Pain Phenotype Characterisation in Preclinical Models of Osteoarthritis

Summary

Osteoarthritis (OA) is the most common chronic joint disease, affecting 15% of the population and causing a significant socioeconomic burden. It is a debilitating condition characterised by degeneration of joint tissues, chronic joint dysfunction, severe pain and loss of mobility. Pre-clinical animal models form the foundation of the translational drug-discovery pathway for complex diseases like OA, where multiple disease phenotypes exist. A plethora of animal models have been developed to study disease mechanisms, identify biological targets and test potential therapies. Yet OA continues to be one of the major causes of chronic pain and disability with no effective treatments. This lack of 'translation' puts into question how well pre-clinical animal models predict outcomes in people. Human OA is a heterogenous disease with a number of sub-types. Similarly, animal models represent different 'phenotypes' of OA. To improve translation of pre-clinical findings, better characterisation of these OA animal models is required, so they can be mapped to different sub-types of the disease in humans. This project aims to characterise the pain phenotype of two mouse models of knee OA currently used in pre-clinical research. Pain behaviour and changes in the peripheral nervous system will be measured at different stages of disease progression, and these will be mapped to joint tissue pathology.

Supervisor(s)

Dr Sanaa Zaki

Research Location

Sydney School of Veterinary Science

Program Type

PHD

Synopsis

This project will combine a novel technique for evaluating neuronal injury with established pain behaviour assays and molecular biology techniques, to characterise the pain phenotype of established mouse models of knee osteoarthritis (OA). The findings will build on our previous work looking at the predictive utility of animal models of OA, to inform future animal model selection for preclinical testing of OA therapies. Through the course of the candidature the student will have the opportunity to learn many experimental skills including surgical and mechanical techniques for inducing OA in mice, pain behaviour analysis, histology and immunohistology, electron microscopy, molecular biology, protein analysis and, cell and tissue culture.

Additional Information

The Translational Orthopaedic Pain Investigation Centre (TOPIC) is a newly established centre located within the Kolling Institute, forming part of the Institute of Bone and Joint Research. TOPIC is a joint collaboration between Raymond Purves Bone and Joint Research Laboratories and the Sydney School of Veterinary Science. Its primary purpose is to investigate osteoarthritis pain. The group is currently working on understanding the relationship between joint disease and pain, as well as the predictive utility of animal models used to study OA pain. The centre has established standardised methods for measuring pain and disability outcomes in commonly used pre-clinical animal models. As part of TOPIC and the Kolling Institute, the student will have access to state-of-the-art molecular biology, histology, imaging and behaviour testing facilities. Through the course of the candidature the student will have the opportunity to learn many experimental skills including surgical and mechanical techniques for inducing OA in mouse models, pain behaviour analysis, histology and immunohistology, electron microscopy, molecular biology, protein analysis and, cell and tissue culture. This project would suit a highly motivated BSc with honors, or DVM graduate with some research and basic laboratory experience, and an interest in translational health related research. The Project is available as a full-time candidature with funding available from the host laboratories for the first year (a stipend paid at standard RTP rates). However, the student is expected to apply for RTP/UPA and other scholarships for subsequent years.
Additional supervisor Professor Christopher Little 

HDR Inherent Requirements

In addition to the academic requirements set out in the Science Postgraduate Handbook, you may be required to satisfy a number of inherent requirements to complete this degree. Example of inherent requirement may include:

- Confidential disclosure and registration of a disability that may hinder your performance in your degree;
- Confidential disclosure of a pre-existing or current medical condition that may hinder your performance in your degree (e.g. heart disease, pace-maker, significant immune suppression, diabetes, vertigo, etc.);
- Ability to perform independently and/or with minimal supervision;
- Ability to undertake certain physical tasks (e.g. heavy lifting);
- Ability to undertake observatory, sensory and communication tasks;
- Ability to spend time at remote sites (e.g. One Tree Island, Narrabri and Camden);
- Ability to work in confined spaces or at heights;
- Ability to operate heavy machinery (e.g. farming equipment);
- Hold or acquire an Australian driver’s licence;
- Hold a current scuba diving license;
- Hold a current Working with Children Check;
- Meet initial and ongoing immunisation requirements (e.g. Q-Fever, Vaccinia virus, Hepatitis, etc.)

You must consult with your nominated supervisor regarding any identified inherent requirements before completing your application.

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Keywords

osteoarthritis, arthritis, Pain, animal, Models, Musculoskeletal, inflammation biomedical, knee joint, histopathology, cartilage, neurophysiology, Ageing

Opportunity ID

The opportunity ID for this research opportunity is: 2657