Eureka award winner finds chink in parasites' armour

Molecular parasitologist Dr Sabina Belli finds relief from the stresses of a busy research career in kayaking and white-water rafting.

Belli feels an obligation to warn fellow aquatic thrill seekers about the tiny water- and blood-borne parasites they can encounter while adventuring in locales like Nepal and India. They’re not always impressed.

But Belli’s peers are certainly impressed by the quality of her research. Last night, the Sydney University of Technology (UTS) molecular parasitologist was awarded the University of NSW Eureka Prize for Scientific Research in a ceremony at the Hordern Pavilion in Sydney.

The former Monash University PhD, who works at UTS’ new Institute for the Biotechnology of Infectious Diseases, described winning the prestigious award as “absolutely fantastic”.

“I can’t believe something like this has happened to me,” she said. In addition to boosting her own profile as a researcher,

Belli is delighted because she believes the award will also bring recognition to the new institute, and it recognises the importance of veterinary research, which tends to be overshadowed by the almost daily miracles of medical research.

Belli has found a chink in the formidable armour of the word’s most abundant livestock parasite, Eimeria maxima, the agent of the debilitating disease coccidiosis on poultry farms around the world.

Dr Belli’s achievement has implications beyond its potential to help veterinary vaccine and drug-developers to develop new ways to prevent coccidiosis.

Belli chose Eimeria as a model for the diverse microscopic hordes of the phylum Apicomplexa, a veritable rogue’s gallery of the world’s most troublesome parasites of vertebrates, including:

• Plasmodium, the deadly, blood-borne agent of human malaria, which kills up to 2 million children annually.
• Cryptosporodium, a waterborne agent of diarrhoea in humans and animals
• Toxoplasma, the cause of toxoplasmosis, a ‘flu-like infection that kills many AIDS patients and individuals with compromised immune systems, as well causing foetal brain damage in pregnancy, and
• Neospora, which causes abortion in cattle.

The Apicomplexa are obligate parasites, with complex life cycles that alternate between sexual and asexual stages.

Most species, like Eimeria and Cryotosporidoum, form tough-coated resting spores called oocytes, that resist desiccation and biochemical breakdown while they lurk in the environment, waiting to infect new hosts.

For 80 years parasitologists have been trying to determine how the oocyst wall forms, and, more recently, to identify the genes involved in its synthesis.

Dr Belli has succeeded where her predecessors failed. She has applied sophisticated immunological and recombinant DNA (gene technology) techniques to crack the evolutionary secret that makes Apicomplexa such successful parasites.

In their active state, Apicomplexa are delicate, soft-bodied organisms that cannot survive outside the protected environment of the host’s body. But at some stage in their complex life cycles, most Apicomplexa transform into tough cysts that can survive the harsh, often desiccating conditions of the external environment.

Because it is very difficult to grow Eimeria and other apicomplexan parasites in vitro, they have defied efforts to elucidate how they transform into cysts, and to determine what the tough cyst wall is made of.

Dr Belli’s Eureka Prize assessors all praised the ingenious and rigorous way in which she addressed and answered these questions in her ground-breaking research into Eimeria.

She has discovered that during its macrogamete phase – the sexual stage preceding cyst formation - Eimeria synthesises large amounts of two proteins, gam56 and gam82. These proteins, the precursor materials for the cyst’s cell wall, accumulate in intracellular vesicles called wall-forming bodies.

Dr Belli cloned the genes for both proteins, enabling her to synthesise them to study the biochemical processes by which they form the cyst wall. She has shown the proteins are cleaved by an enzyme to yield protein fragments rich in the amino acid tyrosine.

The tyrosine residues are then oxidised, linked and the fragments harden to form a molecular chain-mail armour that protects the dormant parasite against desiccation and biochemical attack while it waits in the environment, ready to infect new hosts.

By confirming that the Eimeria macrogamete is the only life-cycle phase that makes the precursor proteins for the cyst wall, Dr Belli has provided important clues for the developers of new vaccines and drugs – not just for Eimeria, but potentially for all other Apicomplexa parasites, including the deadliest of the four species of parasites that cause malaria in humans, Plasmodium falciparum.