Postdoc OIMPACT Bone and Calcium Research

In this Postdoc position, you will investigate bone remodelling and fracture healing in a rare genetic bone disorder, Osteogenesis Imperfecta (OI), using a human-relevant organ-on-chip model.

OI is an inherited connective tissue disease characterised by low bone mass, increased bone fragility and frequent fractures, often after very minor trauma. OI is caused by mutations in the genes encoding type I collagen, a key structural protein in bone. These mutations lead to abnormal collagen quantity or quality, resulting in thin, porous and poorly organised bone.

People with OI can experience recurrent fractures, deformities of the long bones and spine, short stature, pain and reduced mobility. Current treatments mainly increase bone mass by inhibiting bone resorption. However, these treatments do not sufficiently restore bone quality or fracture healing, and there is currently no curative therapy.

Within this project, you will use the broken-bone-on-chip (BBoC) model to study how human OI bone remodels and heals under controlled in vitro conditions. In the first phase, you will validate and implement the BBoC technology. In the translational phase, you will study how a candidate pharmaceutical compound influences bone remodelling and fracture healing in the OI-BBoC model.

Your work aims to demonstrate that this human organ-on-chip platform can serve as a reliable measurement model to understand OI pathology and predict therapeutic effects on bone remodelling and fracture healing. Ultimately, your research can contribute to the development of better treatments for people with OI.

Your work starts with the biology inside the chip. Using human bone explants and cells, you will optimise the BBoC model for studying bone remodelling, with a particular focus on osteoclasts and their interaction with osteoblasts.

As the model develops, you will:

• enhance and stabilise the presence of osteoclasts in the system and establish reliable osteoblast–osteoclast communication within the chip;
• design and refine culture conditions, loading schemes and biological read-outs to capture key processes of bone resorption and formation;
• implement and validate the BBoC platform within the Amsterdam UMC Bone and Calcium Unit, using bone tissue from people with OI and healthy donors;
• characterise fracture healing and bone turnover by analysing cell migration, matrix deposition and collagen I remodelling, alongside soluble markers of bone formation and resorption;
• design and perform preclinical experiments with a pharmaceutical compound provided by our industrial partner, Azafaros, including dose-finding, longitudinal read-outs and comparison with current clinical standards.

You will repeatedly sample perfusates for markers such as ALP and P1NP and work closely with colleagues on advanced analyses, including proteomic profiling. Once the model is robust and benchmarked in our setting, you will focus on its core translational goal: testing a pharmaceutical compound in the OI-BBoC model.

Throughout the project, you will work closely with clinicians, basic scientists and engineers. You will play an important role in translating a sophisticated organ-on-chip device into a practical human measurement model that can support future OI therapy development.

We are looking for a candidate who combines strong experimental skills with an interest in bone biology and translational research. You have:

• a PhD in biomedical sciences, bio-engineering, (molecular) medicine or a closely related field;
• solid experience with advanced cell culture; experience with primary human cells and/or bone or other tissue explants is a strong advantage;
• an affinity with bone biology and bone remodelling, including osteoblasts and osteoclasts, or a clear motivation to specialise in this area;
• experience with biological read-outs, such as RT-PCR, imaging, immunocytochemistry or histology; experience with organ-on-chip or microfluidic models is an asset;
• strong experimental planning and troubleshooting skills, with the ability to carefully standardise and document protocols.

You communicate fluently in spoken and written English and work proactively in a multidisciplinary environment. Experience with osteoclast differentiation or assays, co-culture systems or pharmacological testing in complex in vitro models is an additional advantage.