[OFER-TRABEC] NAC: Host-Pathogen Interactions

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---Procedencia:
Institución:Instituto de Biologia Molecular e Celular - IBMC, Porto
Contacto correo-e:nsantos@ibmc.up.pt
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AIP56 was identified at our laboratory as a novel bacterial exotoxin acting by triggering apoptosis in both macrophages and neutrophils, resulting in lysis of these phagocytes by post-apoptotic secondary necrosis. Recently we have shown that AIP56 is a zinc-metalloprotease AB-type toxin that targets NF-kB. Displaying 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. The structure of those toxins is adapted to their entry mechanisms and, to this end, these toxins are organized in a so-called AB-type structure consisting of a catalytic A subunit disulfide-bound to a cell interacting B subunit(s) that mediate toxin binding to a cell receptor and delivery of the catalytic A subunit into the cytosol.
NF-kB is a transcription factor playing a major role in immunobiology by regulating the expression of hundreds of genes involved in cell death, proliferation and differentiation, as well as innate and adaptive immune responses, and its uncontrolled activation or inactivation is associated with several severe human pathologies, such as inflammatory diseases and cancer.
Thus, gaining insights into the structure of AIP56 will potentially enable the use of AIP56, or engineered AIP56 derivatives as pharmacological and biological tools, as well as designing therapeutic and prophylactic (e.g. vaccines) measures. Toxins are remarkably specific, extremely potent and extraordinarily efficient, which prompts researchers to use them for research, biotechnology or medical treatments. Examples of toxins most often used as tools include pore-forming toxins (e.g. tetanolysin), neurotoxins targeting synaptic proteins (e.g. Clostridium botulinum neurotoxins) and toxin-based cell delivery systems (e.g. diphtheria and anthrax toxins). Finally, Disclosing the AIP56 structure will provide a unique opportunity to study its structure-function relationship.
In the above context, the main goal of this working proposal is to carry out a detailed characterization of AIP56 in order to identify minimum functional-structural domains required for receptor binding, membrane translocation and enzymatic activity, as well as determining the three-dimensional structure of the toxin by X-ray crystallography.

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Información complementaria de la oferta:
IBMC, a leading and dynamic research institution in the field of Life and Health Sciences is opening 1 (one) Postdoctoral Fellowships to join its Research Program in Host-Pathogen Interactions. We are looking for a Fellow holding a PhD in Biochemistry, Molecular Biology, Biology, Microbiology or a related field. Preference will be given to candidates with previous postdoctoral experience, as well as experience in protein expression and purification, macromolecular crystallization or X-ray crystallography. English language, both spoken and written, and good inter-personal relationships in the context of a multidisciplinary research team are essential attributes.

Initially for 1 year, the Postdoctoral Fellowship is renewable maximum until June 30th 2015.

The selected candidate will benefit from an excellent research environment, and have access to state of the art facilities including Advanced Light Microscopy, Flow Cytometry, Genotyping, Animal House (including antibody production), P3 Facilities, Electron Microscopy, Protein Production and Purification (http://www.ibmc.up.pt/research/research-facilities).

The fellowship amount is 1495 euros per month (tax free), paid by bank transfer, preferentially
(http://alfa.fct.mctes.pt/apoios/bolsas/valores)

Applications should be received until April 6th, 2013. The Postdoctoral Fellowship is expected to start in April
15th 2014.
Selection Comitte:
Nuno dos Santos, PhD
Ana do Vale, PhD
Pedro Pereira, PhD
To apply for the Postdoctoral Fellowships interested candidates must hold a PhD degree and submit the
following documents a) Complete CV; b) Letter of Motivation; and 2 referee's letters via the online application
system: http://www.ibmc.up.pt/gestaocandidaturas/index.php?codigo=ON2201306

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