Project description:Trichuris muris is very closely related to the human parasite T. trichiura sharing cross reactive antigens. Moreover, it is a remarkably tractable model system for dissecting immune responses and host parasite relationships and is actively being investigated in a number of laboratories worldwide. T. muris is a naturally occurring nematode parasite of mice which resides in the caecum and colon and has a direct oral faecal life cycle. High-throughput sequencing of Trichuris muris transcriptome for de novo assembly of transcripts. The main objective of this project is to recognize genes expressed in given life stages. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
2013-05-28 | E-ERAD-125 | biostudies-arrayexpress
Project description:Parasite microbiomes and host manipulation
Project description:This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ The human-infective whipworm Trichuris trichiura is estimated to infect up to a billion people and is responsible for considerable morbidity, especially in children of developing countries. The closely related species T. muris is a naturally occurring nematode parasite of mice that serves as a remarkably tractable model system for dissecting immune responses and host-parasite relationships. Such studies are of relevance beyond parasitology as helminths have arguably had a significant impact on the evolution of the mammalian immune system. Both Trichuris species reside in the caecum and colon of the host where they burrow their front end for feeding into the intestinal mucosa, thereby breaching the mucus barrier and allowing access of the microflora directly to the epithelium. The interplay of intestinal helminths, the bacterial microflora and the host immune system is currently a research focus in various laboratories (Bancroft et al 2012). This study will study the transcriptional responses of the intestinal mucosa (caecum) from infected and uninfected mice.
Project description:This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/. We have generated a detailed time-course of RNA-seq from caecum of mice infected with either a high or low dose of Trichuris muris parasites. The data will be used to determine gene expression profiles for each gene in both host and parasite over the course of infection, both for chronic and resolved infections. We will identify genes in host and parasite, which are correlated over the time courses more than expected by chance and use these to generate a list of candidates for host parasite interaction.
Project description:Intracellular pathogens develop elaborate mechanisms to survive within the hostile environments of host cells. Theileria parasites infect bovine leukocytes and cause devastating diseases in cattle in developing countries. Theileria spp. have evolved sophisticated strategies to hijack host leukocytes, inducing proliferative and invasive phenotypes characteristic of cell transformation. Intracellular Theileria parasites secrete proteins into the host cell and recruit host proteins to induce oncogenic signaling for parasite survival. It is unknown how Theileria parasites evade host cell defense mechanisms, such as autophagy, to survive within host cells. Here, we show that Theileria annulata parasites sequester the host eIF5A protein to their surface to escape elimination by autophagic processes. We identified a small-molecule compound that reduces parasite load by inducing autophagic flux in host leukocytes, thereby uncoupling Theileria parasite survival from host cell survival. We took a chemical genetics approach to show that this compound induced host autophagy mechanisms and the formation of autophagic structures via AMPK activation and the release of the host protein eIF5A which is sequestered at the parasite surface. The sequestration of host eIF5A to the parasite surface offers a strategy to escape elimination by autophagic mechanisms. These results show how intracellular pathogens can avoid host defense mechanisms and identify a new anti-Theileria drug that induces autophagy to target parasite removal.
Project description:Toxoplasma gondii is a ubiquitous obligate intracellular parasite that infects the nucleated cells of warm-blooded animals. From within the parasitophorous vacuole in which they reside, Toxoplasma tachyzoites secrete an arsenal of effector proteins that can reprogram host gene expression to facilitate parasite survival and replication. Gaining a better understanding of how host gene expression is altered upon infection is central for understanding parasite strategies for host invasion and for developing new parasite therapies. Here, we applied ribosome profiling coupled with mRNA measurements to concurrently study gene expression in the parasite and in host human foreskin fibroblasts. By examining the parasite transcriptome and translatome, we identified potential upstream open reading frames that may permit the stress-induced preferential translation of parasite mRNAs. We also determined that tachyzoites reduce host death-associated pathways and increase survival, proliferation, and motility in both quiescent and proliferative host cell models of infection. Additionally, proliferative cells alter their gene expression in ways consistent with massive transcriptional rewiring while quiescent cells were best characterized by re-entry into the cell cycle. We also identified a translational control regimen consistent with mTOR activation in quiescent cells, and to a lesser degree in proliferative cells. This study illustrates the utility of the method for dissection of gene expression programs simultaneously in parasite and host.
Project description:We analysed the exosomes secreted by the nematode Trichuris muris. Two replicates of exosomes were analysed using a 5600+ mass spectrometer
Project description:To complete their life cycle, a wide range of parasites must manipulate the behavior of their hosts. This manipulation is a well-known example of the “extended phenotype,” where genes in one organism have phenotypic effects on another organism. Recent studies have explored the parasite genes responsible for such manipulation of host behavior, including the potential molecular mechanisms. However, little is known about how parasites have acquired the genes involved in manipulating phylogenetically distinct hosts. In a fascinating example of the extended phenotype, nematomorph parasites have evolved the ability to induce their terrestrial insect hosts to enter bodies of water, where the parasite then reproduces. Here, we comprehensively analyzed nematomorphs and their mantid hosts, focusing on the transcriptomic changes associated with host manipulations and sequence similarity between host and parasite genes to test molecular mimicry. The nematomorph’s transcriptome changed during host manipulation, whereas no distinct changes were found in mantids. We then discovered numerous possible host-derived genes in nematomorphs, and these genes were frequently up-regulated during host manipulation. Our findings suggest a possible general role of horizontal gene transfer (HGT) in the molecular mechanisms of host manipulation, as well as in the genome evolution of manipulative parasites. The evidence of HGT between multicellular eukaryotes remains scarce but is increasing and, therefore, elucidating its mechanisms will advance our understanding of the enduring influence of HGT on the evolution of the web of life.
Project description:Significant attention has been garnered in proteomic research on Pinus koraiensis infected by Bursaphelenchus xylophilus. This destructive nematode parasite disrupts the cellular structure of the pine, resulting in wilt and death. The key proteins involved in nematode secretion, cell wall degradation, and host defense responses are currently under investigation.