RESEARCH THEMES

Kitsos Louis leads teams that have been involved in the study of malaria with an emphasis in the molecular genetics of Anopheles-Plasmodium interactions for about twenty years. This was based on a foundation of fruit fly molecular genetics that included the membership in the European Drosophila Genome project since the mid-eighties. The long involvement in genomics led to a key role in the Anopheles whole genome-sequencing project. Louis’ team has also been leading in the world in the particular field of mosquito bioinformatics. It developed and hosted AnoBase, the Anopheles database that then evolved, and was fully integrated, in VectorBase.  Moreover, the group has established itself as a vital component in the area of biomedical ontologies.  Non-genomic research of the Louis team focused on the molecular interactions between parasites and the midgut of the mosquito vector during invasion. It expanded its focus to include the microarray-based analysis of insecticide resistance (also on the level of bioinformatics) as well as on the analysis of parasite motility using Plasmodium berghei as a model. All of these activities of the group have been published in a number of publications. The cumulative impact factor of the publications since 2004 is 111.780 with an average of 4.14 for 27 listed by (ISI), of which 9 were co-authored with other members of the NoE network. In July 2007, the total number of citations all of Louis’ publications was 3243 with an average of 38.15 per paper. Louis is an elected member of EMBO and a member of WHO/TDR’s Scientific and Technical Advisory Council (STAC).

The IMBB-FORTH group at Heraklion, Crete, has been focusing its attention on vector-borne diseases with a marked accent on malaria. Over the last 25 years, it has been involved in two main areas, laboratory research of interactions between the arthropod vectors and malaria parasites (using P. berghei as a model) and the bioinformatics of vectors and the diseases they transmit. In the first subject, emphasis was initially put on the molecular events leading to the parasite traversing the midgut epithelium after a blood meal. This focused on the identification and characterization of mosquito proteins that bind Plasmodium and enable its establishment and, thus, the infection of the vector. A variety of methods were used in the lab, prominently cell biological ones (e.g. confocal microscopy) and modern molecular/genomic ones, including proteomics. Functional assays were performed using RNA silencing techniques. This research let to the identification of proteins such as beta-laminin and annexins that were shown to interact with the parasite. Reversing the approach of our research, we have also been using modern analysis tools to study the role of parasite proteins (e.g., among others, perforin 4 and actin II) in the establishment of Plasmodium in the midgut. Finally, recently we initiated research of a, temporally, earlier developmental process of the parasite’s invasion of the mosquito, namely that of gametogenesis, having studied the role of several proteins using both functional assays (knock-outs) and microscopy. As an inheritance of our involvement in mosquito genomics, the second point of interest of our group deals with the bioinformatics of vector-borne diseases. Here, we pioneered the development of a genetic/genomic database for anopheline mosquitoes since the mid-nineties. The original databases, AnoDB and AnoBase, were later (2003) incorporated into VectorBase, an NIAID funded IT tool for vector genomics. The main effort in Crete is the development of bio-ontologies, mostly those that deal with vector-borne diseases. We have produced ontologies for Malaria and Dengue, for the anatomy of mosquitoes and vectors, and for insecticide resistance. We are now attempting the development of an integrated “generic” ontology for vector borne diseases, in other words, one that could be used, for example, to drive integrated decision support systems. In addition to the ontologies, we have developed a database for insecticide resistance and, in collaboration with the group of George Christophides at the Imperial College, London, we also developed a database for insecticide resistance population biology/genetics section for VectorBase. “PopBio” is the first such database tool for this scientific field in the world, and it has been devised such that it can handle data such as population studies, of insecticide resistance, and similar sets of information that could be used in vector control. Needless to that small side projects, some of which lie outside the main areas of interest of our group are also being carried out, such as ontologies for agricultural pests and microRNAs.

SELECTED PUBLICATIONS

• David, J.P., Strode, C., Vontas, J., Nikou, D., Vaughan, A., Pignatelli, P.M., Louis, C., Hemingway, J. and Ranson, H.(2005) The Anopheles gambiae Detoxification Chip: a new highly specific microarray to study metabolic based insecticide resistance in malaria vectors. Proc. Natl. Acad. Sci. USA 102, 4080-4084. (PMID: 15753317)
• Siden-Kiamos, I., Ecker, A., Nybäck, S., Louis, C., Sinden, R.E. and Billker, O. (2006) Plasmodium berghei Calcium Dependent Protein Kinase 3 is required for ookinete gliding motility and mosquito midgut invasion. Mol. Microbiol., 60, 1355-1363 (PMID: 16796674)
• Lawson, D., Arensburger, P., Atkinson, P., Besansky, N.J., Bruggner, R.V., Butler, R., Campbell, K.S., Christophides, G.K., Dialynas, E., Hammond, M., Hill, C.A., Konopinski, N., Lobo, N.F., MacCallum, R.M., Madey, G., Megy, K., Meyer, J., Redmond, S., Severson, D.W., Stinson, E.O., Topalis, P., Birney, E., Gelbart, W.M., Kafatos, F.C., Louis, C. and Collins, F.H. (2009) VectorBase: a data resource for invertebrate vector genomics. (2009) VectorBase: A home for invertebrate vectors of human pathogens. Nucl. Acids Res, 3, D583-7. (PMID:19028744)
• Topalis, P., Lawson, D., Collins, F.H. and Louis, C. (2008) How can ontologies help vector biology? Trends Parasitol. 24, 249-252. (PMID: 18440275)
• Dialynas, E., Topalis, P., Vontas, J. and Louis, C. (2009) MIRO and IRbase: IT tools for the epidemiological monitoring of insecticide resistance in mosquito disease vectors. PLoS Negl. Trop. Dis. 3(6): e465. doi:10.1371/journal.pntd.0000465 (PMID: 19547750)