Prof. Ralph Müller

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.

Project 1 – Establishing a 3D In Vitro Co-culture of Osteoclasts and Osteoblasts Bone cells such as osteoclasts, and osteoblasts have significant roles in bone remodeling. So far in our models, we have established long-term culture of osteoblasts and osteocytes. However, bone-resorbing cells such as osteoclasts were not incorporated into the system. In this project, human osteoclast precursors will be introduced, and functional and molecular biology assays will be established along with the time-lapsed microCT scans. Furthermore, the interplay of cell-mediated resorption and formation of extracellular matrix will be evaluated with time-lapsed CT scans and molecular biology assays. This project can be tailored to suit a Bachelor’s Thesis, semester Project or research internship. The students will receive hands-on experience in handling primary cells, bioreactors, 3D printing and conducting molecular biology assays. Project 2 – Optimization of Fibrin as A Bioink for 3D Bioprinting Fibrin-based bioink formulations have garnered research interest due to their excellent biological properties. It is widely used in clinics as a hemostatic agent and surgical sealant. Fibrin and fibrinogen-based proteins are known to have diverse roles in different stages of tissue repair such as cell adhesion, inflammation, angiogenesis, and remodeling. The goal of this project is to develop a 3D printable bio-ink formulation of fibrin and mechanical properties will be tailored to support human mesenchymal stem cell differentiation. This project can be tailored to suit a Masters’ Thesis, Semester Project or Research Internship. The students will receive hands-on experience in primary cell cultivation, inkjet printing, extrusion 3D printing and molecular biology assays.

The projects are multidisciplinary, and students from biology, bioengineering and mechanical engineering backgrounds are welcome. The project goals could be tailored to the student’s interests, expertise, and project requirements.

Dr Chris Steffi (e-mail: chris.steffi@hest.ethz.ch), Postdoc, Laboratory for Bone Biomechanics, ETH Zurich. If you wish to apply, please upload your CV, motivation letter, and academic transcripts on SiROP or email them to me directly. Incomplete submissions will not be considered.

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.