• Brugia malayi

Brugia malayi Genomic Studies

Brugia Genome Project

The goal of this project is to assemble and analyze the B. malayi genome estimated to be approximately 95 Mb in size. B. malayi, a parasitic nematode, has six chromosomes, five autosomes and an XY sex-determining pair. Chromosomes are thought to be roughly 10 Mb in size and are difficult to resolve individually. The sequencing strategy utilized a combination of i) whole genome shotgun and ii) end sequencing of inserts from a BAC and fosmid libraries. Although sequenced at very high redundancy (close to 9-fold coverage), the B. malayi whole genome shotgun data have not been assembled into separate chromosomes, because of gaps due to the inherent difficulties in cloning high A/T regions. However, close to 90 Mb of the genome has been assembled into contigs, with 70 Mb built into 8,236 scaffolds. The scaffolds are composed of oriented and ordered fragments interspersed with gaps and span an area of the genome that is estimated to be 80 Mb in size. The state of the assembly has permitted primarily automated curation to be performed, and approximately 11,500 genes have been predicted from this analysis. The functions of many of the genes predicted are unknown as very few have database homologues, and 18% of the 11,500 genes appear to be unique to B. malayi.

Two avenues are presently being pursued:

• Closing and re-assembly of the genome using next-generation pyrosequencing data

  • Collaboration with the group of Steven Salzberg, CBCB, University of Maryland

• High-throughput Analysis of Brugia malayi mRNA 5’ends

Follow this link to view protected content for this project: Brugia malayi/Mapping of 5'ends

Mapping of the interactome between the filaria Brugia malayi and its Wolbachia endosymbiont

The goal of this collaborative project is to understand the ways by which the endosymbiont of B. malayi communicates with its host. We are presently working on mapping the interactome, and on identifying B. malayi nuclear-encoded genes involved in the symbiotic interaction. We are also looking at cis and trans-acting factors that regulate the expression of parasite genes involved in the endosymbiotic relationship.

Collaborators

• Thomas Unnasch, University of South Florida, Global Health

• Sara Lustigman, New York Blood Center, Molecular Parasitology

Collaborative Pages for the Brugia-Wolbachia Interactome Project (protected pages)

Functional characterization of Brugia malayi proteins responsible for host immunomodulation

This project focuses on identifying novel filarial proteins involved in immunomodulation of the human host and characterizing their effect on immune responses. The capacity of the parasite to be tolerated by its host is believed to be facilitated by compounds secreted by the parasite that diminish or redirect the host immune response. We have recently completed the decoding and analysis of the B. malayi genome. Close to 12,000 genes have been identified and at least 30% of these appear to code for novel proteins whose function has not yet been determined. We believe that a number of these ‘orphan’ proteins are responsible for modulating the human immune response. We will use the genomic data to select candidate proteins found to be secreted or excreted by the parasite in its environment and screen their effects on cultured immune cells to outline the immune response profile associated with each worm protein.

Collaborators

• Penny Morel, University of Pittsburgh, Department of Immunology

• Thomas Nutman, National Institutes of Health, Laboratory of Parasitic Diseases/NIAID