STAT3 signalling and the role of stromal-vascular communication in the development of cortical bone

 

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This is one of two research projects studying anabolic treatments for osteoporosis. Melbourne is the home institution for this project. View the KU Leuven-based partner project.

Please be advised that applications for this project are no longer being accepted

Cortical bone (bone’s outer shell) forms through a process of consolidation, including the closure of blood vessel-impregnated pores. However, it is essential that some vascularised pores remain, to enable egress of bone marrow cells, such as neutrophils, to the circulation. During ageing, these pores within the cortex expand. Although this process is not understood, it is likely to involve communication between stromal cells, which differentiate into bone-forming osteoblasts, and the vasculature. This project seeks to identify how the vasculature and osteoblasts communicate to facilitate the development and degradation of cortical bone, the toughened outer shell of all skeletal elements.

The laboratory of Professor Sims (The University of Melbourne and St. Vincent’s Institute of Medical Research) studies cortical bone development and the processes by which cortical bone degenerates over time. In our previous work, we have developed methods for measuring cortical bone maturation during bone growth, and have established a mouse model with high cortical porosity due to increased JAK-STAT signalling within bone. One of the features we have noted in this model is a high level of vascularisation within the cortex, which could contribute to the high cortical porosity. In the currently vacant PhD position, the student will use this model and a range of image analysis techniques to understand the bone and vascular signalling pathways that drive high cortical porosity.

To determine the specific molecules and cells that contribute to cortical porosity, the student and team will use genetically modified mouse models, including inducible and site-specific mouse mutants, fluorescent cryohistology and light sheet microscopy, and will apply bone phenotyping methods as micro-CT, histomorphometry and high-resolution 3D confocal vascular imaging.

Project goals

The overall aim is to identify the first signalling pathway by which osteoblasts control cortical bone trans-vascularisation, which could ultimately lead to improved or new anabolic treatment approaches for osteoporosis.

Supervision team

The University of Melbourne: Professor Natalie Sims

KU Leuven: Associate Professor Christa Maes

*Click on the researcher's name above to learn more about their publication and grant successes.

Who we are looking for

We are looking for a bright and highly motivated PhD candidate to join our team. Fitting candidates are expected to be very engaged, pro-active and creative, eager to drive their research project, and with good critical-thinking and problem-solving abilities. The work of a PhD student includes designing research protocols, planning and performing experiments (both independently and as part of a team, with thorough training provided by experienced researchers), analyzing data, reporting results to supervisors and colleagues and discussing the findings to shape and outline the next steps. Therefore, good organisational skills, time and project management and ability to work to priorities, are required.

Good knowledge of cell and molecular biology, physiology and the basic biomedical research methodologies is necessary. Fitting candidates will hold a Masters degree in a relevant area (with a final ‘cum laude’ grade), or an equivalent diploma (e.g. Honours degree). Skills and experience in histology, microscopy, molecular biology, transcriptomic data analysis, and/or in vivo work (especially with mice) is not expected but certainly a plus.

Excellent written and oral communication skills are essential. Demonstrated ability to write research reports (e.g., a master thesis) or other manuscripts to a publishable standard (even if not published to date) is expected.

Further details

We offer a PhD position in an international research team, with training and supervision at multiple levels, an interesting project and state-of-the-art techniques, and numerous possibilities to further grow scientifically, including by designing and performing research, writing papers as first author, participating in international meetings, collaborating with other scientists, etc. Specifically:

  • A fully funded position for 4 years, of which one year will be spent in the partner institution, with the aim of obtaining the PhD degree in both institutes.
  • The candidates will be enrolled in the PhD programs of the Biomedical Sciences group at KU Leuven and of the University of Melbourne, Department of Medicine at St Vincent's Hospital.
  • The starting date is flexible and will be determined with the selected PhD student candidates.
  • The PhD candidates will benefit from the combined expertise of the project supervisors at KU Leuven and University of Melbourne, and the embedding into two research environments. The collaboration between Associate Professor Christa Maes and Professor Natalie Sims is designed to build a strong network of researchers interested in the biology of bone health and disease, in which future research work will make use of the resources developed in the current projects for other joint studies, e.g. in models of skeletal disease and repair, cancer and metastasis, and chronic kidney disease.
  • The specific PhD project described here will be based at St. Vincent’s Institute of Medical Research (with a minimum 12-month stay at KU Leuven) and include affiliation to the Melbourne Medical School.
  • The Bone Cell Biology and Disease Unit at St. Vincent’s Institute (SVI) is located within a world class multidisciplinary medical research institute which includes a wide range of medical research specialties, including basic, clinical and translational research. We are located on the campus of St. Vincent’s Hospital, one of Melbourne’s largest teaching hospitals, which is a short walk from both the main campus of The University of Melbourne, and the City of Melbourne.
  • KU Leuven is consistently ranked within the top of Europe's leading universities and English is the working language for research; for more information visit www.kuleuven.be/english/.
  • SVI is located walking distance from the Central Business District of Melbourne, a vibrant multicultural city and one of the “most livable cities” in the world.

For more information on this project please contact Professor Natalie Sims (nsims@svi.edu.au). For information on both projects, contact Professor Maes and Professor Sims.

Please be advised that applications for this project are no longer being accepted

First published on 8 February 2022.

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