A University of Queensland research group has isolated and sequenced a gene precursor thought to play an important role in a number of scaly skin diseases, and may indeed be the skin's natural moisturiser.
The University's Skin Research Group is studying the normal expression of, and genetic mutations in filaggrin - a multi-functional protein found in the outer layer of the skin.
Researchers believe these mutations could be involved in a very common scaly skin disease Ichthyosis Vulgaris which affects one in 3000 people.
This genetically-inherited disease varies remarkably in patients, from dry skin to severe scaliness, reducing the quality of life. Patients with this disorder produce little or no filaggrin.
Wellcome Trust senior research fellow Dr Joe Rothnagel said only a few research groups internationally had studied filaggrin since it was first observed by U.S. researchers in living tissue in the 1970s.
The University of Queensland group is the only group in Australia specialising in the protein, which has also been implicated in other disorders.
Dr Rothnagel said it was known that people with atopic skin (eczema) had reduced filaggrin expression. Auto-antibodies against filaggrin had also been found in people with rheumatoid arthritis.
The filaggrin protein is essentially found in two places, the outer granular layer of the skin; and in the tongue, a complex organ which also expresses many proteins found in the skin and hair.
Dr Rothnagel's research group in the University's Biochemistry Department has attracted Wellcome Trust funding of almost $1 million over five years to expand knowledge of filaggrin and other skin proteins in a complex project with multiple research avenues.
He said the Wellcome Trust's investment in these studies signalled the Trust's belief in the importance of expanding skin biology research in Australia to an international level.
Filaggrin is derived from a large precursor protein. In the past two years the researchers have isolated the gene encoding the precursor in mice, work which may well answer questions on the role of filaggrin in the mammalian skin.
'The mouse gene contains about 16,000 base pairs with a simple structure of three exons and two introns,' Dr Rothnagel said.
The researchers proposed removing the gene encoding filaggrin to see if their models developed dry skin or if their immunological properties were altered in any way.
They have made a targeting vector for filaggrin, and will use new gene transfer technology to remove the filaggrin gene from mice.
A key question they wish to solve is whether skin problems are caused by mutations in filaggrin itself or by mutations in the enzymes involved in modifying the precursor to liberate filaggrin.
The project also will look at families with dry skin conditions to see if it is possible to map disorders in human chromosomes. In the long term, effective gene therapy to overcome such conditions might be developed.
Dr Rothnagel is a University of Adelaide graduate, obtaining a bachelor of science in 1979, honours in 1980, and a PhD in 1986 for studies of the protein in the hair follicle, trichohyalin.
He joined the National Institutes of Health in Bethesda, Maryland, working on mouse filaggrin from 1985 to 1988 when he transferred to Baylor College of Medicine as an assistant professor, conducting transgenic work on keratins and identifying mutations in keratin in human skin diseases.
Dr Rothnagel took up a Wellcome senior research fellowship at the University of Queensland in 1995, with joint appointments as a lecturer in the Biochemistry Department, the Centre for Molecular and Cellular Biology, the Department of Medicine and the Centre for Immunology and Cancer Research.
He heads a skin research laboratory including postdoctoral fellows Dr Donna Mahoney, Dr Xui Qing Wang and Dr Dana Zhang; PhDs Lexie Friend and Pawel Listwan; masters student Betsy Hung, honours students Cameron World, Natalie Chang and Mary Wang; and research assistants Monica Kessler and Seetha Karunaratne.
For further information, contact Dr Rothnagel, telephone 07 3365 4629 or 3365 4625 [Laboratory]; email: josephr@biosci.uq.edu.au
