Research in the Laboratory of Skeletal Cell Biology and Physiology (SCEBP Lab, led by Prof Dr Christa Maes) focuses on the molecular and genetic control of skeletal stem cells and progenitors for bone-forming osteoblasts [1, 2], with special interests in how they function to mediate bone homeostasis and fracture repair [3], how they associate and crosstalk with the vasculature and the hematopoietic cells of the bone marrow [4], and how they interplay with other tissues and contribute to the regulation of systemic energy metabolism, glucose homeostasis, and the development of obesity and diabetes [5]. By gaining mechanistic insights in skeletal cell biology and physiology we aim to contribute to the development of new treatments for stimulating bone formation and regeneration, which are much needed as bone integrity and regeneration are strongly compromised by ageing, osteoporosis, and metabolic disorders.
Our prime working models are genetically modified mice, including inducible and site-specific mouse mutants and transgenic mice carrying fluorescent reporters for in vivo lineage tracing and cell fate mapping. Specific skeletal cell populations of interest are thereby visualized by advanced deep-tissue 3D imaging methods [6], quantified and isolated by flow cytometry and FACS, and characterized by molecular methods. In our recent previous work, we have studied osteogenic progenitor cells associating with angiogenic blood vessels and characterized the importance of specific molecules and signalling pathways for bone formation during growth, fracture repair, and ageing. We now obtained funding to join forces with the Laboratory for Computational Cancer Biology and Epigenomics at the KU Leuven Department of Oncology, led by Prof Dr Pavlo Lutsik, to deepen our understanding and gain new insights in the regulation and activation of skeletal stem/progenitor cells in health and disease.
References:
1. Melis et al. (2024). Skeletal stem and progenitor cells in bone physiology, ageing and disease. Nat Rev Endocrinol. Doi: 10.1038/s41574-024-01039-y.
2. Trompet et al. (2024). Skeletal stem and progenitor cells in bone development and repair. J Bone Miner Res. Doi: 10.1093/jbmr/zjae069.
3. Böhm et al. (2019). Activation of Skeletal Stem and Progenitor Cells for Bone Regeneration is Driven by PDGFRbeta Signaling. Dev Cell. Doi: 10.1016/j.devcel.2019.08.013.
4. Mesnieres et al. (2021). Fetal hematopoietic stem cell homing is controlled by VEGF regulating the integrity and oxidative status of the stromal-vascular bone marrow niches. Cell Rep. Doi: 10.1016/j.celrep.2021.109618.
5. Dirckx et al. (2018). Vhl deletion in osteoblasts boosts cellular glycolysis and improves global glucose metabolism. J Clin Invest. Doi: 10.1172/JCI97794.
6. Peredo et al. (2022). Visualization and quantification of the stromal-vascular compartment in fetal or adult mouse bones: from sampling to high-resolution 3D image analysis. STAR Protoc (Cell Press). Doi: 10.1016/j.xpro.2022.101222.
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Project
Skeletal stem cells (SSCs) and related progenitors in postnatal bones, collectively termed skeletal stem/progenitor cells (SSPCs), are crucial to provide osteoblasts for bone formation during homeostatic tissue turnover and fracture repair. Besides mediating normal bone physiology, SSPCs also play important roles in various metabolic diseases, including osteoporosis and diabetes. Moreover, loss of proper regulation and aberrant activation and differentiation of SSPCs may cause or contribute to certain bone cancers. Understanding the regulatory cues controlling SSPCs and insights in the changes they undergo with ageing, metabolic disease and tumorigenesis, can help identify targets for osteoanabolic drugs (to treat age- or disease-associated bone loss), bone regenerative medicine, and cancer therapy.
In the currently vacant PhD project, the student will work in this context and employ complementary approaches to decipher specific roles of SSPC populations in the postnatal bone environment, and how they are regulated molecularly. The student will therefore study mice with SSPC-targeted mutations and apply basic bone phenotyping methods, such as micro-/nano-CT, histology and histomorphometry and in vitro approaches, as well as use lineage tracing, advanced high-resolution 3D confocal microscopy and computational image analysis, transcriptomic profiling by single cell and bulk RNA-seq, and multiomics approaches. The work will run in close collaboration with the team of Prof Dr Pavlo Lutsik, which will bring state-of-the-art computational methods to the project and add key expertise for analyzing high-dimensional multiomics-based datasets, that will be implemented into the characterization of SSPC populations and their control mechanisms.
Profile
We are looking for a bright and highly motivated PhD candidate with specialized training in cell and molecular biology, physiology, biochemistry and biomedical research methods. Fitting candidates to join our team 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 training 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 delineate priorities, are required. An eagerness to learn is essential, as is a strong will to gain deep mechanistic understanding of the systems under study and to find answers to important questions in skeletal cell biology.
Candidates should hold a Masters’ degree in a relevant area (e.g., biomedical sciences or engineering) or an equivalent diploma, with minimally a final ‘cum laude’ grade. Skills and experience in mouse genetics or other in vivo work, histology, microscopy, molecular biology and/or (transcript)omics data analysis, is not expected but certainly a plus.
Excellent written and oral communication skills are needed. 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.
Offer
We offer a 4-year PhD position in an international research team, with training and supervision at multiple levels, an exciting project integrating various state-of-the-art techniques, and numerous possibilities to further grow scientifically: by designing and performing research, writing papers as first author, participating in international meetings and courses, collaborating with other scientists, etc. Specifically, we offer:
- A fully funded position for 4 years (pending a positive evaluation after the first year) at KU Leuven. The starting date is flexible and determined with the selected PhD student candidates.
- Prime affiliation and basis in the SCEBP Lab, one of the units of the Skeletal Biology and Engineering Research Center (SBE) in the Department of Development and Regeneration, located on the large Leuven University Hospital & Health Science Campus where basic, translational and clinical research meet.
- Close collaboration with the group of Prof Dr Pavlo Lutsik, Department of Oncology, such that the PhD candidate will benefit from the combined expertise of the two project supervisors and be immersed in vibrant and stimulating scientific environments, with ample possibilities to interact with other researchers and collaboration opportunities within and beyond the two home teams.
- Enrollment in the PhD program of the Biomedical Sciences group at KU Leuven and its Medical School (Doctoral School of Biomedical Sciences).
- KU Leuven is consistently ranked within the top of the world’s and Europe's leading universities, located in the historic and vibrant city of Leuven in the heart of Europe, just 30 km east of Brussels and at less than two hours travel from Paris, London, and Amsterdam. Leuven has a strong international appeal, and English is the working language for research at KU Leuven.
Recent insights in SSPC biology are reviewed here
Interested?
For more information on this project and position, please contact Prof Dr Christa Maes (christa.maes@ kuleuven.be).
To apply for this PhD opportunity, candidates should submit (i) a motivation letter, (ii) a CV including detailed information on study results, mobility and/or research experience, and (iii) the names and contact information of at least 2 professional references.
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