Immunoglycomics Current Research
Project One: A sweet approach to asthma
While much is known about the causes of asthma, few studies have looked at the molecular structures of the allergens that trigger the disease and the role they play in influencing Th2 immune responses.
Upon close examination of the structural features of allergens such as pollen, food, and worms, we observed that particular structures (N-glycans) were conserved. Interestingly, antigens derived from bacteria and viruses neither possess these carbohydrate structures nor stimulate allergic immune responses, leading us to hypothesise that these unique structural motifs might be responsible for biasing the immune response towards Th2.
To investigate this hypothesis we are in the process of synthesising a library of N-glycans for testing in Th2 immune response assays.
We hope that these studies will provide the first detailed insight into the relationship between N-glycan structure and Th2 bias and will lead to the identification of specific Th2 targets that will aid in the diagnosis and treatment of asthma and allergy.
Project Two: Improving cancer immunotherapy with designed glycolipids
Immunotherapy holds promise as a new treatment for cancer. In a typical cancer immunotherapy programme, tumour cells are extracted from a patient and used to prepare a vaccine designed to stimulate an anti-tumour immune response. Though tumour regression has been observed in a number of patients using this approach, the immune response is not robust.
The addition of certain glycolipids however, acting as adjuvants, boosts the immune response in favour of enhanced anti-tumour activity. While the tumour-derived peptide effectively acts as the "ignition" and turns the immune response "on", the glycolipid acts as the "throttle" and controls the intensity of the immune response.
Cells that react to glycolipid molecules, called iNKT cells, have been shown to have significant regulatory influence over the anti-tumour immune responses. We propose that cancer immunotherapy can be improved by selecting appropriate glycolipids to "fine tune" iNKT cell activity in vivo. We will synthesise a variety of novel glycolipids and, by focusing on the influence that specific glycolipids have on the immune bias, aim to promote iNKT cell activities that favour anti-tumour immunity.
Project Three: Synthesis of designer drugs against the bacterium that causes Tuberculosis
Tuberculosis (TB) kills more people than any other infectious disease. A staggering one-third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of TB. Though once considered to be a third-world disease, over recent years there has been an increase of tuberculosis in the so-called ‘developed countries'. In New Zealand a person contracts tuberculosis daily. The current vaccine for tuberculosis, BCG (Bacillus Camette Guerin), is the least effective vaccine in use today with reports of its efficacy ranging from 0 to 80%. Additionally, drug resistant strains of TB have emerged.
In view of the problems associated with current TB treatments, we aim to synthesise a novel class of drugs that target the sugar-making enzymes involved in maintaining the structural integrity of the mycobacterial cell membrane. Arabinose sugars are crucial to the survival of mycobacteria but are not found in humans, so a drug designed against their synthetic pathway is likely to kill the bacteria while having minimal side-effects on the patients being treated.
