PhD Research Project

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Mechanoadaptation of developing limbs: ‘shaking a leg’

Institution:

University of London

Dept/School/Faculty:

The Royal Veterinary College

PhD Supervisor:

Prof A A Pitsillides

Application Deadline:

No more applications being accepted

Funding Availability:

Funded PhD Project (European/UK Students Only)

PhD Research Project

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Animals can modify the shape and mass of their individual limb bones to accommodate both habitual and new, imposed mechanical forces. This is perhaps best exemplified by the increases in bone mass that are seen in the dominant, serving arm of tennis players versus their non-serving, ball-throwing arm - we term the process by which these changes are achieved mechano-adaptation. If we understood the way such mechano-adaptive increases in bone mass were coordinated, we would be able to mimic them and, thus, alleviate any decreases in bone mass that places specific regions of bones at risk of fracture

Skeletal tissues function is a changing mechanical environment, and adult bone shape and size are adapted to this input. These mechanoadaptive inputs are likely to alter radically during limb development, yet their role in attainment of the skeletal proportionality and architecture necessary for locomotion is undefined. Embryo limbs move spontaneously before osteogenesis and these movements may either impact on the initial stages of bone development or mechanoadaptation may be an acquired characteristic, arising only later in development. We find that the contribution made by movement to the development of skeletal architecture has late onset and that distal bones are more sensitive. This project addresses whether skeletal proportionality relies partly upon specific genes that regulate bone mechanoadaptation.
Differential skeletal proportions match to divergent locomotory habits. Relative limb bone size differs between (mice vs. avian) and within classes (chicken vs. ostrich). One distinguishing feature is the relative length of distal elements; longer in ostrich than chicken, which in turn are longer than in mice. The role of mechanoadaptation in these diverse anatomies is unexplored, and it is possible that elongated distal ostrich elements have greater reliance on embryo movement for the marked differential in their growth. This project evaluates the extent to which movement contributes to proportionality of bones along the limb’s proximal-distal axis.
Foetal programming is essential for correct bone function. We have identified a bone gene signature and several candidates associated with acquisition of mechanoadaptation late in foetal development. Work in this project will also aim to pinpoint roles for candidate mechanoadaptive genes in bone development and thus link gene function to anatomical form.

Funding Notes:

Funded scholarship from the Anatomical Society.

Applicants should hold a 2:1 honours degree or equivalent, or a Masters level degree.

Please see the RVC website for information about our English language requirement:

http://www.rvc.ac.uk/Postgraduate/Info/HowToApply.cfm#lang