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 (carbohydrates) 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 carbohydrates for testing in Th2 immune response assays.
We hope that these studies will provide the first detailed insight into the relationship between carbohydrate 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: Small molecules in cancer therapy
A) Cancer Immunotherapy: 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. We are currently synthesising a variety of novel glycolipids to enhance anti-tumour immunity.
B) Natural Products to Target Cancer: A number of compounds isolated from natural sources are known to have anti-cancer potential. Our efforts in this area focus on the synthesis of natural product derivatives (quinones), which have been shown to have an interesting mode of action in the killing of tumour cells. On route to synthesising our final quinone targets, we have also identified many other promising lead compounds.
Project Three: Synthesis of designer drugs against Mycobacterium 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.
These compounds are being synthesised using a novel approach that we developed in 2008, which gives high yields while having the added advantage of being better for the environment.
Collaborators
Industrial Research Ltd, New Zealand
New Zealand Pharmaceuticals
Victoria University of Wellington, New Zealand
Funding
Cancer Society of New Zealand
Health Research Council of NZ
New Zealand Lottery Health Research
Tertiary Education Commission
Victoria University Research Grant
Wellington Medical Research Foundation
