How does the C-terminus of parathyroid hormone-related protein modify intracellular signalling?

Research Opportunity
PhD
Project Status
Future
Department
Medicine and Radiology
Location
St Vincent's Hospital
Supervisor Email Number Webpage
E/Prof TJ Martin Personal web page
A/Prof Natalie Sims Personal web page

Project Details

Parathyroid hormone-related protein (PTHrP) is a paracrine factor produced by many cells within the body including osteoblasts and osteocytes. It is also a produced by breast cancer cells, and contributes to the spread of cancer to the skeleton. PTHrP has an N-terminus that shares sequence homology with parathyroid hormone, and they both act through the same G-coupled receptor, but PTHrP also has domains that are unique, including a nuclear localizing sequence, and a long C-terminal region. The functions of these regions of PTHrP remains unknown, but identifying them could help in understanding how PTHrP acts in both physiological and pathological contexts.

We have carried out RNA-sequencing in osteocytes that express mutated forms of PTHrP, and have found changes in gene regulation specific to the unique regions of PTHrP. This provides new information about the way that PTHrP can signal, not only in osteocytes, but in all cells in which PTHrP is expressed. This project will use cell culture techniques, overexpression studies, and cell-based assays to determine the function of the unique regions of PTHrP in osteocytes and in breast cancer cells.

This project will use cell culture systems, confocal immunofluorescence, molecular biology, reporter assays, and quantitative PCR techniques.

This project is conducted in St Vincent’s Institute of Medical Research, Bone Cell Biology and Disease Unit.


School Research Themes

Musculoskeletal



Research Opportunities

PhD Graduate Research Students who are interested in joining this project will need to consider their elegibility as well as other Graduate Research requirements before contacting the supervisor of this research

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Key Contact

For further information about this research, please contact a supervisor.

Department

Medicine and Radiology

Research Node

St Vincent's Hospital