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Bone Biology & Orthopaedic Research of the Department Clinical Research of the Medical Faculty
University of Bern, Switzerland
Closing date: Thu 31 Aug 2017
Bone Morphogenetic Proteins (BMP) are members of the TGFβ-superfamily of growth factors and have originally been characterized as ostegenic mediators. Although BMP have completed an accomplished career since their original description in 1988, and are used in dental and orthopaedic practice for the augmentation of bone, the mechanisms of action are far from being elucidated. A major question concerns the need for supraphysiological amounts of BMP in clinical settings, which is accompanied by osteolysis. It was suggested that BMP-antagonists are induced as part of the reaction of mesenchymal lineage cells to BMP2. Additional experiments led to the hypothesis that Noggin action is not restricted to an anti-osteogenic effect by blocking BMP actions, but that Noggin supports osteoclastogenesis through a direct and eventually receptor-mediated mechanism.
The elucidation of the mechanisms of the osteolastogenic effects of Noggin will be the aim of the present proposal. Evidence has been collected that Noggin, by an as yet unknown pathway, activates TGFβ signaling. Furthermore, RANKL signaling was linked to the family of lgr orphan receptors which may be activated by R-spondins and by Noggin.
Within this project, we will use in vitro models for the generation of osteoclasts to investigate the roles of the above mentioned signaling pathways in osteoclast development and activation. Furthermore, lineage specific knock-out mice will be generated to assess the physiological roles of specific proteins of interest.
The data from this study will provide new information on the action of BMPs in bone healing. This in turn will enable clinicians to improve the therapeutic protocols of BMP applications, minimizing both the risk to the patient and potential side effects.
For this project we seek a highly motivated student with interest in a pre-clinical project with strong interactions with clinicians. An education in Biology, Medical Sciences and familiarity with Molecular Biology and/ or Cell Biology and/ or Physiology is recommendable. Competence in communicating in English, both spoken and written, are a prerequisite, as is the willigness to collaborate in an interdisciplinary environment.
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6-7 March 2018, Conference Aston, Birmingham
News, 10 August
26-28 March 2018, Merton College, Oxford, UK