Ian van Driel
Research areas
Ian van Driel has two major areas of research:
Cell biology of gastric acid secretion
- The gastric proton pump is responsible for acidifying the contents of the stomach and is expressed by gastric parietal cells.
- Gastric acid secretion has been intensively investigated because of its scientific and medical importance.
Fig 1. A mutant proton pump fails to traffic:
In 'A', the localisation of the normal gastric proton pump is shown in green along with the localisation of a marker for the plasma membrane (yellow). In some cells, the pump is in cytoplasmic vesicles called tubulovesicular elements (TVE) and in other cases it co-localises with the plasma membrane marker.
In 'B', a mutant pump is shown that does not traffic to the TVE
and therefore is always co-localised with the plasma membrane marker
- One of the outstanding features of the gastric proton pump is that the subcellular localisation of the protein is controlled by a regulated trafficking pathway. In quiescent parietal cells that are not secreting acid, the pump resides in an intracellular compartment, the TVE. When parietal cells are activated to secrete acid, the pump moves to the plasma membrane (Fig 2). Our laboratory is investigating the molecular basis and function of this process using unique whole animal and in vitro approaches.
- To date, the vast majority of information concerning the cell biology of membrane and ion transport systems has been gained from analysis of cell lines in vitro. Gastric parietal cells are abundant and relatively homogenous. They have an extensive secretory membrane system. Hence, they are an ideal model for investigation of the cell biology of a “real”, terminally-differentiated cell type.
Fig 2 Parietal cells re-model their secretory membranes:
Quiescent and activated cells contain interconvertible TVE and secretory canalicular
membranes that contain the gastric proton pump. The TVE membranes move to
the plasma membrane and fuse to expand the secretory surface. The membrane
is retrieved by endocytosis when the stimulus to secrete acid is removed.
Autoimmune disease & immunological tolerance
- Autoimmune disease occurs when the immune system is directed against the body's own tissues, resulting in destruction or disruption.
- Afflicting more than 8.5 million people in the US alone, autoimmune diseases are a major public health problem in industrialised nations. Therapies can ameliorate the symptoms of some autoimmune diseases, but for most of them, curative or preventative therapies are unavailable.
- Defining the events and mechanisms that lead to the initiation of autoimmune diseases will lead to an understanding of the processes of immunological tolerance and the development of new predictive, preventative and therapeutic strategies.
- We have concentrated on autoimmune diseases of the stomach - pernicious anaemia and autoimmune gastritis. The prevalence in Western populations of these diseases in people over the age of 60 years is 1.9 per cent. They represent some of the commonest autoimmune diseases and the commonest cause of vitamin B12 deficiency.
Projects
1. Cellular and molecular basis of autoimmune disease
Recent evidence has shown that regulatory or suppressor T lymphocytes play a major role in preventing autoimmunity. Our current aims are to define the relative roles of regulatory T lymphocytes and other mechanisms of tolerance in the pathogenesis and aetiology of autoimmune disease.To further these aims, we have produced an array of knockout and transgenic mice that includes:
- mice deficient in the major gastric autoantigens;
- mice expressing gastric autoantigens ectopically; and
- mice expressing T cell receptors directed to autoantigens.
2. Genetics of autoimmune disease
We are attempting to clone the gastritis susceptibility genes. Our recent analyses have indicated that the gastritis genes may correspond to genes that predispose to other common autoimmune diseases. Hence, this work should make a broad contribution to the understanding of this class of diseases.
Lab personnel
HeadAssociate Professor Ian van DrielResearch staffDr Dorothee Bourges (Research Officer)Dr Desmond Ang ( Research Officer) Nhung Nguyen (Research Assistant) Graduate studentsStacey Allen |
The laboratory
Ian’s laboratory is composed of several postdoctoral scientists, postgraduates and undergraduates who work with a variety of biological systems and problems using a wide range of techniques. These techniques include cell transfection, construction and use of transgenic and knock out mice, many immunological techniques, immunohistochemistry, confocal microscopy, electron microscopy etc.
Ian’s lab has close links with the laboratory of Prof
Paul Gleeson of the Department of Biochemistry & Molecular Biology at the Bio21 Institute. Together, our two groups form a lively and interactive research team.
