Müller Group / Laboratory for Bone BiomechanicsOpen OpportunitiesCombine two exploding fields in computer science: machine learning and agent-based modelling.
Based on preclinical and in vitro studies of cell behaviour and cytokine reaction-diffusion and mechanical tests we have generated an in-house biofidelic agent-based model of the human skeleton and its response to diseases and their treatments. This model reproduces the effects of several widely used osteoporosis treatments on key parameters used to quantify fracture risk. This rule-based approach involves studying bone mechanobiology at the cell scale and extrapolating this to millions of cells at the tissue scale to understand the pharmacokinetics of treatments and identify possible new therapies and approaches to patient-specific treatment.
An alternative approach to in silico prediction of response to treatment is a supervised learning approach where we simply input baseline and follow-up bone scans to a CNN with twelve layers constructed using keras. We then attempt to dive into the black box and quantify what characteristics of the input govern the response of our model. The issue is the clinical data is not big enough to do this well so we use the agent-based model as input to the ML approach to construct a proxy model! This also helps us understand, validate and quantify the uncertainty in the agent-based model. To decide which runs of the agent-based model to use as input to the ML approach to construct the proxy model we use polynomial chaos expansion. - Animal Physiology-Cell, Artificial Intelligence and Signal and Image Processing, Cell Development (incl. Cell Division and Apoptosis), Cellular Interactions (incl. Adhesion, Matrix, Cell Wall), Computation Theory and Mathematics, Modeling and Simulation, Protein Targeting and Signal Transduction
- Bachelor Thesis, Master Thesis, Semester Project
| Delayed bone healing or failed non-unions account for 5 – 10% of all bone fractures and present a challenging problem in regenerative medicine. The impact of delayed unions or non-unions can be devastating with prolonged rehabilitation, decreased quality of life and significant health care costs. Our lab has conducted fracture healing studies in young and prematurely-aged mouse models with different defect sizes. The aim of this project is to analyse data from mice which exhibit delayed unions and non-unions. - Biomaterials, Biomechanical Engineering
- Bachelor Thesis, Internship, Master Thesis, Semester Project
| Bone exhibits a remarkable ability to adapt its microstructure in response to mechanical and metabolic demands. This process involves a dynamic balance between bone-forming osteoblasts and bone-resorbing osteoclasts, with osteocytes playing a crucial role in signaling micro-mechanical cues. Disruptions in these mechanisms, as seen in conditions like postmenopausal osteoporosis, lead to decreased bone density and increased fracture risk. Sclerostin is pivotal in determining bone formation or resorption in response to mechanical stimuli and is targeted by FDA-approved osteoporosis medications. However, the drug's mechanism and its interaction with mechanical loading remain unclear. This project aims to investigate bone's response to sclerostin antibody treatment and uncover the cellular mechanisms governing bone adaptation using single-cell mechanomics cluster analysis. - Computational Biology and Bioinformatics, Engineering and Technology, Mathematical Sciences, Medical and Health Sciences, Physics
- Bachelor Thesis, Internship, Master Thesis, Semester Project
| Fracture healing is a complex process that involves inflammation, angiogenesis, and bone remodeling. The remodelling process helps maintain bone density, repair micro-damage that occurs due to everyday activities, and adapt bones to the specific needs of an individual's body. Mechanical loading is a crucial factor in the regulation of fracture healing. The forces and strains experienced by the bone during everyday activities influence the cellular responses, callus formation, bone deposition, remodelling, and, ultimately, the successful recovery of the fractured bone. The mechanisms underlying spatial cell reorganization during loading, which contributes to fracture healing, remain unclear. The project aims to investigate and explore the fracture healing process of mice using spatial transcriptome changes in response to mechanical loading. By shedding light on this aspect, the project aims to contribute to the broader understanding of fracture healing and potentially pave the way for more effective treatment strategies in the future. - Biological Mathematics, Computational Biology and Bioinformatics, Engineering and Technology, Information, Computing and Communication Sciences, Medical and Health Sciences, Physics
- Bachelor Thesis, Course Project, ETH for Development (ETH4D) (ETHZ), ETH Zurich (ETHZ), IDEA League Student Grant (IDL), Internship, Master Thesis, Semester Project
| Bone is a metabolically active, rigid connective tissue that provides structural support, facilitates movement, and protects vital organs. Micro-computed tomography (micro-CT) is a widely employed imaging technology to gain deeper insights into bone structure and function. We have recently introduced the mi-CT image data repository, an open-access platform dedicated to biomedical images obtained from micro-CT scans within our research group (https://www.mi-ct.ethz.ch/). This repository aims to facilitate research by developing an efficient online image management system, making the data easily accessible. Achieving open access to these tools necessitates the creation of interfaces between the online platform and existing Python-based preprocessing software. - Artificial Intelligence and Signal and Image Processing, Biomechanical Engineering, Computational Biology and Bioinformatics, Medical and Health Sciences, Programming Languages, Software Engineering
- Bachelor Thesis, Course Project, ETH for Development (ETH4D) (ETHZ), IDEA League Student Grant (IDL), Internship, Master Thesis, Semester Project
| This project aims to develop a pipeline to register 2D histological images to 3D micro-CT images. - Biomedical Engineering, Computational Biology and Bioinformatics, Computer Hardware, Interdisciplinary Engineering, Materials Engineering, Mathematical Sciences, Mathematical Software, Mechanical and Industrial Engineering, Medical and Health Sciences
- Bachelor Thesis, Internship, Master Thesis, Semester Project
| We seek a highly motivated Bachelor's or Master's student dedicated to developing and applying a mathematical model, simulation, optimization, and process control to deepen the scale-up of bone organoids. This project offers an opportunity to gain valuable work experience within a highly interdisciplinary and international team. - Differential, Difference and Integral Equations, Dynamical Systems, Modeling and Simulation, Optimisation, Process Control and Simulation, Stochastic Analysis and Modelling, Systems Biology and Networks, Systems Theory and Control
- Bachelor Thesis, IDEA League Student Grant (IDL), Internship, Master Thesis, Semester Project
| Current tissue engineering strategies fail to recreate the complex bone architecture where a 3D bone cell network resides in the cavities for mechano-regulation of bone remodeling. This project aims to create a 3D printed in vitro model of bone for medicine. - Biochemistry and Cell Biology, Biomaterials, Interdisciplinary Engineering, Macromolecular Chemistry, Mechanical and Industrial Engineering, Medical and Health Sciences, Polymers
- Master Thesis
| Laboratory-grown miniature bones (organoids) can facilitate the investigation of the biology in healthy and diseased human bone, thereby replacing animal experiments and providing a mechanistic understanding of bone remodeling. The goal of this research is to establish an in vitro technique for volumetric 3D bioprinting of structurally complex human bone organoids. This bone organoid has the potential to enable studying human bone remodeling in the laboratory without the need for animal models. - Biomaterials, Biotechnology
- Internship, Master Thesis, Semester Project
| 3D in vitro models provide a valuable way to study human biology without using animals. However, these models are primarily based on poorly defined animal-derived hydrogels, such as Matrigel or collagen. This limits our detailed understanding of cell-material interactions in bone development, maintenance, and repair. Importantly, these mechanisms are often disrupted in various bone diseases, highlighting the needs for more advanced in vitro models. - Biochemistry and Cell Biology, Chemistry, Engineering and Technology, Medical and Health Sciences
- Semester Project
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