Modelling the osteoid: A quantitative experimental–mathematical platform for osteocyte network formation and transport

Overview

Project Reference: #4MPQC-NATP3

Preferred Project Start: Late 2026/Early 2027

How does a newly formed bone matrix develop into a mineralised tissue containing a functional osteocyte network, and how does this transformation affect the movement of nutrients and signals?

During bone formation, osteoblasts produce a soft, initially unmineralised extracellular matrix known as osteoid. Some osteoblasts gradually become embedded within this matrix and transition into osteocytes, extending dendritic processes that connect them into an intricate three-dimensional network. As the osteoid matures and mineralises, its architecture, mechanics and transport properties also change.

These processes are fundamental to bone formation and function but remain difficult to observe and isolate within native bone. In particular, we do not yet understand how osteoblast movement and embedment, osteocyte dendrite growth, network connectivity and matrix mineralisation interact to create an effective transport system within forming bone.

This project will combine advanced 3D bioengineered osteoid models, quantitative imaging and mathematical modelling. Experimentally tractable and optically accessible models will allow the developing matrix, cells, dendrites and mineral distribution to be mapped at selected time points. These data will inform computational models of osteoid formation, osteocyte network development and the transport of molecules through the evolving microenvironment.

The precise model system, experimental perturbations, imaging approaches and mathematical framework will be refined with the successful student, providing substantial scope for them to contribute ideas and shape the direction of the PhD.

Research activities

This project is part of the Network Architecture and Transport Properties of ECMs Research Theme of the Max Planck Queensland Centre for the Materials Science of Extracellular Matrices (MPQC). It is also connected to the Centre for Biomedical Technologies and a broader Australian Research Council-supported research program titled Engineered Osteocyte Microenvironments.

The student will be based on Level 3 of the Translational Research Institute in Woolloongabba, Queensland, Australia, and will join the Bone & Tumour Bioengineering Research Group led by Associate Professor Nathalie Bock. The project will include mathematical and computational supervision from Associate Professor Pascal Buenzli at QUT and international supervision from Dr Richard Weinkamer at the Max Planck Institute of Colloids and Interfaces in Potsdam, Germany.

The student will contribute to activities that may include:

• Developing and characterising 3D bioengineered models of forming osteoid
• Acquiring 3D images at selected stages of matrix formation and mineralisation
• Quantifying cell movement, osteoblast embedment, dendrite growth and osteocyte network connectivity
• Experimentally measuring transport through the evolving extracellular matrix
• Developing and validating mathematical models of osteoid formation, network development and transport

• Investigating how changes in ECM architecture and mineralisation influence network function.

Skills, techniques and other learning opportunities offered

• 3D osteoid and osteocyte model development
• Hydrogel and extracellular matrix biofabrication
• Extracellular matrix formation and mineralisation assays
• Mechanical, structural and transport characterisation of biomaterials
• Live-cell, fluorescence and confocal microscopy
• Longitudinal and time-resolved 3D imaging
• Fluorescent tracer and diffusion-based transport measurements
• 3D image segmentation, skeletonisation and network reconstruction
• Quantitative analysis of cell positions, dendrites and network connectivity
• Programming and quantitative data analysis using Python, MATLAB or related tools
• Mathematical modelling of cell movement, embedment and network growth
• Network, reaction–diffusion and continuum modelling approaches
• Model parameterisation, sensitivity analysis and experimental validation
• Opportunities to work across biomedical science, materials science, applied mathematics and biophysics
• International collaboration with researchers at the Max Planck Institute of Colloids and Interfaces

Outcomes

This project aims to establish a quantitative experimental–mathematical platform for investigating how the osteoid develops into a mineralised, interconnected osteocyte microenvironment.

The research will determine how cell behaviour, dendrite formation, network architecture and ECM mineralisation evolve together during osteoid maturation. It will also reveal how these changes influence the transport of nutrients, ions, signalling molecules or other relevant solutes through the developing matrix.

