Instituto de Tecnologia Química e Biológica
Application for a Research Fellowship
within project PTDC/BIA-PRO/118535/2010
Applications are invited for a Research Fellowship (BI) in the scope of the project entitled “Structural Biology of Histidine Kinases: a new target for novel antibacterial drugs”, ref. PTDC/BIA-PRO/118535/2010, through Fundação para a Ciência e a Tecnologia MEC/(PIDDAC)(FCT)
Scientific Area: Biological Sciences- Biology or related areas
Academic degree: Master degree (final grade above 16)
(i) Good capacity to perform both laboratorial and computational work with motivation to proceed to PhD; (ii) good knowledge of spoken and written english; (iii) ability to spend some periods abroad; (iv) preference will be given to candidates with previous experience in protein expression, purification, functional and structural characterization.
Enterococcus faecalis and Staphylococcus aureus are a leading cause of hospital-acquired infection. Both bacteria are now of major concern due to their increasing resistance to virtually all classes of antibiotics. In pathogenic bacteria, two-component signal transduction systems (TCSs) are pivotal in regulating virulence factor gene expression. They are also crucial for bacteria survival in their natural environment that fluctuates with respect to parameters such as pH, temperature, concentrations of nutrients and toxins. Generally, each TCS, consisting of a sensor histidine kinase (HK) and a response regulator (RR), respond to a specific environmental stress. Bacteria can possess numerous distinct TCS pairs to allow adaptational responses to a wide variety of environmental stimuli. The precise mechanisms by which signals are perceived by the kinases and transduced across the membrane remain elusive, particularly in the absence of inta ct protein structures possessing their transmembrane and sensory domains.
The aim of this project is to determine the three-dimensional structure of intact sensor HKs from Enterococcus and Staphylococcus. These HK proteins are of clinical importance, and have been proposed as excellent targets for the design of novel antibacterial drugs. Moreover, studying these sensor HKs is fundamental to further understand the mechanism by which bacteria interact with the environment.
Tasks to be performed within this project involve cloning, expression and purification of several histidine kinases; biochemical/biophysical studies and structural characterization by X-ray crystallography, which includes both laboratorial and computational work. The project will be developed in collaboration with Membrane Protein Laboratory, Diamond Light Source, Oxfordshire, UK (I. Moraes) and University of Central Lancashire, UK (M. Phillips-Jones).
Applicable Law and Regulations: Law 40/2004 of 18 August (“Estatuto do Bolseiro de Investigação Científica”), changed and republished by Ordinance 202/2013 of 27 Algust and changed by Ordinance 233/2012 of 29 October and by Law 12/2013 of 29 January and by Ordinance 89/2013 of 9 July; Fellowship Regulations of Fundação para a Ciência e Tecnologia, I.P. – 2013; Fellowship Regulations of Instituto de Tecnologia Química e Biológica (ITQB).
Working Place: The work will be done in the Laboratory of Membrane Protein Crystallography at ITQB under supervision of Dr Margarida Archer Frazão.
Duration of the fellowship: The fellowship will have the duration of 3 months (eventually renewable), expected to start in July 2014, on a full-time basis, according to Fellowship Regulations of Fundação para a Ciência e Tecnologia, I.P. – 2013; Fellowship Regulations of Instituto de Tecnologia Química e Biológica (ITQB).
Stipend amount: € 980, according to the values of FCT Scientific Fellowships in Portugal (http://alfa.fct.mctes.pt/apoios/bolsas/valores).
Selection procedure: The selection procedures will be based on the curricular evaluation (50%) and previous experience in the requested areas (50%). An interview with the selected candidates may take place.
Juri composition: Margarida Archer Frazão (President), José Brito and Tânia Oliveira; Célia Romão and Tiago Bandeiras (as substitutes).
Application documents: The application should be formalised in a cover letter indicating the corresponding fellowship reference together with the following documents: detailed Curriculum Vitae, degree certificate (with disciplines and grades), motivation letter and 2 references.
Notification of candidates: All the candidates will be informed by e-mail of the final result.
Application period: from May 26 to June 6 2014.
Applications should be sent to:
Doutora Margarida Archer Frazão
Membrane Protein Crystallography Laboratory
archer en itqb.unl.pt