G-Protein Coupled Receptors as Drug Targets to Treat Schistosomiasis
Abstract
Different species of schistosomes, primarily Schistosoma haematobium, S. mansoni,
and S. japonicum, are responsible for schistosomiasis, which affects over two hundred
million people annually in the undeveloped world. If this disease is left untreated, it can
lead to several major health complications, such as cancer, infertility, and liver fibrosis.
With no available vaccine and the fear of a significant potential public health threat
arising due to the parasite becoming resistant to the only known treatment, praziquantel,
exploring alternative therapies is critical. The goal of my thesis project is to explore new
schistosome drug targets. G-protein coupled receptors (GPCRs) are logical druggable
targets given that they control key aspects of schistosome biology, such as neuromuscular
functions and reproduction. There have been recent updates to the genome assemblies of
each of the three major species of schistosomes. Studies on these GPCRs will require
accurate and updated genome annotation. I reannotated the repertoire of GPCRs present
in the three major schistosome species and identified 17 new S. mansoni GPCRs, 43 new
sequences for S. haematobium, and 61 sequences for S. japonicum (to my knowledge, the
first annotation of S. japonicum GPCRs). I selected several class A neuropeptide
receptors from the S. mansoni genome with high gene expression, which are being
prioritized for this project. These receptors represent a large segment of GPCRs and can
bind one or more neuropeptides. Using gene-specific primers, 11 out of 15 genes with
high expression were cloned and are presently being extended to full length using 5’ / 3’
RACE. With a complete cloned sequence of those genes, the functionality will be tested
to identify possible ligands that engage the receptors and thus provide information on
their pharmacology.
Subject
schistosomiasis
Permanent Link
http://digital.library.wisc.edu/1793/85630Type
Thesis