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Passing The So What Test

Genetic studies of Eimeria could lead to big breakthroughs in coccidiosis control

Professor Martin Shirley gets frustrated at times. His research into the genetics and genomes of Eimeria could lead to major advances in coccidiosis control. But to anyone outside his field, Shirley’s work seems complicated, futuristic and, well — boring to those involved with poultry production. And talk of it often falls upon deaf ears.

“This is not science fiction,” Shirley says. “I want producers and veterinarians to understand that this research will pass the ‘so what’ test. It has huge potential significance for controlling coccidiosis, which remains one of the economically important diseases in poultry.”

Shirley is director of the Institute for Animal Health (IAH), the largest research institute focused on livestock diseases in the United Kingdom. In the 1980s, he led the team that developed the world’s first attenuated coccidiosis vaccine, which set the stage for what is now known in Europe as the Paracox line.

Today, his focus is nailing down the genetics of E. tenella, the most widespread and problematic of the Eimeria species affecting poultry. Shirley initiated the project and is working jointly with Fiona Tomley, also of IAH, as well as researchers at the Sanger Institute of the UK, the Malaysia Genome Institute, the University of Sao Paolo, Brazil and the Laboratory for Molecular Biology of the UK Medical Research Council.

Benefits for poultry producers

Studying the genetics of the ever-evolving Eimeria, Shirley predicts, will lead to simpler but more effective methods of protecting poultry from coccidiosis. It’s the only way the poultry industry will be able to meet demand, perform up to par and reap better profits, Shirley says.

Shirley and IAH associate Fiona Tomley: ‘This is not science fiction.’

Consider that Eimeria has evolved over tens of thousands of years. It has become adept at subverting the biology of its host — the chicken — to its own advantage, and it’s likely to keep evolving. “We’re trying to untangle that relationship so we can intervene and come up with new control measures as they are needed. It’s a tough challenge,” he says.

Toward that goal, the researchers are ‘mapping’ E. tenella’s genome. Genome is another word for genetic information. In short, Shirley and colleagues are deciphering the parasite’s genetic makeup.

“When we started the work, the genetic information of E. tenella was a bit like having a book that has no chapters, paragraphs, sentences or punctuation and you have to figure out where each strand of words belongs and fits together,” he says.

Until recently, virtually nothing was known about the chromosomes of Eimeria, Shirley says. Chromosomes are the rod-shaped structures in the nucleus, or center, of the cell and they carry the genes which determine the characteristics that an organism inherits from its parents.

E. tenella has a sequence of 14 chromosomes. “When we finish our mapping project, we will have 14 sets of information — one set of information for each chromosome. But keep in mind that these 14 chromosomes comprise millions of pieces of data,” Shirley says.

Unique chromosomes

Shirley (right) reviews a report of the Eimeria genome project with Schering- Plough’s Iain Brown. ‘The industry is embracing vaccines.’

The project to map E. tenella’s genetic structure has already proved interesting because the chromosomes of this species are unique compared to most if not all other organisms that have ever been studied. In fact, they are among the most complex organisms in all of veterinary medicine, he says.

Shirley likens the study of E. tenella chromosomes to discovering the patterns along strings with four different colored beads. “Imagine the 14 chromosomes of E. tenella as 14 strings each containing between 1 million and 14 million of the four differently colored beads,” he says.

Interestingly, a study of the smallest chromosome has revealed that it contains distinct, alternating regions.

Looking from left to right, the beads initially appear as though the colors are distributed randomly, then there are distinct and repeating patterns of color, then seemingly random colors again, then the strong and repeating patterns of color and, finally, seemingly random colors again, Shirley says.

“Our mission is to identify similarities in the patterns of these ‘beads’ and then link them to specific traits that will enhance our understanding of the parasite and the best way to control it,” Shirley says.

E. tenella’s unique arrangement may explain parasitic mysteries such as why Eimeria has become increasingly resistant to drugs. Chromosomes from two Eimeria strains are known to come together during sexual reproduction, he says, but that is all the detail known at present.

Although the genomic mapping of E. tenella is an enormous undertaking, the project is already about 95% complete, Shirley says. Once done, researchers can “data mine,” producing results that will be freely available to anyone in the world who wants to use the information for research or development of commercially useful products.

The IAH researchers want to discover what it is about the Eimeria parasite that causes chickens to develop a protective immune response. They are also looking at a technology known as “transfection,” which enables pieces of DNA to be moved from one parasite into another. The technology might make it possible to develop a “piggyback” vaccine with one parasite that would protect against all species of Eimeria.

Flashback

Anyone who questions whether genetic studies of Eimeria are too futuristic to lead to something practical need only consider the situation years ago when scientists first grew Eimeria parasites in chicken embryos.

At the time, scientists were viewed with skepticism as they tried to discover whether the life cycle of the parasite could be modified, but they found the answer was “yes.” Moreover, the parasites defined by the life cycle changes were attenuated and could be used as live vaccines.” Soon after, the research spawned other, better, approaches to attenuation, which led to the development of the breakthrough coccidiosis vaccine ‘Paracox’, Shirley says.

“When we started collecting precocious Eimeria parasites over 20 years ago, we had no idea they were going to become the sort of global standard for control of coccidiosis with a live attenuated vaccine. No idea at all,” he says. “Today, there are a billion doses a year of the vaccine helping poultry producers control coccidiosis in their flocks.”

Vaccines are the future

Even though the coccidiosis vaccines of today work well, making them requires growing all the different species of Eimeria that cause coccidiosis and then harvesting them from chicken fecal matter to make the vaccines. Birds probably are receiving many more gene products than they need.

In the future, it eventually may be possible and more cost effective to identify exactly which gene products are relevant to immunity, then manufacture — perhaps with genetic engineering — single parasite vaccines that protect against all types of Emeria.

New technology for controlling coccidiosis that arises from the genomic data, Shirley says, is likely to be a vaccine because the continuing use of chemotherapy is under political and other pressures.

“The industry is embracing vaccines and beginning to see that the future of coccidiosis control will depend on vaccines. We’re already facing the prospect in the European Union that drugs may be removed entirely from system because of consumer concerns. We are then left with vaccines and, I believe, as long as there is poultry, there will be a need for Eimeria vaccines. That much is very clear now,” he says.

“For poultry to remain the major meat-producing animal in many parts of the world and remain of importance to the UK, the United States and other countries, there will have to be products that effectively control coccidiosis. And these products will not be developed in 5 minutes by somebody having a ‘eureka’ moment. They will come from sophisticated scientific projects such as genome analyses and genomic mapping,” he says.

For now, Shirley hopes that the poultry industry will take note of E. tenella genetic research, think about its positive implications for the future and meet the researchers with open ears. “Be prepared to support our work, which the industry will need,” he says. “It may not be for the people farming now, but for their sons and daughters and grandsons and granddaughters.”

In turn, researchers have to do their bit, he freely admits, by communicating to the industry in understandable language. “We can be accused of not expressing ourselves in ways that can be properly understood,” he concedes. “I hope the industry is ready to listen and that it challenges us. We both need to meet halfway. There’s work to be done.”