Determination of the non-coding RNAs in the knee joint tissues of dogs at differing risk to cranial cruciate ligament rupture.

Background: The cranial cruciate ligment (CCL) is the most frequently damaged ligament of the canine knee joint following injuries and age-related ligament breakdown, leading to the development of osteoarthritis (OA). Dogs breeds are at differing risk to cruciate ligament injury with dogs such as the Labrador retriever being at high risk and dogs such as the greyhound being at low risk.

We have identified changes in small molecules (small non-coding RNAs) in low, high risk and diseased CCLs and associated synovial fluid from ex-vivo donated canine knee joints as well as in aged and diseased human anterior cruciate ligaments (ACLs)¹. We have profiled the miRNAs within these dog tissue groups with significant differences being noted in terms of candidate miRNAs that could be used to develop a diagnostic test for cruciate rupture. We have not, however, profiled many of the other non-coding RNAs such as long non-coding RNAs (lncRNAs) and transfer RNAs (tRNAs) which could be also important biomarkers for the diagnosis and treatment of this condition.

This project will profile all non-coding RNAs (sncRNAs) in low, high risk and diseased CCLs and associated synovial fluid from ex-vivo donated canine knee joints to look at possible diagnostic and therapeutic pathways that may help with improved management of cruciate rupture.

Objectives:

1)    Identify and characterise all non-coding RNAs within low, high risk and diseased CCLs and associated synovial fluid.

2)    Use bioinformatic pathways to examine the role of identified candidate non-coding RNAs in cruciate ligament rupture to further develop diagnostic and therapeutic targets.

Our group is multidisciplinary with expertise in both wet laboratory work and computational biology skills. All supervisors are unique in our ‘One Health’ approach to musculoskeletal disease, ageing and RNA as we are fundamental, biomedical and veterinary scientists. These supervisors will apply their skills to both human and animal datasets and tissues and therefore would be able to provide students with an interdisciplinary approach to research, preparing them to meet the challenges inherent in the renewed momentum for ‘One Health’.

Other Training to be given:

As part of their degree registration, the student will have access to the Liverpool Doctoral College and its training resources including lectures on time management, team building, career development as well as thesis writing support and viva practice. Other modules such as study design and statistical training are available through the Department of Biostatistics at Liverpool. The student will be a member of the Comparative Musculoskeletal disease group at the Institute of Life Course and Medical Sciences. This research environment will provide a great opportunity for the PhD student to learn new skills in study design, participate in clinical related research, bioinformatics, data analysis and preparing work for publication.

Applicants will need an undergraduate degree in Biological Sciences or related; 2:1 or equivalent.

Enquiries to: Informal enquiries to Professor Eithne Comerford on ejc@liverpool.ac.uk or Professor Mandy Peffers on peffs@liverpool.ac.uk.

To apply: please send your CV and a covering letter to ejc@liverpool.ac.uk with a copy to ilcamspgradmin@liverpool.ac.uk.