Despite the significant progress made in research of bone growth during normal development, previous studies have been limited in their ability to investigate local mechanisms of growth recovery after injury (i.e. catch-up growth). This is mainly due to three roadblocks: 1) the current conceptual framework focuses almost exclusively on intrinsic regulation within the bone, disregarding extrinsic regulators; 2) most genetic models affect both limbs at the same time, and thus cannot distinguish between mechanisms that stimulate recovery of only the injured bone vs. systemic bone growth; 3) many genetic models are not reversible, which hampers the study of recovery. Using sophisticated mouse and quail genetic models, we will independently manipulate and monitor the foetal bones and surrounding tissues, addressing their communication upon injury. The main hypothesis is that the intrinsic response to injury initiates the recovery of bone growth, and is then modulated by extrinsic cells and molecules that confer robustness. To test this hypothesis, we have designed an innovative strategy to uncover mechanisms of catch-up growth via the following aims: 1) Determine the identity and role of stress signals in bone catch-up growth; 2) Trace and determine the role of external progenitor cells in bone catch-up growth. 3) Study the control of bone catch-up growth by negative feedback. Together, these aims will converge into a new framework for understanding bone catch-up growth, which will generate new fundamental knowledge about the cells and signalling molecules involved in the foetal response to bone growth impairment. This knowledge could be used to reactivate foetal recovery mechanisms in future therapies, and to help the generation of new diagnostic tools to identify defective processes underlying growth disorders.
Connective tissue growth factor, catch-up growth, limb asymmetry, bone growth, growth plate, genetic models
Australian Regenerative Medicine Institute (ARMI)
Masters by research
Top-up scholarship funding available
15 Innovation Walk