MRes - Contribution of acidosis to chronic pain in Paget’s disease of bone

Supervisors: Prof Chantal Chenu (Royal Veterinary College) and Prof Shafaq Sikandar (QMUL) 

Department: Comparative Biomedical Sciences, Royal Veterinary College

Project Details

Paget’s disease of bone (PDB) is a common metabolic bone disorder, characterized by increase bone turnover and giant cells (osteoclasts) responsible for the destruction of the bone (1). The most frequent complication is bone pain. This project will investigate if the increased acidification of the bone tissue due to excessive osteoclast action and inflammation that occur in PDB may contribute to the pain experienced by the patients. We hypothesize that acid-sensing ion channels (ASICs) are activated by the tissue acidosis in PDB (2) and contribute to its associated pain. 

This proposal will use a mouse model of PDB (3) to 1) examine if expression levels of ASICs in dorsal root ganglia and bone are upregulated in Pagetic mice compared to Wild Type (WT) mice using qPCR analysis; 2) measure nerve markers expression in spinal cord and DRGs of 14 months-old WT and Pagetic mice using immunocytochemistry; 3) perform Calcium imaging of primary sensory neurons in culture from either p62p394L +/+ or wildtype mice. This will allow us to visualize neuronal activity under fluorescence microscopy, when perfused with ASIC inhibitors. 

This project is funded by the Paget’s association and is part of a larger work aiming at improving our understanding of the mechanisms of pain in PDB. 

References

  1. Gennari L, Rendina D, Falchetti A, Merlotti D. Paget’s disease of bone. Calcif Tissue Int 2019; 104:483

  2. Abdelhamid RE and Sluka KA ASICs mediate pain and inflammation in musculoskeletal diseases. Physiology. 20015; 30:449.

  3. Daroszewska A, van’t Hof RJ, Rojas JA, Layfield R, Landao-Basonga E, Rose L, Rose K, Ralston SH. A point mutation in the ubiquitin-associated domain of SQSMT1 is sufficient to cause a Paget’s disease-liked disorder in mice. Hum Mol Gen. 2011; 20:2734. 

Requirements

Essential:

  • Must meet our standard MRes entry requirements.
  • Highly motivated student with a relevant First Class or upper Second Class University honours Degree in Biological Sciences, Veterinary or Medicine.
  • English language proficiency and good general communication skills.
  • Good data analysis and problem-solving skills.
  • Organising skills and ability to meet deadlines and to prioritise.
  • Ability to liaise with members of the research group. 

Desirable:

  • Experience in bone biology and/or chronic pain research will be an advantage
  • Experience in histology and qPCR technique 

This is a full-time project commencing in October 2024, based at RVC's Camden campus. 

The Pagetic mice are available. All the ethics and project license are in place. The candidate for this project will only work on mouse tissues and cells and therefore will not need a personal animal license.  

Funding

Partially funded: The lab will be covering the project costs, with the MRes student expected to meet the course fees and their living expenses. 

International applicants are welcome to apply but must be able to fund the difference between "Home" and "Overseas" tuition fees. Please note that EU/EEA and Swiss national students may no longer be eligible for the “Home” rate of tuition fees, dependent on personal circumstances (including immigration status and residence history in the UK) and UK government rules which are currently being developed. For up-to-date information on fees for EU/EEA and Swiss national students following Brexit please see our fees and funding page. 

How to Apply

For more information on the application process and English Language requirements see How to Apply.

Deadline: Sunday 14th July 2024

We welcome informal enquiries - these should be directed to Prof Chantal Chenu (cchenu@rvc.ac.uk)

Interview date and location: TBC

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