The role of a newly discovered enzyme, indoleamine dioxygenase-2, in health and in disease

Summary

We have discovered the existence of a new enzyme, called indoleamine dioxygenase-2, and where it is located; now we need to find out what it does in the body, which probably relates to the control of blood pressure and male reproductive fertility.

Supervisor(s)

Professor Nicholas Hunt

Research Location

Bosch Institute (Molecular Immunopathology Unit)

Program Type

Masters/PHD

Synopsis

The essential amino acid tryptophan is metabolised in only three ways:

• Incorporated into proteins
• Converted to 5-hydroxytryptamine
• Converted to kynurenine and other metabolites.

It is has been known for 30 years that conversion of tryptophan to kynurenine is accelerated by an enzyme called indoleamine dioxygenase (IDO). Quite recently, Dr Helen Ball in the laboratory discovered that there was a second gene encoding a protein with IDO-like activity. This we now call IDO-2, and the original previously identified gene we call IDO-1. Kynurenine and its metabolites are biologically active in various systems. For example, this pathway has been implicated in the control of blood pressure, regulation of vascular tone and in reproduction. This pathway seems to be abnormally regulated in diseases including Alzheimer disease and cerebral malaria. Furthermore, the enzyme IDO-1 seems to play a very important role in regulating the immune system through its ability to control the proliferation of T lymphocytes and their ability to produce cytokines.The identification of IDO-2 (Ball H et al Gene ePublication 2007) is an important step forward in understanding the complexity of this pathway. We know that the enzyme is rather specifically localised in the body in the tails of spermatozoa and in the kidney tubular epithelium. This project is to investigate those physiological roles and perhaps extend this into disease states like hypertension and diabetes. This project will be within a team effort aimed at identifying the significance of IDO-2 in physiology and disease. The areas of research include: 

• Role in the kidney
• Role in male reproduction
• Role in immunoregulation

Additional Information

Approaches: molecular biology, biochemistry, pathology, physiology. Techniques: cell culture, immunohistochemistry, microscopy, quantitative RT-PCR, epithelial transport studies, sperm motility studies, enzyme kinetics. Other Information: Nick Hunt’s laboratory is in the newly-refurbished Medical Foundation Building. The equipment and other facilities in the building are first class, as are the other research groups located there. His research group contains 3 postdoctoral fellows, 2 PhD students and a part-time technician. The laboratory is well-funded by two National Health and Medical Research Council, one Australian Research Council and one Sir Zelman Cowen Foundation grant in 2009. Scholarhips: Laboratory-funded scholarships may be available for suitably-qualified candidates.

Keywords

Hypertension, infertility, diabetes, indoleamine dioxygenase, tryptophan, kynurenine, sodium transport, spermatozoa, kidney function, Cardiovascular & respiratory diseases, Infertility & developmental problems, Cell biology, Genes in biology & medicine, Human body, Reproduction & development

Opportunity ID

The opportunity ID for this research opportunity is: 114

Other opportunities with Professor Nicholas Hunt

• Pathogenic mechanisms involved in bacterial meningitis
• Mechanism of action of some novel anti-malarial compounds
• Roles of pro-inflammatory and anti-inflammatory cytokines in causing cerebral complications in malaria