SNSF-funded PhD Position in Advanced In Vivo Imaging of Heterotopic Ossification in Zürich

The Laboratory for Bone Biomechanics (LBB) at the Institute for Biomechanics at ETH Zurich is offering a PhD position in advanced in vivo imaging of heterotopic ossification. This position is embedded within the (Nr. 213520; project start 01.04.2023; collaboration partners: M. Bohner, RMS Foundation, Bettlach; R. Müller, ETH Zurich; E. Wehrle, ARI Davos) focusing on a newly-proposed mechanism explaining the formation of bone in soft tissue, also called heterotopic ossification (). According to this mechanism, tissue mineralization may provoke a sustained local ionic homeostatic imbalance (SLIHI), and this local decrease in extracellular calcium may modulate inflammation to trigger bone formation. The general project aim is to assess the validity of this mechanism and to use it for healing large bone defects.

Heterotopic ossification (HO) is a very common and sometimes highly debilitating pathology characterized by the formation of mature bone in soft tissues. The underlying mechanisms are still poorly-understood and therapies to prevent and heal HO have a low efficiency. It is not uncommon that bone has to be removed surgically. This formation of bone in soft tissue is the result of an osteoinductive process during which stem cells are differentiated into bone cells. This property is essential to treat large bone defects. Currently, osteoinduction can be achieved by the implantation of bone morphogenetic proteins (BMPs), but the safety of BMP has been questioned. Another approach is to implant osteoinductive bone graft substitutes, but their potency is low, and the underlying mechanisms are still debated. Demonstrating that a low extracellular calcium concentration is key in triggering bone formation and having a better understanding of this process could open up new opportunities in the design of potent osteoinductive bone graft substitutes and the treatment of impaired bone healing.

Project team and setup: Within the project, we will follow a multidisciplinary collaborative approach for which we are recruiting 3 PhD students focusing on material science (), advanced in vivo imaging and computation () and in vivo molecular biology (). An additional Postdoc position () will be focusing on the development of multiphoton intravital imaging technology. This multidisciplinary team setup will allow to design calcium phosphate materials with controlled architecture, composition, and to assess their rate of mineralization in vitro and in vivo. The level of extracellular calcium and the tissue response around the materials will be followed by multimodal approaches including (among others) time-lapsed in vivo imaging, multiphoton intravital microscopy, spatial transcriptomics and proteomics.

For the advanced in vivo imaging work packages within SLIHI4BONE, we are looking for a motivated PhD candidate to join the Laboratory for Bone Biomechanics at ETH Zurich. You will closely interact with the Sinergia collaboration partners at RMS Foundation and ARI Davos. You will be enrolled in the PhD program of ETH Zurich. Tasks and activities will include:

• Development of advanced in vivo imaging protocols for HO and impaired bone healing using time-lapsed micro-computed tomography and multiphoton imaging
• Extension of internal Python-based computational framework for 4D image analysis and morphometric quantification
• Imaging and computational support for in vivo experiments

• MSc degree in engineering science or related discipline
• Previous programming experience in Python is required
• Previous experience with imaging and/or image analysis is advantageous
• Experience with computed tomography and/or multiphoton microscopy is advantageous
• Excellent communication skills in English (oral and written) are a must
• High motivation, strong interest in skeletal research, durability to cope with challenges
• Ability to solve complex tasks in a highly independent manner
• Familiarity with a cross-cultural/interdisciplinary environment is an advantage

• An interesting and varied job in exciting and innovative organizations
• Working in a highly committed multidisciplinary team
• Regular meetings and close collaboration with the Sinergia project partners
• Enrolment in the PhD program of ETH Zurich
• ETH Zurich is a family-friendly employer with excellent working conditions with an exciting working environment, cultural diversity and attractive offers and benefits