PhD: Exploring joint mechanics and the relationship between shape, strain and cellular behavior through life

Joints are a vital component of locomotion and feeding in all vertebrates. Joint pathologies are frequently seen during
ageing, both in humans (a majority of people over 65 have osteoarthritis in at least one joint) and in most if not all
vertebrate species, including pets, working animals and animals in the wild, significantly impacting mobility and quality
of life. While we have a good understanding of the signalling required to initiate joint development, our understanding
of how local mechanical and genetic cues shape the joint throughout the lifecourse is incomplete, but better
understanding of this could help us improve joint health during ageing.
In this project we will build the first experimentally validated computational models of joint mechanobiology through
the whole lifespan of a vertebrate, the zebrafish. To do this we will generate Finite Element models of wild type fish
at key stages throughout their life to capture the mechanical performance of joints during development, maturity and
ultimately ageing. This will be achieved by segmenting bone, cartilage, muscle and soft tissue data from micro
computed tomography images of the joint of larval, juvenile, adult and aged zebrafish. We will collect 3 dimensional
shape data, along with strain data from muscles to inform on jaw loading. We will validate these data with real data
acquired from high speed videos of joint movement in zebrafish. The student will then test the relative impact of
shape and material properties on joint strain in ageing wild type fish and those carrying joint mutations that are also
seen in human populations. A major advantage of Finite Element Analysis (FEA) is the potential to isolate the effects
of specific properties on the biomechanics of a biological system. Material properties obtained from different strains
can be arbitrarily assigned and stochastically changed between FE models to quantify the effect of material properties
on a particular FEA simulation. Material properties can be swapped between comparative models that significantly
differ in shape in order to isolate the effect of morphology from those of material properties, on joint strain and
function. These simulations can provide novel information regarding the impact of shape versus properties on the
biomechanical performance of the joint, and give insight into why some mutants develop different pathologies. We
can then test how to manipulate joint performance in silico.