Schistosomiasis is an important tropical disease caused by schistosome trematodes (a parasitic blood fluke). Those parasites are found in South America and the Caribbean, sub-Saharan Africa, the Middle East, and Southeast Asia. An estimated 200 million people worldwide are infected with schistosomes and 200,000 people die each year. Schistosomiasis is a waterborne disease. Infected freshwater snails release larvae (cercariae) which can infect humans during their water related activities.
Only one drug – praziquantel – is currently available to treat patients but drug resistance starts to emerge. Vaccines have been designed in laboratory but have never conferred decent level of protection to people in the field. Therefore new approaches are needed to identify drug targets, understand drug resistance, predict vaccine efficacy by understanding parasite population diversity and identify potential vaccine candidates.
Inside the Lab
Working with Dr. Tim Anderson, Dr. Chevalier is focusing on genetics of the schistosome parasites, schistosome population genomics, and schistosome drug resistance. He developed an exome capture approach and a sequencing analysis pipeline to analyze data generated from both classical Mendelian genetics (controlled crosses) and parasites sampled in the field. This data helps to identify genes involved in different aspect of the worm biology.
Identification of drug resistance genes and design of new drugs are of major importance for this disease since only one drug – praziquantel – is used as treatment. Another drug – oxamniquine – was used from the 1970s to the early 2000s but was abandoned as a drug treatment due to the rapid emergence and persistence of resistant parasites. But the study of the genetics of these resistant worms allowed identifying the resistance gene and the mechanism of action of this drug. Redesign of oxamniquine is now undergoing with collaborators at UT Health and UTSA in order to increase the drug arsenal against schistosomes. The same approach is currently used to understand praziquantel resistance.
In parallel with drug resistance, Dr. Chevalier is studying the genetics of other traits of this parasite to understand its fundamental biology which may open new avenues for drug targets. Some of these traits are:
- the host specificity between the parasite and its snail vector which will help to identify the parasite genes that allow them to develop within the snail
- the chronobiology that regulates emergence of the cercariae from the snail
The exome capture developed is currently applied to sequence parasites from the field. This is a critical step to understand the genetic diversity of the parasite. Such understanding will help to improve vaccine design by identifying for instance genes under selection because their products are targets of the human immune system. This will also help to have a better understanding of drug resistance: several new alleles involved in oxamniquine resistance were recently identified in Brazil showing clear independent emergence of resistance.
Main Technologies and Methods Used
- Library preparation for high-throughput sequencing (exome capture, RNA-seq)
- PCR / RT-PCR / qPCR
- Sanger sequencing
- Whole genome amplification
- Hamster perfusion / worm and egg collection
- Snail rearing and infection
- Population genomics
- Quantitative trait loci (QTL) analysis
- Transcriptome analysis
- Survival analysis
- Phylogenetic analysis
- Microbiome analysis
- Scripting (bash, R, LaTeX)