This Research Topic will cover research presented at the <a href="https://morgridge.org/research/regenerative-biology/molecular-helminthology-meeting/">2023 Molecular Helminthology conference</a> that will be held in person this year at the Morgridge Institute for Research in Madison, WI from June 26-29, 2023. In addition, we will welcome all other submissions that fall within the scope of the collection. The purpose of the Research Topic is to acquire submissions that present timely advances in molecular helminthology research, including reports from the fundamental biology of helminths to translational research and practical application. We welcome submissions around the five themes that the conference includes this year: a) Immunoparasitology and Diagnostics; b) Drugs and Resistance; c) Developmental Biology; d) Model Organisms; e) New Technologies and Methods; and f) Host-parasite Interactions.

School of Medicine, Washington University in St. Louis

University of Wisconsin-Madison

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Frontiers in Parasitology

Parasitology Omics

Molecular Cellular Parasitology

Immunity and Immune Evasion

Epidemiology and Ecology

Antiparasitic Drugs and Drug Resistance

Parasite Vaccines

Parasite Diagnostics

Molecular Helminthology: From fundamental biology to practical applications

Flatworms depend on stem cells for continued tissue growth and renewal during their life cycles, making these cells valuable drug targets. While neoblasts are extensively characterized in the free-living planarian Schmidtea mediterranea, and similar stem cells have been characterized in the trematode Schistosoma mansoni, their identification and characterization in cestodes is just emerging. Since stem cells are generally affected by irradiation, in this work we used this experimental approach to study the stem cells of the model cestode Mesocestoides corti. We found that gamma irradiation produces a dose-dependent decrease in proliferative cells, requiring higher doses than in other flatworms to completely abolish proliferation. The treatment results in the downregulation of candidate marker genes. Transcriptomic studies reveal that several genes downregulated after irradiation are conserved with other flatworms, and are related to cell cycle, DNA replication and repair functions. Furthermore, proliferative cells were isolated by cell sorting and also characterized transcriptomically. We found that the set of genes characteristic of proliferative cells agrees well with those downregulated during irradiation, and have a significant overlap with those expressed in planarian neoblasts or S. mansoni stem cells. Our study highlights that conserved mechanisms of stem cell biology may be functional in flatworms, suggesting that these could be relevant targets to evaluate in the control of parasitic species.

Flatworms depend on stem cells for continued tissue growth and renewal during their life cycles, making these cells valuable drug targets. While neoblasts are extensively characterized in the free-living planarian Schmidtea mediterranea, and similar stem cells have been characterized in the trematode Schistosoma mansoni, their identification and characterization in cestodes is just emerging. Since stem cells are generally affected by irradiation, in this work we used this experimental approach to study the stem cells of the model cestode Mesocestoides corti. We found that gamma irradiation produces a dose-dependent decrease in proliferative cells, requiring higher doses than in other flatworms to completely abolish proliferation. The treatment results in the downregulation of candidate marker genes. Transcriptomic studies reveal that several genes downregulated after irradiation are conserved with other flatworms, and are related to cell cycle, DNA replication and repair functions. Furthermore, proliferative cells were isolated by cell sorting and also characterized transcriptomically. We found that the set of genes characteristic of proliferative cells agrees well with those downregulated during irradiation, and have a significant overlap with those expressed in planarian neoblasts or S. mansoni stem cells. Our study highlights that conserved mechanisms of stem cell biology may be functional in flatworms, suggesting that these could be relevant targets to evaluate in the control of parasitic species.

Purification and transcriptomic characterization of proliferative cells of Mesocestoides corti selectively affected by irradiation

IntroductionPraziquantel (PZQ), an anthelmintic drug discovered in the 1970s, is still used to treat schistosomiasis and various other infections caused by parasitic flatworms. PZQ causes a triad of phenotypic effects on schistosome worms – rapid depolarization, muscle contraction, and damage throughout the worm tegument. The molecular target mediating these effects has been intimated as a Ca2+-permeable ion channel, but native currents evoked by PZQ have not been reported in any schistosome cell type. The properties of the endogenous PZQ activated conductance therefore remain unknown. </sec>MethodsHere, invasive electrophysiology was used to probe for responses to PZQ from different locales in a living schistosome worm.</sec>Results and discussionNo direct response was seen in tegument-derived vesicles, or from the sub-tegumental muscle layer despite the presence of voltage-operated currents. However, PZQ rapidly triggered a sustained, non-selective cation current in recordings from neuronal tissue, targeting both the anterior ganglion and the main longitudinal nerve cord. The biophysical signature of this PZQ-evoked current resolved at single channel resolution matched that of a transient receptor potential ion channel named TRPMPZQ, recently proposed as the molecular target of PZQ. The endogenous PZQ-evoked current was also inhibited by a validated TRPMPZQ antagonist. PZQ therefore is a neuroactive anthelmintic, causing a sustained depolarization through ion channels with the characteristics of TRPMPZQ.</sec>

Introduction: Praziquantel (PZQ), an anthelmintic drug discovered in the 1970s, is still used to treat schistosomiasis and various other infections caused by parasitic flatworms. PZQ causes a triad of phenotypic effects on schistosome worms – rapid depolarization, muscle contraction, and damage throughout the worm tegument. The molecular target mediating these effects has been intimated as a Ca2+-permeable ion channel, but native currents evoked by PZQ have not been reported in any schistosome cell type. The properties of the endogenous PZQ activated conductance therefore remain unknown. Methods: Here, invasive electrophysiology was used to probe for responses to PZQ from different locales in a living schistosome worm.Results and discussion: No direct response was seen in tegument-derived vesicles, or from the sub-tegumental muscle layer despite the presence of voltage-operated currents. However, PZQ rapidly triggered a sustained, non-selective cation current in recordings from neuronal tissue, targeting both the anterior ganglion and the main longitudinal nerve cord. The biophysical signature of this PZQ-evoked current resolved at single channel resolution matched that of a transient receptor potential ion channel named TRPMPZQ, recently proposed as the molecular target of PZQ. The endogenous PZQ-evoked current was also inhibited by a validated TRPMPZQ antagonist. PZQ therefore is a neuroactive anthelmintic, causing a sustained depolarization through ion channels with the characteristics of TRPMPZQ.