NEIHPID

Brief Outline of the Project

The majority of metazoan parasites known to invade vertebrate hosts are mainly represented in 3 phyla: Platyhelminthes, Nematoda and Acanthocephala. Many of the parasite members of these phyla are collectively known as helminthes and are causative agents of many debilitating, deforming and killing diseases of man and animals. Among helminth parasites, the lung flukes of the genus Paragonimus have been known as one of the most important zoonotic parasites causing paragonimiasis, also known as haemoptysis in man. It is estimated that more than 20 million people are infected worldwide due to several species (more than 40) of Paragonimus. The best-known species is Paragonimus westermani, whose type locality is probably India and which infects millions of people in Asia causing disease symptoms that mimic tuberculosis. Though the fluke is known to parasitize a wide range of mammalian hosts representing as many as eleven families, the status of its prevalence, host range, pathogenic manifestations and its possible survivors in nature from where the human beings contract infections is not well documented in India. Human diseases caused by pathogenic parasites represent a great, neglected global economic impact and health burden affecting hundreds of millions of children and adults.

Currently there are no vaccine or immunotherapy regimens in circulation for the treatment of any human parasitic infection and pharmaceutical approaches are alarmingly encountering parasitic drug resistance. The recent availability of sequences of several food-borne trematode and helminth parasites in the public domain via GenBank etc. has provided the opportunity to characterize novel antigens and metabolic enzymes essential for the parasite life cycle that might help in predicting novel therapeutic targets. Completed whole genome/ organelle genome sequences of these parasites (Paragonimus, Fasciola and other liver flukes, Fasciolopsis and other gastro-intestinal flukes, Cestode: Taenia and its bladderworm;Nematode: Ascaris, hookworm, filarial worm) whose infections are zoonotic (transferable between man and animals) in nature have opened up avenues for carrying out post-genomic research. Comparisons can be performed within genomes and between genomes. Within genome comparisons will focus on the genome of Paragonimus and scan it from beginning to end, analyzing variations in base composition, k-tuple frequency, gene density, variation in transposable elements, identification of any duplicated regions. Between-genome comparisons will employ closely related organisms (e.g., to identify conserved genes, gene organizations, and control elements) or more distant organisms (to identify genes that are confined to particular clades of a phylogenetic tree). Such data can help trace synteny and gene order and evolutionary trajectories of organisms. Finally the predicted proteome can be functionally annotated and proteomes of organisms can be compared. Post-genome sequence analyses will attempt to confirm, support, and extend the genome annotation via hypothesis-based experimentation into the biological aspects of the parasite life cycle. Delineation of life cycle stages of expression (which can be studied through recent "post-genomic" techniques such as SAGE, etc) followed by probably cellular localization studies, might provide clues as to how complex helminth parasites interact with their hosts, respond to drugs and develop mechanisms of immune evasion or drug resistance. For the helminth parasite, Paragonimus, insights gained by analysis of the annotated genome will probably lead to the discovery of new drug targets based upon novel parasite specific pathways, as well as identification of novel extracellular proteins that may serve as candidates for vaccine targets. Searching gene databases such as KEGG in an attempt to reconstruct metabolic pathways in the organism can make further correlation between the parasite genome and metabolism. The outcome from the integrated research network will be collated into a searchable database and made available on a common portal dedicated to parasite information and analysis.