Intervertebral Disc Degeneration in Short-legged Dogs – Understanding Chemical and Structural Changes using Computational Methods

About the Project

Intervertebral disc herniation (IVDH) has been recognised in chondrodystrophic dogs (short-legged dogs such as Dachshunds, Welsh Corgis and West Highland Terriers) since at least the 1880s, but only in recent years has the genetic basis of this predisposition been confirmed. In these animals, their intervertebral discs, usually spongey, high water-content structures providing cushioning and shock absorbance during normal movement, gradually become stiffer, dehydrated and increasingly solidified until, ultimately, this calcified central part of the disc (nucleus pulposus) can rupture through a tear in the outer, fibrous rim (annulus fibrosus) with potentially catastrophic and often fatal consequences. The herniation causes compression and contusion of the spinal cord, which can cause severe pain and, in some cases, irreversible paralysis. This is an extremely distressing disease for dogs and owners alike, but it is also expensive to treat, with some animals requiring surgery and, unfortunately, it has a relatively high recurrence rate of up to 20%. Furthermore, human lumbar disc herniation manifests in a very similar way, and these data will provide an excellent model for the human condition. We would hope to see this work translated into the human sphere, improving treatments, and reducing economic productivity loss across society, which currently is very high due to large numbers of sick days taken every year.

In this project we aim to understand the fundamental chemical and microstructural changes in the disc as the disease progresses, and ultimately use these data as a starting point for the development of new treatments to retard or reverse crystallization of the disc. We will use molecular dynamic simulations at (canine) body temperature to understand the molecular interactions that occur in the centre of the intervertebral disc, between the growing mineral phase and the native organic molecules (proteoglycans, collagen). To make the models as realistic as possible, we will integrate data obtained from samples of disc material removed during life-saving surgery on canines carried out at The Queen’s Veterinary School Hospital (University of Cambridge), which have been analysed to pinpoint the composition, levels of crystallization present, stiffness and density. This integration of, and comparison with, experimental data obtained directly from diseased animal tissue, will provide increased interpretability.

The project will be based at the University of Leeds, and will be entirely computational. However, there will be close collaboration with Professor Paul Freeman, Principal Clinical Neurologist, at the Department of Veterinary Medicine (University of Cambridge) and there will be opportunities for visiting the Queen’s Veterinary School Hospital throughout the project.

For information on how to apply, please visit the institution website.

Funding Notes

This is not a funded project, but you can apply for funding separately. Self-funding students are also welcome to apply.

For more information please visit the institution website.