‘This is the future’ |
IAH’s Martin Shirley is leading the way to mapping the Eimeria genome while
developing even a better understanding of coccidiosis in poultry
For the moment, coccidiosis can wait.
Dr. Martin Shirley has just put in another long day at his lab in Compton, England, where the world-renowned coccidiologist serves as principal scientist for the Institute of Animal Health’s division of molecular biology.
After stopping at his house to squeeze in some chores before taking a long walk through the quiet countryside, he’s ready to unwind at a pub in his hometown of Wantage — a quaint 17th century village some 50 miles northwest of London.
While sipping a frothy pint of his favorite ale, Shirley enthusiastically discusses his latest accomplishment: Converting more than 7,500 songs from his personal CD collection to the MP3 format and cataloging them by artist and genre his home PC, which is wired to a state-of-the-art sound system.
“And I just found a new program that will allow me to transfer all the old stuff I have on vinyl to MP3 while eliminating all the pops and scratches,” he says, clearly embracing the new technology. “So when I’m all done, I’ll have everything from Dylan, Sam & Dave and the Stones to Beethoven, Mozart and Verdi completely catalogued. Every song will be only a mouse click away.”
Cataloging coccidiosis
The following day, when he returns to his lab at IAH, Shirley is all business. He’s still working at his PC labeling and cataloging, only now his focus is the DNA of Eimeria parasites, not the vintage recordings of Led Zeppelin or Stevie Wonder.
“This is the future of coccidiosis management in poultry,” he says confidently.
“In human medicine, if you look at the number of drugs available for controlling diseases, we can effectively hit about 470 biological targets. That sounds like a lot, but not when you consider that our bodies produce something like 30,000 to 40,000 gene products. We still have a long way to go. That’s one of the attractions of the human genome project. Scientists are opening up the whole genome, so potentially, we can find and then tackle every gene that’s linked to a particular disease situation.
“The same is true for Eimeria in poultry,” he adds. “By sequencing Eimeria DNA, or unraveling its genetic code, we can open up the parasite for public display, look at it, dissect it and come up with maybe thousands of potential targets for control in the future.”
‘Complicated’ organism
Shirley notes that Eimeria parasites are “complicated” organisms with perhaps up to 10,000 gene products or, put another way, 10,000 targets for either direct chemotherapeutic or biological control
“At the moment, we have a small portfolio of coccidiosis drugs and vaccines that, while very effective, probably target no more than a half dozen biological targets, perhaps 10 at the most.
“That’s one of the reasons we’re sequencing the DNA of Eimeria,” he continues. “For all the progress we’ve made against coccidiosis in poultry, we really know nothing about the finer points of the biology of Eimeria parasites. For example, almost nothing is known about metabolic pathways, the mechanisms by which the parasite damage the host or of the molecules that stimulate protective immunity [i.e. how and why vaccines such as Coccivac and Paracox are so effective]. All of this information is contained in the genome sequence.”
Shirley says his research team at IAH is concerned primarily with molecular aspects of the Eimeria genome, as well as the genetics of the parasites.
“Without doubt, the most exciting spin-off from our work has been our recent success in securing the funding of a genome sequencing project for Eimeria tenella, which causes cecal coccidiosis in chickens,” he says. “This is a fantastic outcome for the coccidiosis community worldwide, as E. tenella has become the first protozoan of global veterinary importance to be sequenced on a large scale.”
Team of experts
Shirley, IAH colleague Dr. Fiona Tomley and Drs Bart Barrell and Al Ivens from the Sanger Institute, Cambridge, were recently awarded a grant of £750,000 (US$1.2 million from the UK’s Biological and Biotechnological Science Research Council to determine the DNA sequence for the world reference Houghton strain of E. tenella.
“Our previous work has shown that the genome of E. tenella comprises about 60 million base pairs of DNA contained within 14 chromosomes,” says Shirley. “This amount of DNA may give rise to around 8,000 to 10,000 different proteins. But at present, literally only a small handful of these proteins have been identified and only very few of the genes responsible have been characterized.”
When the project is finished, Shirley’s team will have assembled a genetic blueprint for E. tenella and revealed 90% of the parasite’s encoded proteins. All the data generated by the project is being posted on the Internet and available to the public. Shirley says the data will allow current and future coccidiologists to identify new targets for vaccination and chemotherapy.
Eimeria’s ‘life style’
“The data will yield a much greater understanding of how Eimeria parasites go about their life style — for example, how they cause disease, find the correct parts of the gut in which to develop, get in to the host cells, reproduce themselves, cause the host to develop immune responses, and a myriad of other biological features,” Shirley explains.
“In addition, the data will allow the biology of Eimeria parasites to be compared with that of close relatives, such as Plasmodium (the malarial parasites), Cryptosporidium, Neospora and Toxoplasma. If one of these parasites invades in a particular way, for example, you can be sure that Eimeria probably invades the host cell in a similar way. In the research community, there’s a lot of mixing and matching between these different organisms.”
The sequencing initiative under way at the IAH and the Sanger Institute was provided with many letters of support from international scientists and veterinarians working on coccidial parasites and coccidiosis. Shirley says the funding of the work by the BBSRC represents a major push for veterinary science. “To date, the genomes of very few pathogens of purely veterinary importance have been sequenced, and none remotely as big as E. tenella” he says.
But Shirley and his colleagues at IAH and Sanger are not going at this alone. The UK scientists are also collaborating with sequencing efforts by Dr. Arthur Gruber in Sao Paolo, Brazil, and Dr. Wan Kiew Lian at the Universiti Kebangsaan, Malaysia.
“Arthur is doing some great research that dovetails in to the big sequencing initiative and Wan has been awarded a grant from the Malaysian government to derive the complete sequence of chromosomes 1 and 2 (each of 1 million base pairs of DNA),” Shirley says.
“These chromosomes will be sequenced in their entirety to capture all genes and, most interestingly, chromosome 2 is linked to the trait of precocious development that characterizes the attenuated parasites used in Schering-Plough Animal Health’s Paracox, the current attenuated vaccine.”