +351 226 099 157
