The Clinical-Translational Seminar Series -Dr. George Dimopoulos

"Basically, no one had published on the circadian biology of the mosquito for a very long time. Finally, Dr. Dimopolous published his paper on photic inhibition of blood-feeding in Anapheles gambiae. This paper was crucial to my own research. Dr. Dimopoulos' work and generous advice to me over the years was really valuable to my project and eventual publication with Dr. Duffield."

-- Sam Rund, Ph.D. Cand. in Biology at Notre Dame

(Above: George Dimopoulos and Samuel Rund . Photo: C. Stackowicz, 2012)

October 26, 2012. Dr. George Dimopoulos presented his cutting-edge seminar for CRND to a delighted gathering of faculty and students whose research is focused in infectious diseases and global health. Dr. Dimopoulos's discoveries in vector control at Johns Hopkins Malaria Research Institute are very exciting because of their potential to use the mosquito's own immune system and gut microflora as means of attenuating its transmission of deadly diseases, namely malaria and dengue fever.

Dr. Dimopoulos began with maps. The first illustrated the gradual contraction of malaria endemic areas around the world. Dimopoulos pointed out the key role targeting the vector had played in elimination over 100 years. In the second illustration, Dimopoulos described the emerging growth pattern of dengue fever. According to Dimopoulos, his group works on understanding the processes of infection and immune response to both diseases, in projects that are distinct, but synergistically related. The synergy arises in the broadening of the overall knowledge about the biological processes comprising the mosquito's defense against pathogens, the understanding its genetic structures, and the development of specialized tools that serve a variety of purposes.

Dimopoulos' lab has made significant progress utilizing advanced gene expression analysis methods and technology to analyze the mosquito's functional genomics and characterize pathways, which regulate immune response and resistance to infection. In fact, the Dimopoulos group's project page reports "the first full genome microarrays for Anopheles gambiae, Aedes aegypti, Culex pipiens and Plasmodium berghei" were developed by his lab.

Dimopoulos' discussion of the role of mosquito's own innate immune system, which has evolved to protect it from the malaria parasites it ingests while feeding, summarized a number of experiments leading to the characterization of the "Imd pathway." This pathway plays a crucial role in mediating the mosquito's biological ability to fight off infection. The Dimopoulos Lab's success in describing the progressive immunological responses of the mosquito at the level specific genetic transcriptions is a powerful advance towards gene-based interventions. These interventions will eventually assist the mosquito in resisting infection and consequently reduce it's transmission of the disease to humans. Dimopoulos is careful to underline that the current approach his research aims at is a kind of genetic jumpstart of an existing immune response against the infection based on the mosquito's innate characteristics. The idea, according to Dimopoulos, is to "make the gene turn on earlier" in the infection response and to "not introduce something new."

A key finding of the Dimopoulos group is that specific microflora in the mosquito's gut are critical to its defense against parasitic invasion and the production of sporozoites. It is these sporozoites that infect the salivary glands of the insect and eventually find their way into new hosts when the mosquito feeds.

Visit the Dimopoulos groups project page to read about their advances in vector control research, many of which were described by Dr. Dimopoulos in his brilliantly accessible presentation. Indeed, a number of international students and researchers commented with pleasure on how easy it was to follow Dimopoulos's comprehensive and detailed exposition. In the words of Leonardo DaVinci: “Simplicity is the ultimate sophistication.”

George Dimopoulos, Ph.D., M.B.A. is a Professor in the Department of Molecular Microbiology and Immunology at Johns Hopkins University. He is also the Director of the Parasitology Core Facility and Deputy Director of the Malaria Research Institute, which are part of Hopkins' Bloomberg School of Public Health.

- Building Discovery In Vector Control -

Rund SS, Hou TY, Ward SM, Collins FH, and Duffield GE. (2011). Genome-wide profiling of diel and circadian gene expression in the malaria vector Anopheles gambiae. Proc Natl Acad Sci USA. 2011 Aug9; 108(32):E421-30.

Das, S., and Dimopolous G. (2008). Molecular analysis of photic inhibition of blood-feeding in Anopheles gambiae. BMC Physiology 16; 8(1):23.




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