Investigation of matrix-mineral interactions of enamel formation in Amelogenesis Imperfecta

Project description

Project Summary

Amelogenesis imperfecta (AI), an inherited enamel biomineralisation defect in quality and quantity of dental enamel, is associated with mutations in genes encoding enamel extracellular matrix proteins (EMP). Amelogenin is the main EMP (90% of all matrix protein) in developing enamel and self-organizes in to polymeric nanospheres that associate with the apatite mineral surfaces and are thought to orientate the growth of enamel crystals. This project will study the interactions between amelogenin and the primary mineral structure of enamel, apatite nano-rods. It will test the hypothesis that mutated amelogenin has a higher affinity for mineral surfaces compared with wild-type protein, resulting in crystal growth inhibition leading to AI. Using recombinant amelogenins, including a known mutation that causes AI in mice, the student will use a combination of physical techniques to explain the effects of the mutation on amelogenin-mineral interactions. Atomic force microscopy (AFM) will be employed to visualise organization of nanospheres with mineral crystals and determine the binding-unbinding forces of the protein on the crystal surfaces. TEM experiments will permit identification of the specific crystallographic faces at which these interactions occur. Data generated will give entirely novel information relevant to AI pathology and the fundamental mechanisms of biomineralisation.

Aims and Objectives

This project will use atomic force microscopy (AFM) to study interactions between wild-type and mutant amelogenins and the enamel crystals themselves. It will test the hypothesis that amelogenin mutations in AI perturb protein-protein and protein-mineral interactions during enamel formation resulting in biomineralisation defects. AFM will be used in imaging and force modes to study amelogenin self assembly ± mutations and to characterise interactions between these proteins and apatite crystals to explain the effects of the mutation on AI pathobiology.

Entry requirements

Please contact our staff for further details about entry requirements.

How to apply (email)

How to apply (phone)

+44 (0)113 343 7497