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Griechische Wissenschaftler
Fotis Kafatos (Φώτης Καφάτος) born in Crete/Greece.
PhD 1965 Harvard University , USA. Assistant Professor,
Professor and Chairman, Cellular and Developmental Biology, Harvard University, USA.
Concurrently, Professor of Biology, University of Athens , Greece
and then Professor of Biology, University of Crete , Greece.
and Director, Institute of Molecular Biology and Biotechnology , FORTH,
Heraklion, Crete, Greece.
Director-General and group leader at EMBL since 1993.
Work of the Kafatos Group in the European Molecular Biology Laboratory EMBL:
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Our group is studying the interactions between Plasmodium parasites and the mosquito, Anopheles gambiae. Molecular genetic studies on this socially important organism, a vector responsible for more than two million deaths from malaria each year in Africa, capitalise on recent developments in genome analysis, transgenesis and the comparative study of innate immunity. We aim to trace the immune responses of the mosquito to the parasite, through highly collaborative research, involving close interactions with laboratories in Europe, the USA and Africa (see references).
Genomic characterisation of Anopheles is an important aspect of our studies. Our recent pilot EST project identified a wealth of new A. gambiae genes. We have constructed detailed genetic and physical maps of A. gambiae, localizing genes that are involved in refractoriness to the parasite. The genetic markers are also facilitating the analysis of mosquito population biology and refractoriness in Africa. Sequencing of a 528 kb chromosomes DNA region encompassing one of these genes has permitted a first genomic comparison between A. gambiae and D. melanogaster. Furthermore, we have actively promoted an international collaboration for the whole genome sequencing of A. gambiae.
Previously, we have generated hemocyte-like cell lines which help in analysing mosquito immunity by DNA microarrays and other techniques. Insects and vertebrates share ancient, potent defence mechanisms of innate immunity (distinct from the antibody and T-cell receptor-based adaptive immunity of vertebrates). Our major aim is to dissect these mechanisms in the mosquito, and focus on those pertaining to parasite intrusion. To this effect, we have constructed cDNA microarrays containing over 2,200 Anopheles gambiae genes and used them to analyse global expression profiles of cells and whole mosquitoes in response to microbial challenge, sterile or septic injury and malaria infection. These studies identified novel immune elicitor-specific gene clusters potentially implicated in biochemical and physiological responses to infections. Responses to the parasite extensively overlap with responses to bacterial challenge but not to injury. Furthermore, parasites co-cultured with mosquito cell lines elicit robust responses suggesting specific recognition of the parasite by the mosquito immune surveillance system. Comparison of response profiles of malaria susceptible and refractory mosquitoes has indicated significant differences in immune competence and redox state. Some of the differentially expressed genes are likely to be implicated in the mechanism of parasite killing in the refractory mosquitoes.
Among the molecules transcriptionally up-regulated by bacterial and parasite infections, we have identified a new family of thioester-containing proteins (aTEPs), resembling the complement factors that until recently were considered a hallmark of vertebrates. Using dsRNA knock-down in cell lines, we demonstrated that TEP-I is required for promotion of early phagocytosis, indicating conservation of an ancient complement-like function. We are now extending our analysis to other members of the family. Cell biological studies use advanced light microscopy techniques in conjunction with specific antibodies. The aTEP system is of particular interest, as Plasmodium needs to evade two complement systems - in the mammalian host and in the insect vector.
Transformation techniques provide a crucial tool for genetic and genomic studies. We have participated in developing two genetic transformation methods based on the Minos transposable element in the A. gambiae cell lines and in the germ line of A. stephensi (an important urban vector of malaria in the Indian subcontinent). Refinements underway include development of inducible systems for conditional gene expression and vectors for in vivo RNAi knock-down of genes. With these techniques we can analyse in vivo functions of candidate genes (selected by genetics, cell biology, biochemistry, microarray profiling and bioinformatics) that may be involved in vital physiological pathways of the mosquito, or in mosquito/parasite interactions. Ultimate benefits may be the identification of targets for new environmentally friendly insecticides or targets to block parasite transmission
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RESEARCH & PUBLICATIONS
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PRESS RELEASES
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Publications:
1962-1970 (17)
1971-1975 (33)
1976-1980 (50)
1981-1985 (45)
1986-1990 (47)
1991-1995 (34)
1996-2000 (59)
2001-now (10)
Science Policy Publications (6)
Contact:
Tel.: (+49) 6221-387200
Fax.: (+49)6221-387211
Email: mailto:kafatos@heidelberg.de
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Ancient Greece
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Medieval Greece / Byzantine Empire
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Modern Greece
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