Mangum laboratory: Proteomics and calcium biology

Research Overview

This research laboratory, located in the Department of Pharmacology and Therapeutics (School of Biomedical Sciences), is a central component of our translational research and education enterprise based at the Royal Children's Hospital (hosted by Department of Paediatrics, Melbourne Medical School). An overview of this pioneering translational context can be gained from the following websites.

Luke has chalky teeth (see TV bulletin), and Vidal's research (Kids, family and scientist ) ultimately aims to prevent this common and costly problem. Image copyright The D3 Group

Our Biology

Cell Signalling

The mechanisms used to relay messages within cells are of intense biomedical interest. Complex signalling pathways underlie normal development and health of cells. Many diseases are associated with cell-signalling anomalies. Numerous drugs target the principal signalling effectors, calcium and protein phosphorylation.

Calcium biology

Calcium has many roles inside and outside cells necessitating strict regulation at different concentrations in various locations. Calcium signals are transmitted through cells as transient increases of calcium which normally is kept at a very low concentration in the cytosol (cellular fluid). Cellular toxicity arises if these calcium elevations are too large or frequent (calcium cytotoxicity). It is clear that excess calcium can lead to cell death but disease-related disruptions of calcium signalling are not well understood. How calcium is transported in bulk across epithelia without causing cytotoxicity is a key area requiring pathomechanistic elucidation.

Dental enamel cells

We initiated investigations of calcium handling in enamel cells questioning how they make such a highly-calcified product (tooth enamel is 40% calcium) without suffering the cytotoxic effects of excess intracellular calcium. Of broader biomedical value, this research model comprises epithelial cells that have an informatively elongate morphology and undergo functionally-distinct phases of development linked to production of a hypermineralized extracellular matrix. Dentally, these cells are also central to the understanding of enamel mineralization and associated developmental defects.

For more information - see "Why Enamel Cells" (PDF, 324 KB)

Current research focus

(follow links to see allied Projects and Publications)

  • calcium handling and avoidance of calcium cytotoxicity during mineralization of enamel
  • cause, treatment and prevention of enamel defects, particularly "chalky molars" (Molar Hypomineralisation)
  • function of calbindins (calcium-binding proteins) in health and disease
  • role of ERp29 (a novel protein in the Endoplasmic Reticulum) in ER pathobiology

Our Research Technologies

Molecular and cellular biology

We are using a broad range of experimental approaches from the DNA level (eg cDNA cloning, qPCR) through protein (eg 2-D gels, recombinant protein engineering), cellular (eg confocal and transmission electron microscopy) and physiological levels (eg knockout mouse characterisation).

Proteomics and protein biochemistry

Our speciality is microscale protein biochemistry, a challenging area necessitated by the scarcity of enamel cells. Approaches include mass spectrometry, Edman analysis, amino acid composition, gel electrophoresis and the purification, biophysical and functional analysis of proteins.

An online database (ToothPrint) of dental proteins in rat has been established.

Hard tissue microanalysis

We phenotypically characterise mouse, rat and human teeth using a variety of approaches including polarised light and scanning electron microscopy, histology, micro-CT and microradiography, microhardness and quantitative fracture analysis.

Our Translational Research and Education

Oral and facial sciences

Our laboratory serves as a research hub for the Melbourne Research Unit for Facial Disorders, a medico-dental translational network based at Royal Children's Hospital of Melbourne. By hosting students and practitioners from medical and dental fields, we blend their clinical understanding with our basic science expertise to provide a strong translational platform for cross-disciplinary research and training. Learn more here.

Developmental Dental Defects (D3s, "chalky teeth")

To provide a much-needed hub for research and education about Developmental Dental Defects (DDDs = D3s), we instigated a world-first cross-sector network (The D3 Group; D3G). Research from our lab and elsewhere ("Tooth science") has been embedded throughout D3G's online education resource, supporting a public awareness campaign about the need for research into the prevention of the commonest type of "chalky teeth" (Molar Hypomineralisation). Learn more here.

Proteomics and metabolomics

To amalgamate proteomic and metabolomic interests in Victoria, we instigated a pioneering cross-sector network (Proteomics and Metabolomics Victoria). Learn more here.

Commercialisation

We have patented a novel detector for porous hydroxyapatite that has potential applications in preventive and restorative dentistry. This invention has been spun out to a startup company for further R&D.

Staff

Professor Mike Hubbard

Research Publications

Please see publication lists under each Project:

Calcium handling

Enamel defects

Calbindins

ERp29