Job description
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.
Requirements
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.
Conditions of employment
You will be employed by Amsterdam UMC Research BV.
A 12-month contract, with the intention of extending the contract for an additional 12 months.
Classification in salary scale 10: € 3.724 to € 5.867 gross for full-time employment (depending on experience). In addition to a good basic salary, we offer 8.3% end-of-year bonus. Calculate your net salary here.
Holiday hours: 194.4 per year for full time and a possibility to save additional hours.
100% reimbursement for public transport travel costs. If you travel by foot, bicycle, or car, a mileage allowance of €0.21 per km applies (up to a maximum of 40 km one way by car).
Do you prefer walking or cycling? Take advantage of our good bike scheme.
Pension accrual with BeFrank, a modern, comprehensible and fairly priced pension.
Watch this video with more information about joining Amsterdam UMC Research BV.
Employer
Amsterdam UMC
You will join the Laboratory Specialized Diagnostics and Research, Bone and Calcium Unit at Amsterdam UMC, location VUmc. The unit is led by Dr. Nathalie Bravenboer and has extensive expertise in bone biology, tissue explant models and rare metabolic bone diseases. The laboratory is also closely connected to clinical care for people with Osteogenesis Imperfecta and other bone disorders.
You will work within the TKI project Osteogenesis Imperfecta organ-on-chip Models for Pre-Clinical Testing (OImpact). Amsterdam UMC collaborates closely with the University of Twente, which co-develops the BBoC device and mechanical actuation platform; Azafaros, a pharmaceutical SME providing and co-developing OI-relevant compounds; and Proefdiervrij, a non-profit partner promoting animal-free research.
The project brings together clinical, biological and technological expertise. This multidisciplinary setting gives you the opportunity to connect laboratory research with clinical questions and contribute to the development of new approaches for people with a rare bone disease.
Amsterdam UMC Research BV
Amsterdam UMC Research BV supports non-profit scientific research. In doing so, we provide researchers with everything they need to excel. Our principal investigators (PIs) and project leaders offer support in the field of project management, finance and human resources. In medical scientific research projects, legal support is also provided.
Watch the video to find out more.
Additional information
During the publication period, applications will be handled continuously. If the vacancy is filled, it will be closed prematurely.
The selection process involves a joint selection committee with a colleague from the University of Twente. Your application may therefore also be accessed by the University of Twente colleague as part of the interview process.
If you would like more information, please feel free to contact dr. Nathalie Bravenboer, Bone and Calcium Unit, LGDO, Amsterdam UMC, at n.bravenboer@amsterdamumc.nl.
A reference check, screening and hiring assessment may be part of the procedure. Read here whether that applies to you. If you join us, we ask you for a VOG (Certificate of Good Conduct).
Internal candidates will be given priority over external candidates in case of equal suitability.
Acquisition in response to this vacancy will not be considered.
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