Crystal elegance reveals viral solutions

Dr Fasseli Coulibaly has found beauty beneath the surface of the most brutal human diseases. His enchantment with the elegance of virus architecture has led to a pioneering study of crystallised insect virus proteins, which could provide the first vaccines to protect against complex diseases such as HIV.

Fasseli is using robust protein microcrystals, which originally occur in insect viruses, to develop a novel platform of viral vaccine delivery. The microcrystals could improve antigen delivery because they can carry the kind of complex vaccines required to fight pathogens such as HIV.
Fasseli says the microcrystals are also very stable, meaning they are well suited to developing countries where refrigeration is not guaranteed.

The research, funded by the Bill and Melinda Gates Foundation, is being undertaken in partnership with a Burnet Institute team led by Associate Professor Rosemary Ffrench.

It is based on Fasseli's 2007 breakthrough made at the University of Auckland with Peter Metcalf and Japanese collaborator Hajime Mori, which has been documented in Nature. He used X-ray crystallography to identify the structure of miniscule insect virus proteins for the first time. X-ray crystallography uses synchrotron light to analyse protein crystals in three dimensions.

X-ray crystallography is also a fundamental part of his research to better understand smallpox and hepatitis C viruses. The Australian synchrotron is essential to this work. Its intense X-ray light beams are already being used to reveal how smallpox virus protein crystals are assembled. This could potentially lead to smallpox antivirals.

'It is like switching on a light in a dark room,' Fasseli says. 'If you manage to crack the structure you can understand the virus strategies in their most intimate detail, which can ultimately lead to the development of new drugs.'

Unlike synthetically produced protein crystals, which can take years to develop, Fasseli's insect protein virus can spontaneously crystallise. This increases the protein's stability, making it ideal for use in developing countries - to which Fasseli has a personal connection.

'My father's family is from Mali in West Africa, so it is satisfying to do something that could have an impact there,' the French expatriate says.

Fasseli and his team are also developing crystals for a hepatitis C project with Dr Heidi Drummer's Burnet Institute laboratory, aimed at understanding how the virus invades host cells. This has implications for the design of new vaccines and antivirals.

Besides the potential health benefits that flow from his work, Fasseli says he is drawn to the simple elegance of this microscopic world.

'Viruses are very inventive at finding ways of going around cell defences, so this elegance in the viral processes is what I like,' he says. 'And as for the structural biology, what I really love is what we see. We reveal molecular structures for the first time, but the crystals themselves are beautiful. I love seeing them.'