Project description:Giardia duodenalis is a protozoan parasite responsible for gastroenteritis in vertebrates, including humans. The prevalence of G. duodenalis is partly owed to its direct and simple life cycle, as well as the formation of the environmentally resistant and infective cysts. Several proteomic and transcriptomic studies have previously analysed global changes during the encystation process using the well-characterised laboratory isolate and genome strain, WBC6. To expand current comparative analyses, this study presents the first quantitative global study of encystation using pathogenically relevant and alternative assemblage A strains: the human-derived BRIS/82/HEPU/106 and avian-derived BRIS/95/HEPU/2041. We have utilised tandem MS/MS with a label-free quantitative approach to compare cysts and trophozoite life stages between strains for variation, as well as confirm universal encystation markers of Assemblage A.
Project description:Giardia gene expression is being examined using Serial Analysis of Gene Expression (SAGE) to monitor genome-wide levels of messenger RNA (mRNA) expression throughout Giardia's life cycle. Examination of genome-wide gene expression patterns will provide a coherent picture of activation and inactivation of biological pathways. This research will provide a comprehensive understanding of changes in giardial gene expression in response to important host physiological signals and will serve as a valuable model for study of other parasites and complex eukaryotes, such as yeast and animals. It will provide a dynamic framework, in the context of the life cycle, to the annotation of the Giardia genome, including the detection of unpredicted genes via detection of their tags. Keywords: Giardia, SAGE, trophozoites, encystation, excystation, cysts
Project description:The outbreak-causing monkeypox virus of 2022 (2022 MPXV) is classified as a clade IIb strain and phylogenetically distinct from prior endemic MPXV strains (clades I or IIa), suggesting that its virological properties may also differ. Here, we used human keratinocytes and induced pluripotent stem cell-derived colon organoids to examine the efficiency of viral growth in these cells and the MPXV infection-mediated host responses. MPXV replication was much more productive in keratinocytes than in colon organoids. We observed that MPXV infections, regardless of strain, caused cellular dysfunction and mitochondrial damage in keratinocytes. Notably, a significant increase in the expression of hypoxia-related genes was observed specifically in 2022 MPXV-infected keratinocytes. Our comparison of virological features between 2022 MPXV and prior endemic MPXV strains revealed signaling pathways potentially involved with the cellular damages caused by MPXV infections and highlights host vulnerabilities that could be utilized as protective therapeutic strategies against human mpox in the future.
