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PhD candidate: Development of a multicellular 3-dimensional in vitro model of bone infection

Fracture related infection (FRI) is one of the most serious complications associated with the surgical fixation of bones fractured due to trauma. In our recent experimental studies in mice, we have characterized the pathology of ...

2 months

Arbeidsvoorwaarden

Standplaats:
Meibergdreef, Amsterdam, Noord-Holland
Dienstverband:
Tijdelijk contract / Tijdelijke opdracht
Uren per week:
36 - 36 uur
Opleidingsniveau:
WO

Functieomschrijving

Fracture related infection (FRI) is one of the most serious complications associated with the surgical fixation of bones fractured due to trauma. In our recent experimental studies in mice, we have characterized the pathology of Staphylococcus aureus FRI and shown that it involves the presence of bacterial biofilms on the surface of the implanted device, which is surrounded by accumulations of mostly necrotic neutrophils and fibrin. Finally, these structures are covered by an outer layer of fibrous encapsulation. We believe this clearly defined "FRI abscess" structure is central to the failure of the host defenses or antibiotic therapy to clear the infection, and ultimately for the failure of the fracture to heal.

The PhD candidate will be trained at the AMC in various courses relevant for his/her research, in compliance with the rules and regulations of the AMC Graduate School, and will graduate at the Faculty of Medicine of the University of Amsterdam. The project is performed within the research line of Dr. S.A.J. Zaat on “Biomaterial-associated infections and novel antimicrobial strategies” (http://www.amc.nl/SAJZaat) The research will mainly be carried out in the laboratories of the AO Research Institute in Davos, Switzerland, under the supervision of Dr. T.F. Moriarty, with regular visits to Amsterdam for training or specific research activities.

With this project, we aim to develop a 3-dimensional, multi-cellular in vitro cell culture model that replicates this "FRI abscess". This project will benefit from the availability of technical expertise within the project team in the use of 3-D cell culture models, which has been applied to tissue engineering and cancer immunology, but has not yet been extensively applied to infection biology. The key benefits of such a model will be the use of primary human cells, for which S. aureus has several specific targets not present in laboratory animals. This would also offer a more faithful recapitulation of the in vivo situation than may be achieved by conventional 2-dimensional co-culture systems. Once established, the 3-D model will be used to investigate the key bacterial and immune defense mechanisms responsible for abscess formation and resistance to therapy. Such advanced models will represent new tools for infection studies and for pre-clinical assessment of innovative treatments, and would be a significant advance for the field of implant related infection.

Functie-eisen

We are looking for a highly motivated PhD candidate for the project to be carried in laboratory in Davos.

Your position will include:

  • The development of novel multicellular in vitro models of staphylococcal bone infection (see project description below).

  • Summarize the current state of the art in the field of three-dimensional multicellular cell culture and its potential application in device related bone infection.

  • The successful candidate will be jointly supervised by the AO Research Institute Davos, and the AMC, Amsterdam, including to the extensive in-house facilities and expert collaborators at both institutions

Your profile:

  • Undergraduate degree in Microbiology, Cell Biology, Immunology, Biochemistry, or related field

  • Specific experience in the fields of bacterial infection or cell culture is preferred

  • Ability to work and communicate well within a team, complete project objectives and meet deadlines is essential

  • A working level of spoken and written English

  • Independent, structured and accurate way of working

  • Flexible and team orientated

Conditions

We offer an interesting, challenging and varied position in Davos with high value terms of employment. You will become part of a global network of dedicated professionals committed to innovation and excellence in patient care. Appointment takes place at the AO Foundation and will be for a period of 4 years. Gross monthly salary will be 3'500 Swiss Francs, and includes a 13th month end of year bonus payment. Holiday allowance is 25 days per year.

Being a PhD Graduate of AMC at the same time will offer access to the extensive research and training infrastructure of the AMC.

Project related travel between Switzerland and the Netherlands, and residence for approximately one month per year in the Netherlands will be required.

Additional information

If you feel you meet the requirements of this challenging opportunity please send your complete dossier (motivation letter, CV, certificates, references, etc.) to Dr. S.A.J. Zaat (s.a.zaat@amc.uva.nl) and Dr. Fintan Moriarty (fintan.moriarty@aofoundation.org)

Bedrijfsomschrijving

The project is a collaboration between the AMC and the AO Foundation.

The AO Foundation is a medically guided nonprofit organization led by an international group of surgeons specialized in the treatment of trauma and disorders of the musculoskeletal system. Founded in 1958 by 13 visionary surgeons, AO today fosters one of the most extensive networks of currently more than 12,000 surgeons, operating room personnel, and scientists in over 100 countries. For more information go to www.aofoundation.org.