Molecular Biotechnology

Overview

Head of Division
Professor Wayne Thomas BSc Hons PhD

Professor Thomas currently holds a Professorship at the University of Western Australia and is a Senior Principal Research Fellow, NHMRC. He has been division head since 1990. He has previously worked at the Medical Research Council, Clinical Research Centre London and at Walter and Eliza Institute for Medical Research. He is the chairman of the International Allergen Nomenclature Committee.

Divisional Summary
Research in the Division of Molecular Biotechnology encompasses studies on the mechanisms of inflammation and allergy and the development of methods to treat or prevent diseases resulting from these processes.

Allergen Group

Advances in medical research are highly dependent on having the right tools for the job. An outstanding problem which encompasses most of work of the Division of Molecular Biotechnology is to determine how immune responses to allergens and other inhaled lead the development of allergy and asthma. While fundamental immunology continues to define the important elements and pathological consequences of activating the immune system most of these result from interactions of receptors with specific antigens and are highly dependent on the doses of the antigens and the context in which they are presented. It is therefore not surprising that studies undertaken with the undefined extracts of allergen sources have produced a myriad of results with little agreement between investigators and little potential for knowledge-based interpretations. The essence of the work of Molecular Biotechnology has been to tackle this disconnect by incorporating both the production of defined allergens and antigens and their use for immunological investigation within the one research group.
The specific research areas have concentrated on 1) determining the immune responses to allergens with varying potency and from different sources to elucidate the differences between responses that lead to allergy and responses that do not, 2) the development of improved immunotherapy with molecularly defined allergens and molecularly engineered derivatives of allergens, and 3) the study of other mucosal immune responses that could influence asthma pathogenesis, especially to microbial antigens.
House dust mite allergy has remained the main focus since it is the most important cause of allergy worldwide and is especially dominant in Australia. New methods of immunotherapy with adjuvants are being explored in mice made allergic to the house dust mite allergen homologue papain. Allergy to cats is being studied because it has been revealed that although the final outcome is an immediate hypersensitivity reaction the sensitisation process is quite different to that of the house dust mite. The study of responses to other mucosal antigens has examined responses to common mucosal colonising bacteria Haemophilus influenzae and Streptococcus pneumoniae and in mice Pasteurella pneumotropica in combination with papain allergy.

Inflammation Group

Members of the Inflammation Research Group are elucidating the mechanisms by which the UVB wavelengths in sunlight can modulate immune responses, particularly those associated with asthma development.  UV exposure is one of the most important environmental factors affecting man.  We know that UV exposure can initiate skin cancers but it is because of a suppressed immune system that these cancers develop and grow and are not immunologically rejected.  The UV-induced suppression of the immune system is systemic and causes reduced responses to allergens delivered to the airways.  The results have been consistent in two models of respiratory airways disease in mice in which UV irradiation of skin reduces some of the hallmark symptoms of asthma.  We have shown that UV-irradiation of skin causes the induction of regulatory cells which when transferred into new mice can modulate immune responses to respiratory allergens.  Extensive studies are ongoing in an attempt to identify and characterise these cells, track them and determine their mode of action.  Studies are also focussing on the immunological potency of vitamin D that is formed in UV-irradiated skin.  As a model we paint the active vitamin D on skin and investigate the immunological consequences.  We have been focussing on CD4+CD25+ cells in the draining lymph nodes.  They have increased activity and gene arrays and functional studies suggest that this is by increased production of interleukin-2.  In other studies we are investigating the effect of UV irradiation of skin on cells in the bone marrow.   Our studies suggest that if we deliver sufficient UV rays to the shaved skin of mice to cause some inflammation (similar to a sunburn), the bone marrow is stimulated to produce altered cells which in turn would be attracted back to the inflamed skin site.  However, as a homeostatic or compensatory response, these cells have reduced immune potential.   
Members of the Inflammation Research Group also study the mechanisms by which anti-inflammatory cytokines can regulate the production of inflammatory mediators by human macrophages and other cells of the monocyte lineage.  We have previously identified new molecules rapidly produced in human monocytes exposed to the anti-inflammatory cytokine, interleukin-4.   In 2008, the regulatory function of suppressor of cytokine signalling-1 (SOCS-1), a molecule rapidly induced by interleukin-4 and lipopolysaccharide and perhaps representing an important mechanism of control by interleukin-4, has been studied.   Monocytes and macrophages were infected with a SOCS-1-encoding virus and the inflammatory mediator production by these infected cells examined.  Studies to examine the anti-inflammatory properties of SOCS-1 and other similar proteins are continuing in human blood monocytes.

Contact
Email - wayne@ichr.uwa.edu.au
Phone - +61 8 9489 7777
Fax - +61 8 9489 7700

Last updated 10 June 2009