The mathematical models will help explain experimental observations and estimate properties that cannot easily be measured directly. They will also be used to predict how altering factors such as matrix composition, mineralisation, cell density or network organisation changes transport within the osteoid.

The project will generate new fundamental understanding of bone formation while establishing a predictive platform that could support future research into bone repair, adaptation, ageing and disease.

High-quality publications will be expected from this project (Bock et al., Prog Mater Sci). Travel to national and international conferences and to the Max Planck Institute of Colloids and Interfaces in Germany, will be available to the successful candidate.

Skills and experience

This project would suit a student with a background or strong interest in Applied Mathematics, Biophysics, Computational Science, Biomedical Engineering, Mechanical Engineering, Materials Science, Biomaterials, Quantitative Cell Biology or a related discipline.

The project can be shaped to suit either a quantitatively trained experimental researcher or a computational candidate with a strong interest in engaging with biological experiments and imaging data. Candidates are not expected to already be experts in both areas.

Desirable qualifications and experience

• A Master of Science or equivalent qualification with a significant research component in Applied Mathematics, Biophysics, Computational Science, Biomedical or Mechanical Engineering, Materials Science, Quantitative Biology or a related field
• Relevant computational, quantitative imaging or laboratory research experience
• Experience with scientific programming or quantitative data analysis
• Capacity to undertake the PhD on a full-time basis

• At least one publication in a peer-reviewed scientific journal.

The ideal candidate will:

• Be highly motivated to undertake about interdisciplinary research spanning experimental biology, bioengineering and mathematical modelling
• Be interested in learning techniques outside their original discipline
• Demonstrate curiosity and creativity when developing models and designing experiments
• Be self-motivated and able to plan and prioritise experimental work
• Have strong analytical and problem-solving skills
• Be able to work both independently and as part of a multidisciplinary and internationally connected team
• Have effective written and verbal communication skills.

Eligibility details

This is a full-time PhD scholarship project. Australian and international applicants are eligible to apply. Applicants must meet QUT’s entry requirements for admission to the Doctor of Philosophy, including the applicable English-language requirements. Read more here about entry requirements.

How to apply

Step 1

Submit your application to n.bock@qut.edu.au with the following subject: ‘PhD–#4MPQC-NATP3–Your Surname’.

Your application must include:

• A cover letter by the applicant (maximum 1 page)
• An up-to-date CV indicating previous lab experience and skills and the details of two referees (including their email addresses)
• Academic transcript

Shortlisted applicants will be invited to an interview.

Step 2

The preferred candidate will be supported to submit a formal expression of interest through the QUT research degree application process. Applicants should review QUT’s research degree entry requirements and application guidance here before applying.

What you receive

• A full-time, tax-exempt stipend of $37,010 per annum, indexed annually
• Scholarship support for a maximum of 3.5 years for a PhD or 1.75 years for an MPhil, including any approved extension
• A possible $5,000 top-up scholarship for an outstanding candidate, subject to eligibility and funding conditions
• Tuition fee sponsorship for eligible international students
• Single Overseas Student Health Cover for eligible international students
• The opportunity to join QUT, the University for the Real World, and undertake research within the advanced multidisciplinary environment of the Translational Research Institute (TRI)
• A dedicated research environment within the Bone & Tumour Bioengineering Research Group at TRI
• Access to advanced biofabrication, microscopy, image-analysis, materials-characterisation and computational facilities
• Supervision and training across biomedical science, applied mathematics, biophysics, materials science and computational modelling
• Membership of the international research centre from the Max Planck Society (MPQC), connected to the Max Planck Institute of Colloids and Interfaces (MPICI)
• Possibility of research exchanges at MPICI in Potsdam, Germany
• Opportunities to participate in multidisciplinary research networks through QUT TRI, CBT and MPQC

Keywords

• Osteoid
• Osteocyte
• Extracellular Matrix
• Mineralisation
• Reaction–Diffusion
• Mathematical Modelling
• Biomaterials
• Bone Formation
• Biophysics
• Bone Tissue Engineering

Contact

Contact Associate Professor Nathalie Bock for more information.