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Mosquito mission - hunting for the genetic key to wiping out malaria

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-European Molecular Biology Laboratory
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Wednesday 7 December 2005
By Abigail Smith

Controlling malaria through an in-depth understanding of the genetics of mosquitoes is the ultimate goal of Imperial's new Professor of Insect Immunogenomics.

Fotis Kafatos Opens in new window, a pioneer of developmental biology, genomics and insect molecular analysis, joins Imperial from the European Molecular Biology Laboratory (EMBL) where he served as Director General for twelve years.

Moving to Imperial because of the opportunities to work with researchers in a range of complementary disciplines, he and his team are collaborating with other groups at the College to unravel the immune system of Anopheles mosquitoes and understand how they transmit the malaria parasite Plasmodium.

Fotis Kafatos (right), Imperial's new Professor of Insect Immunogenomics, with colleague George Christophides

This is a far from simple process, according to Professor Kafatos, who explains that malaria parasites from the blood of infected mammals complete their development cycle inside the mosquito, maturing and travelling from the gut to the saliva glands.

"The mosquito is not simply a hypodermic needle, taking infected blood from one person and passing it to another when it feeds," he says. "There is a devilishly complex interaction process going on. Understanding how it works is a key to preventing infection from spreading."

Professor Kafatos is joined in his work by his colleague and research collaborator from EMBL Dr George Christophides Opens in new window, now a senior lecturer at Imperial.

At EMBL, they and their co-workers made major strides in understanding this process, discovering numerous genes that act as antagonists, which suppress parasite transmission, or agonists, which protect the parasite against antagonists. They found that when antagonists are inactivated, parasite numbers increase substantially; when agonists are inactivated, parasite numbers drop dramatically. The team is now continuing work based on this discovery at Imperial, and foresees both transgenic and chemical methods being developed to block progression of the parasite in the mosquito. Professor Fotis comments:

"If we can discover safe chemicals that knock out key agonists, we could halt malaria transmission. Curing the mosquito would complement current attempts to develop malaria vaccines or drugs."

In addition to his continuing work on the genomics of mosquitoes, Dr Christophides is already beginning to look at ways to apply the groups work and is collaborating with scientists in Cameroon. He says:

"Our ultimate aim is to bring our lab work to the field to rigorously test whether and how we can interfere with malaria transmission - that's the only way to really find out if we are using the correct approach."

As one of the early leaders of insect gene analysis, Professor Kafatos is excited to be drawing real practical applications from abstract scientific research.

"This mosquito is the most important insect for humanity," he says. "By making it a model for understanding the biology, genomics and immune system of insects, we hope to make a real impact on peoples lives."

About Professor Fotis Kafatos

Fotis Kafatos was born in Crete, Greece, where he received his primary and secondary education. He graduated from Cornell University with a bachelor's degree with high honors and went on to earn masters and doctorate degrees (1965) in biology from Harvard, where he joined the faculty in 1965 and was a full Professor from 1969 to 1994. He served as adjunct Professor of Biology at the University of Athens from 1972 to 1982, Founder and Director of the Institute of Molecular Biology and Biotechnology at the Research Centre of Crete from 1982 to 1993, and since 1982 as adjunct Professor of Biology at the University of Crete. He became Director-General of the European Molecular Biology Laboratory in 1993 which he had led for 12 years before joining Imperial in 2005. He was recently announced as the Chairman of the Scientific Council of the new European Research Council.

Prof Kafatos was one of the early leaders in bringing molecular approaches to the study of development, and helped establish the cDNA cloning technology that has been critical to modern biology. He used this technology in pioneering analyses of the molecular evolution of gene families in insects, including the first demonstration of conserved developmental regulatory elements between distant animals (silkmoth and fruitfly). He was the initiator of the Drosophila genome project and in the last decade has helped change the field of malaria research beyond recognition, by leading the development of molecular approaches to understanding the interactions between the Anopheles mosquito and the Plasmodium parasite. He helped coordinate the Anopheles genome sequencing project and led its subsequent utilisation in functional genomic analyses, focusing on the molecular physiology of infection and mosquito innate immune responses to the parasite.

His scientific achievements and leadership have been recognised by numerous medals, honorary degrees and professorships and memberships in 7 Academies, among which are the National Academy of Sciences, USA, the Royal Society of London (Foreign Member), the French Academy of Sciences (Foreign Member) and the Pontifical Academy of Sciences.

About Dr George Christophides

George Christophides was born in Cyprus and studied in Athens before joining Professor Kafatos at the EMBL and then Imperial College London as an independent investigator.

He has been instrumental in the discovery of mosquito genes that affect parasite development and has developed gene chips and other methods to accelerate such discoveries.