Prof. Ralph Müller

Students will engage in a project examining **protein expression within fracture sites** of **young** **vs**. **aged** and **male** **vs**. **female** mice subjected to either **controlled** **mechanical** **loading** or **sham** **loading**. By combining spatial proteomic profiling with mechanical analyses (that is, finite element modelling), students will explore how the **local** **mechanical** **environment** **of** **individual** **cells** governs their proteomic responses—and how this mechano-sensitivity changes with age and sex. This is a highly interdisciplinary project suited to students interested in musculoskeletal biology, spatial omics, image analysis, mechanical engineering, computational modelling, or mechanobiology. Student project opportunities will focus on a combination of experimental techniques, computational analyses, and the development of integrated pipelines.

We are interested in the following: • Develop a **protein**-**level** understanding of mechanobiological regulation during bone healing. • Identify how **aging** **and** **sex** alter mechano-sensitive protein expression patterns. • Relate **local** **mechanical** **cues** to **cellular** **proteomic** **responses** during fracture repair.

Please contact Neashan Mathavan via: nmathavan@ethz.ch Obs! Please include your CV and academic transcript (i.e. list of courses you have completed with grades) with any expression of interest in this project.

Bone defects that do not heal spontaneously despite surgical stabilization and require further surgical intervention are termed critical sized defects (CSD). They pose dramatic consequences to a person’s well-being and life expectancy due to their impact on the skeletal system’s integrity. Bone graft substitutes (BGS) present a treatment approach by enhancing and facilitating the natural healing capacity of the bone tissue using their osteoconductive and osteoinductive potential and filling up the physical space of lost bone for mechanical support. The key property of a BGS in treatment of a large bone defect is osteoinduction. Physiological processes in bone usually happen on different spatial scales, spanning from the whole organ, to tissue, to cellular and even to the molecular level. Therefore, an ideal imaging setup to **unravel the underlying mechanisms of material-induced osteoinduction** would require a **multiscale approach** to connect orang and tissue level processes with the cellular and subcellular scale. Micro-CT can be considered the gold standard in hierarchical 3D imaging of bone structure and function and allows a non-destructive _ex vivo_ and _in vivo_ image acquisition. **Time-lapsed _in vivo_ micro-CT images** can reveal distinct information on the longitudinal development of implant calcification or resorption. However, its resolution is relatively low and certain details can not be detected. _Ex vivo_ micro-CT on the other hand allows scans of higher resolution and therefore complements the _in vivo_ micro-CT well. The 3D-3D registration of high-resolution _ex vivo_ and low-resolution _in vivo_ micro-CT images generates a multiscale micro-CT imaging approach. Advanced image analysis methods can help identify newly formed bone and generally distinguish bone and the BGS. By combined analysis of multiscale micro-CT measurements of murine femur samples with implanted ectopic or orthotopic BGS, critical 3D mineralization behavior in material-induced osteoinduction can be investigated.

Developing a framework (Python) for the successful (semi-automated) registration of _in vivo_ and _ex vivo_ micro-CT images and advanced image analysis methods of the same murine femur micro-CT scans with BGS for the assessment of 3D mineralization behavior in material-induced osteoinduction. Previous knowledge of python programming and advanced image analysis are of advantage. However, the project goals will be tailored to the student’s interests, expertise, and current project requirements.

Sara Lindenmann, doctoral student (e-mail: sara.lindenmann@hest.ethz.ch), ETH Zürich / Laboratory for Bone Biomechanics (https://www.bone.ethz.ch/) For application, please provide your CV and transcripts of B.Sc. and M.Sc.

To address this century-old problem, the Laboratory for Bone Biomechanics has established a novel approach termed “spatial mechanomics”. Spatial mechanomics is defined as the integration of spatially-resolved “omics” with in silico models of the mechanical environment to investigate the interactions between local mechanical environments and cellular / molecular responses (Figure 1). This is a highly cross-disciplinary area of research combining in vivo models, imaging, “omics” techniques, mechanical testing and computational modelling / analyses. There are opportunities for student projects within this area of research that can be tailored to suitable candidates. Ideally applicants will be candidates with an interest or experience in musculoskeletal research, “omics” techniques, computational analyses, mechanical engineering, histology and/or image processing.

We are interested in the following: • To develop a molecular-based understanding of bone healing mechanobiology. • To investigate how this mechano-sensitivity is compromised with age.

Please contact Neashan Mathavan via: nmathavan@ethz.ch Obs! Please include your CV and academic transcript (i.e. list of courses you have completed with grades) with any expression of interest in this project.