Greg Gibson is a professor of Biology and Director of a new Center for Integrative Genomics at Georgia Tech. His group conducts systems genomics research, building on 15 years of quantitative genetic research in Drosophila, but now with a focus on human genomics. His group is primarily interested in the interaction between genotype and environment and the joint influences of these sources of variation on disease susceptibility and the evolution of disease. While his laboratory combines wet lab assays with statistical genetic and bioinformatics research, integrating transcriptomic studies of host and microbes/pathogens, with metabolomics and clinical profiles.
Plasmodium vivax is the most prevalent malaria parasite in Latin America. It causes endemic exposure to disease in large parts of Colombia, where we have initiated studies of the efficacy of an irradiated sporozoite vaccine. In order to investigate the molecular nature of the immunological response to exposure and vaccination, we have carried out two gene expression profiling studies, one contrasting the malaria response in naïve and semi-immune volunteers, and the other evaluating whether vaccination produces a recognizable immune profile.
In the first study, a total of 16 Colombian malaria naïve (n=7 from Cali) and semi-immune (n=9 from Buenaventura) volunteers were subjected to an experimental P.vivax sporozoite infectious challenge using direct infected Anopheles mosquito bites. We used a Fluidigm nanofluidic qRT-PCR array to profile the expression of 92 genes in whole blood of the 16 individuals across 6 time-points following infection, and followed up with RNASeq analysis of 6 individuals from each location at baseline and first signs of malaria. The results show that there is very little modification of gene expression during pre-patent infection, but strong up-regulation of an interferon-response axis at the peak of parasitemia, and a surprising down-regulation of the inflammatory response at the same time. Approximately 200 genes were differentially expressed between the locations, mostly indicating an accentuated response in the naïve volunteers that correlates with worse malaria symptoms.
In the second study, we performed RNASeq on 22 whole blood samples, taken after immunization but before sporozoite challenge, and after sporozoite challenge at first signs of malaria symptoms in some individuals. We contrasted the responses of 3 control individuals who were not immunized, 3 Duffy-negative individuals who are protected against malaria, and 5 vaccinated individuals, one of whom was fully protected and four of whom showed mild symptoms. Approximately 1000 genes were differentially expressed between the two time-points, resulting in profiles that correspond to some extent with symptomology. Further analyses are expected to shed light on the molecular mechanisms of immune effectiveness.