Schistosomiasis is a global disease that infects more than 207 million people worldwide. Treatment for schistosomiasis primarily relies on the drug, praziquantel, which has been in use for more than 30 years. Although praziquantel is available, over 250,000 people die each year from complications associated with schistosome infection, and there are few new anti-schistosome drugs undergoing active development. The schistosome genome has been sequenced, but a major hurdle for schistosome drug development has been the inability to efficiently manipulate schistosome genetically resulting in our limited understanding of schistosome molecular programs. Our long-term goals are to rationally identify potential drug targets for use against schistosomiasis. We plan to progress toward this goal by defining the regulatory programs required for schistosome development and viability. This process can be facilitated with tools that promote our ability to genetically modif and manipulate schistosome parasites. This study provides an alternative and new method for the transfection of nucleic acid in schistosomes to genetically control schistosome signaling systems through DNA overexpression, protein localization, and the utilization and the development of RNA interference strategies. It will simplify and improve current methods for transfection and will have a major impact on schistosome, and parasitic worm molecular genetics in general.

Public Health Relevance

Schistosomes are parasitic worms that infect more than 207 million humans worldwide and cause debilitating disease. We are exceptionally limited in our ability to genetically manipulate these worms and in our understanding of the basic molecular systems that control it. This project employs a novel new agent to begin to molecularly manipulate the parasitic schistosomes and may facilitate the development of potential new antiparasitic drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI107147-01A1
Application #
8698583
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Joy, Deirdre A
Project Start
2014-04-01
Project End
2016-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
$228,133
Indirect Cost
$78,133
Name
Case Western Reserve University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Liang, Shuang; Varrecchia, Melissa; Ishida, Kenji et al. (2014) Evaluation of schistosome promoter expression for transgenesis and genetic analysis. PLoS One 9:e98302