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July 28, 2008 | by  | in Opinion | [ssba]

Identifying the Causes of Asthma

Greg Haslett is doing a BSc (Hons) in Chemistry. He is researching the molecular cause of asthma, attempting to build upon previous research and identify the particular glycoprotein that causes an asthmatic reaction in humans.

New Zealand has the second highest rate of asthma in the world. The macroscopic triggers of asthma are well understood: things like dust mites, mould, pollen and animal fur, etc. But this is only part of the picture, as “there’s something about the dust mite that causes asthma, knowing the trigger on a molecular level would be extremely useful for developing a cure or more effective drugs to treat asthma,” Haslett explains. Current preventative medicine just dumbs down the whole immune system and does not specifically target the asthmatic response.

Asthma is known to be associated with a ‘Th2’ response, which is the activation of a certain kind of white blood cell by the presence of allergens. This is an allergic reaction, and is different from the immune response associated with viruses and bacteria which is called a Th1 response.

Unfortunately, the microscopic or molecular causes of a Th2 response are still unknown, meaning that asthma medication cannot be targeted directly to preventing such a response. It is also not known how the allergen biases the immune system towards a ‘Th2’ response. Haslett’s research aims to discover what the molecular triggers for asthma are which will enable more detailed studies to identify what parts of the immune system are involved in causing the allergic ‘Th2’ response.

Also by identifying the exact molecule that triggers an allergic reaction, biologists can try to identify which enzymes or receptors in the human body the trigger binds to. Biologists can then find other molecules that bind in a similar way to the asthma-causing molecule, blocking the asthma causing molecule from triggering a reaction.

In order to determine the possible molecular trigger for asthma, Haslett’s research supervisors, Dr. Bridget Stocker and Dr. Mattie Timmer, looked at common allergens and found that they all shared a common glycoprotein, a macromolecule with both sugar and protein parts. This glycoprotein is not found in bacteria or viruses which cause a different immune response and is also not found in humans. Haslett’s research aims to build upon their work. He is producing two smaller glycoproteins, both of which contain only part of the glycoprotein identified by his supervisors, which will be tested to see which (if either) will produce the immune response identified with asthma. This is a step towards identifying the ‘minimal structure’ necessary to trigger such a response. One problem faced by scientists attempting to better understand the Th2 immune response is that the glycoproteins tested to date have not been of sufficient purity to identify the exact glycoproteins responsible for the asthmatic immune response. They have been isolated from natural sources, whereas Haslett’s research aims to chemically synthesise pure glycoproteins using known reactions in organic chemistry, which will enable the exact glycoprotein responsible for the response to be identified.

The synthesis of the glycoprotein involved synthesis of the carbohydrate portion in sufficient purity and quantity followed by coupling of the carbohydrate portion to the specific protein (which have been stripped of their native carbohydrates). Finally the testing of the glycoproteins will be conducted at the Malaghan Institute of Medical Research.

Greg Haslett holds a BSc in chemistry from Victoria University. His research builds upon work conducted on a summer internship with the Malaghan Institute of Medical Research, located on campus


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