Manipulating the manipulators: advances in parasitic helminth transgenesis and RNAi

Kalinna, Bernd H.; Brindley, Paul J.

doi:10.1016/j.pt.2007.03.007

Cited by 60 publications

(56 citation statements)

References 51 publications

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“…However, a lack of effective in vitro-culture and genetic methods for parasitic nematodes has hampered the study of the developmental biology of these nematodes [28,[34][35][36]. In contrast, C. elegans provides a powerful surrogate system to shed light on gene function in parasitic nematodes, such as Ancylostoma caninum [37,38], H. contortus [39,40] and S. stercoralis [41,42].…”

Section: Introductionmentioning

confidence: 99%

Exploring the role of two interacting phosphoinositide 3-kinases of Haemonchus contortus

Gasser

Lok

et al. 2014

Parasites & Vectors

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Background: Phosphoinositide 3-kinases (PI3Ks) are relatively conserved and important intracellular lipid kinases involved in signalling and other biological pathways. In the free-living nematode Caenorhabditis elegans, the heterodimeric form of PI3K consists of catalytic (AGE-1) and regulatory (AAP-1) subunits. These subunits are key components of the insulin-like signalling pathway and play roles in the regulation of the entry into and exit from dauer. Although, in parasitic nematodes, similar components are proposed to regulate the transition from free-living or arrested stages to parasitic larvae, nothing is known about PI3Ks in relation to the transition of third-stage larvae (L3s) to parasitism in Haemonchus contortus.

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Section: Introductionmentioning

confidence: 99%

Exploring the role of two interacting phosphoinositide 3-kinases of Haemonchus contortus

Gasser

Lok

et al. 2014

Parasites & Vectors

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“…Transgenesis in the model organism Caenorhabditis elegans was pioneered in the mid 1980s (Fire, 1986;Fire and Waterston, 1989;, and its application to the study of parasitic nematodes began approximately a decade later. As recounted in a recent comprehensive review (Kalinna and Brindley, 2007), initial attempts at transgenesis in parasitic nematodes, which resulted in transient transformation, involved biolistics as a means of gene transfer into relatively large organisms such as adult filariae (Davis, et al, 1999;Jackstadt, et al, 1999;Higazi, et al, 2002) or stages such as the egg of Ascaris suum, which can be obtained in large quantities (Davis, et al, 1999). This approach has been used to study mRNA processing and translation in Ascaris suum (Cohen, et al, 2004;Lall, et al, 2004;Cheng, et al, 2007) and for structural and functional analysis of an HSP70 promoter and of message transplicing in Brugia malayi (Shu, et al, 2003;Higazi and Unnasch, 2004).…”

Section: Introductionmentioning

confidence: 99%

Strongyloides stercoralis: Cell- and tissue-specific transgene expression and co-transformation with vector constructs incorporating a common multifunctional 3′ UTR

Junio

Massey

et al. 2008

Experimental Parasitology

116

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Transgenesis is a valuable methodology for studying gene expression patterns and gene function. It has recently become available for research on some parasitic nematodes, including Strongyloides stercoralis. Previously, we described a vector construct, comprising the promoter and 3′ UTR of the S. stercoralis gene Ss era-1 that gives expression of GFP in intestinal cells of developing F1 progeny. In the present study, we identified three new S. stercoralis promoters, which, in combination with the Ss era-1 3′ UTR, can drive expression of GFP or the red fluorescent protein, mRFPmars, in tissuespecific fashion. These include Ss act-2, which drives expression in body wall muscle cells, Ss gpa-3, which drives expression in amphidial and phasmidial neurons and Ss rps-21, which drives ubiquitous expression in F1 transformants and in the gonads of microinjected P0 female worms. Concomitant microinjection of vectors containing GFP and mRFPmars gave dually transformed F1 progeny, suggesting that these constructs could be used as co-injection markers for other transgenes of interest. We have developed a vector "toolkit" for S. stercoralis including constructs with the Ss era-1 3′ UTR and each of the promoters described above.

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“…New insights into fundamental trematode biology are continually emerging through various genomics, transcriptomics and proteomics projects and due to the application of genetic manipulation technologies such as RNAi and transgenesis. 64,79,80 Integration of these functional analyses will be invaluable in furthering our understanding of SDUDVLWH SDWKRJHQHVLV DQG UHSUHVHQWV D VLJQL¿FDQW VWHS WRZDUG D FRPSUHKHQVLYH XQGHUVWDQGLQJ of host-parasite interplay. Although RNAi and transfection are powerful tools in validating the function of target molecules these technologies are still in their infancy when it comes to their use in trematode biology.…”

Section: Resultsmentioning

confidence: 99%

“…61,62 New insights into the fundamental roles of other trematode cysteine proteases have recently been provided by a number of RNAi and transgenesis studies. 63,64 Skelly et al ZHUH WKH ¿UVW WR VXFFHVVIXOO\ perform knockdown of protease expression in schistosomes. 65 6SHFL¿F VLOHQFLQJ RI 6P&% DFWLYLW\ ZDV GHPRQVWUDWHG E\ LPPXQRÀXRUHVFHQFH 573&5 DQG PRUH LPSRUWDQWO\ SURWHRO\WLF activity.…”

Section: Biological Roles Of Trematode Cathepsin Proteasesmentioning

confidence: 99%

The Phylogeny, Structure and Function of Trematode Cysteine Proteases, with Particular Emphasis on the Fasciola hepatica Cathepsin L Family

Stack

Dalton

Robinson

2011

Advances in Experimental Medicine and Biology

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Helminth parasites (nematodes, flatworms and cestodes) infect over 1 billion of the world's population causing high morbidity and mortality. The large tissue-dwelling worms express papain-like cysteine peptidases, termed cathepsins that play important roles in virulence including host entry, tissue migration and the suppression of host immune responses. Much of our knowledge of helminth cathepsins comes from studies using flatworms or trematode (fluke) parasites. The developmentally-regulated expression of these proteases correlates with the passage of parasites through host tissues and their encounters with different host macromolecules. Recent phylogenetic, biochemical and structural studies indicate that trematode cathepsins exhibit overlapping but distinct substrate specificities due to divergence within the protease active site. Here we provide an overview of the evolution, biochemistry and structure of these important enzymes and highlight how recent advances in proteomics and gene silencing techniques are allowing researchers to probe their biological functions. We focus mainly on members of the cathepsin L gene family of the animal and human pathogen, Fasciola hepatica, because of our deep understanding of their function, biochemistry and structure.

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Manipulating the manipulators: advances in parasitic helminth transgenesis and RNAi

Cited by 60 publications

References 51 publications

Exploring the role of two interacting phosphoinositide 3-kinases of Haemonchus contortus

Exploring the role of two interacting phosphoinositide 3-kinases of Haemonchus contortus

Strongyloides stercoralis: Cell- and tissue-specific transgene expression and co-transformation with vector constructs incorporating a common multifunctional 3′ UTR

The Phylogeny, Structure and Function of Trematode Cysteine Proteases, with Particular Emphasis on the Fasciola hepatica Cathepsin L Family

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