Project description:Transmission of malaria is dependent on the successful completion of the Plasmodium lifecycle in the Anopheles vector. Major obstacles are encountered in the midgut tissue, where most parasites are killed by the mosquito’s immune system. In the present study, DNA microarray analyses have been used to compare Anopheles gambiae responses to invasion of the midgut epithelium by the ookinete stage of the human pathogen Plasmodium falciparum and the rodent experimental model pathogen P. berghei. Invasion by P. berghei had a more profound impact on the mosquito transcriptome, including a variety of functional gene classes, while P. falciparum elicited a broader immune response at the gene transcript level. Ingestion of human malaria-infected blood lacking invasive ookinetes also induced a variety of immune genes, including several anti-Plasmodium factors. Keywords: Anopheles gambiae, Plasmodium falciparum, ookinete, invasion, innate immunity
Project description:Senescence is a biological phenomenon experienced by all living eukaryote organisms. Genome-wide gene expression associated with aging has been explored in model organisms such as Drosophila melanogaster and Caenorhabditis elegans, but this has not been well understood in African malaria vector, Anopheles gambiae. Gene expression profiling using DNA microarray allows for simultaneous study of changes in mRNA levels for thousands of genes. This study examined genome-wide gene expression during aging process in An. gambiae. The influence of blood feeding on gene expression was also examined. The data can be used to further our understanding of mosquito senescence and identify biomarkers for mosquito age grading.
Project description:Anopheles gambiae mosquitoes are primary human malaria vectors, but we know very little about their mechanisms of transcriptional regulation. We profiled chromatin accessibility by ATAC-seq in laboratory-reared An. gambiae mosquitoes experimentally infected with the human malaria parasite Plasmodium falciparum. By integrating ATAC-seq, RNA-seq and ChIP-seq data we showed a positive correlation between accessibility at promoters and introns, gene expression and active histone marks. By comparing expression and chromatin structure patterns in different tissues, we were able to infer cis-regulatory elements controlling tissue specific gene expression and to predict the in vivo binding sites of relevant transcription factors. The ATAC-seq assay also allowed the precise mapping of active regulatory regions, including novel transcription start sites and enhancers that annotate to mosquito immune-response genes. This study is important not only for advancing our understanding of mechanisms of transcriptional regulation in the mosquito vector of human malaria, but also the information we produced is of great potential for developing new mosquito-control and anti-malaria strategies.
Project description:Proteomic analysis of Anopheles gambiae brain tissue after in-gel trypsin digestion. To gain insights into neurobiology of the Anopheles gambiae mosquito, we carried out a proteomic analysis of its brain using a comprehensive proteomic approach.
Project description:Anopheles gambiae mosquitoes transmit the human malaria parasite Plasmodium falciparum, which causes the majority of fatal malaria cases worldwide. The hematophagous life style defines the mosquito reproductive biology and is exploited by P. falciparum for its own sexual reproduction and transmission. The two main phases of the mosquito reproductive cycle, pre-vitellogenic (PV) and post-blood meal (PBM) shape its capacity to transmit malaria. Transition between these phases is tightly coordinated to ensure homeostasis between mosquito tissues and successful reproduction. One layer of control is provided by microRNAs, well-known regulators of blood meal digestion and egg development in mosquitoes. Here, we report a global overview of tissue-specific miRNA expression during the PV and PBM phases and identify miRNAs regulated during PV to PBM transition. The observed coordinated changes in the expression levels of a set of miRNAs in the energy-storing tissues suggest a role in the regulation of blood meal-induced metabolic changes.
Project description:Background: The mosquito Anopheles gambiae is a major vector of human malaria. Increasing evidence indicates that blood cells (hemocytes) comprise an essential arm of the mosquito innate immune response against both bacteria and malaria parasites. To further characterize the role of hemocytes in mosquito immunity, we undertook the first genome-wide transcriptomic analyses of adult female An. gambiae hemocytes following infection by two species of bacteria and a malaria parasite. Results: We identified 4047 genes expressed in hemocytes, using An. gambiae genome-wide microarrays. While 279 transcripts were significantly enriched in hemocytes relative to whole adult female mosquitoes, 959 transcripts exhibited immune challenge-related regulation. The global transcriptomic responses of hemocytes to challenge with different species of bacteria and/or different stages of malaria parasite infection revealed discrete, minimally overlapping, pathogen-specific signatures of infection-responsive gene expression; 105 of these represented putative immunity-related genes including anti-Plasmodium factors. Of particular interest was the specific co-regulation of various members of the Imd and JNK immune signaling pathways during malaria parasite invasion of the mosquito midgut epithelium. Conclusion: Our genome-wide transcriptomic analysis of adult mosquito hemocytes reveals pathogen-specific signatures of gene regulation and identifies several novel candidate genes for future functional studies.
Project description:Anopheles gambiae mosquitoes play an important role in malaria transmission. In sub-Saharan Africa, the dry season can last several months. The mechanisms for mosquito population to survive through the dry season are poorly understood. One possible mechanism is that adults increase their desiccation tolerance over the dry season. Genetic analyses have shown that inversions 2La, 2Rb, 2Rc, 2Rd and 2Ru are associated with aridity resistance, however little is known about the transcriptional response of genes in response to desiccation. The results of the present study demonstrate that desiccation affects expression of genes associated with several mosquito physiological mechanisms, including those that protect against water loss, but all structural related genes decreased their expression. The identified differentially expressed genes in response to desiccation stress can lay a foundation for better understanding of molecular mechanisms underling dry-season survival of An. gambiae mosquitoes, so it may provide a different option for malaria vector control.
Project description:Senescence is a biological phenomenon experienced by all living eukaryote organisms. Genome-wide gene expression associated with aging has been explored in model organisms such as Drosophila melanogaster and Caenorhabditis elegans, but this has not been well understood in African malaria vector, Anopheles gambiae. Gene expression profiling using DNA microarray allows for simultaneous study of changes in mRNA levels for thousands of genes. This study examined genome-wide gene expression during aging process in An. gambiae. The influence of blood feeding on gene expression was also examined. The data can be used to further our understanding of mosquito senescence and identify biomarkers for mosquito age grading. Transcriptional profiles of Anopheles gambiae female mosquitoes were determined at 1, 4, 10, 19 and 28 days post adult eclosion. Additionally mosquitoes that had access to blood meals were compared to those that were maintained with access to only water and sugar.
Project description:Anopheles gambiae mosquitoes play an important role in malaria transmission. In sub-Saharan Africa, the dry season can last several months. The mechanisms for mosquito population to survive through the dry season are poorly understood. One possible mechanism is that adults increase their desiccation tolerance over the dry season. Genetic analyses have shown that inversions 2La, 2Rb, 2Rc, 2Rd and 2Ru are associated with aridity resistance, however little is known about the transcriptional response of genes in response to desiccation. The results of the present study demonstrate that desiccation affects expression of genes associated with several mosquito physiological mechanisms, including those that protect against water loss, but all structural related genes decreased their expression. The identified differentially expressed genes in response to desiccation stress can lay a foundation for better understanding of molecular mechanisms underling dry-season survival of An. gambiae mosquitoes, so it may provide a different option for malaria vector control. Transcriptional profiles of Anopheles gambiae female mosquitoes were exposed to 70% (standard) or 30% (desiccated) RH without any access to sugar and water at 0hr, 18hr or 36hr.
Project description:We characterize the epigenome of the human malaria vector Anopheles gambiae in midgut cells by mapping the distribution and levels of two post-translational histone modifications, H3K27ac and H3K27me3. These histone profiles were then correlated with levels of gene expression obtained by RNA-seq.