Through resources at Harvard University and the Broad Institute, the Sabeti lab is applying next generation, high-throughput sequencing technologies to the creation of tailored sequencing pipelines for some of the world's most deadly viruses and bacteria.
Using both 454 and Illumina technologies, the Sabeti lab is developing novel approaches to full-length genome sequencing for both Lassa fever virus and Ebola virus. With the capacity to generate millions of base pairs of data from less than a teaspoon of blood, we are able to assemble complete viral genomes for identification and genetic analysis of known and unknown viruses.
Working with other collaborators at Tulane University and USAMRIID, the Sabeti lab has obtained a vast repository of valuable clinical samples from patients with viral hemorrhagic fevers. Our hope is to carry out in-depth genomic analysis and diversity studies, elucidating regions of selection and identifying novel strains. The ability to generate full-length sequences will help in creating accurate phylogenies for both Lassa fever and Ebola viruses, as well as refine our ability to predict and identify regions of selection and high mutation within the genomes of these viruses.
In our work studying genetic susceptibility to Lassa, we have established strong collaborations with outstanding partners in Nigeria. Dr. Christian Happi at the University of Ibadan, with whom we have worked for years on malaria, runs a thriving research program at the University of Ibadan.
We are also working closely with and have support from the Provost of the College of Medicine, University of Ibadan, the Chancellor of Ambrose Ali University, and the chief medical director (CMD) of ISTH in Irrua. We have the guidance and participation of arguably the world’s leading expert on Lassa fever, Joe McCormick, former chief of special pathogens at the CDC.
We are working with The Specialist Teaching Hospital in Irrua (ISTH), Nigeria, an ideal location for our study. The hospital, with its 140 physicians and ~16,000 annual patients (80% of which have febrile illness), is located in a rural area in Nigeria where Lassa is endemic with yearly outbreaks.
The hospital has a commitment to research and has collaborated with researchers at the Berhnardt-Nocht Institute (BNI) in Hamburg in one of the best recent epidemiological studies on Lassa. Their 2003-2004 study laid the ground work for our research. It examined 31 febrile patients, 17 healthy contacts, and 12 hospital staff, and got basic rates of infection and exposure for the site.
Cholera is a devastating illnesess caused by the bacillus Vibrio cholerae, which triggers a severe, dehydrating and occasionally fatal diarrhea. We are investigating the genetics of cholera resistance in Bangladesh, where the disease is endemic, to understand how the human immune system responds to cholera infection. Because cholera has a long history in Bangladesh, any person carrying a gene version protecting them from this devastating disease will have had a significant evolutionary advantage. Thus, these genes should show exceptionally strong natural selection signals. By applying powerful new computational techniques for detecting natural selection to genome-wide genotyping data from the Bangladeshi population, we are identifying genes that likely confer cholera resistance. By then integrating these tests with gene transcription profiling and proteomic analysis, we can learn how these genes alter an individual's response to cholera infection. As part of this project, we are also researching the evolutionary history of the Bangladeshis by comparing them to the populations from around the world included in the Human Haplotype Map project.
This project is a collaboration with Dr. Regina LaRocque, an Infectious Disease Specialist at MGH, and ICDDRB an international health research institution and hospital located in Dhaka, Bangladesh that treats tens of thousands of patients every year.
Plasmodium falciparum malaria is a major public health challenge that significantly contributes to global morbidity and mortality. Efforts to control and eliminate malaria combine antimalarial drugs, bed nets and indoor residual spraying, with vaccine development a longer-term goal. Genetic variation in the parasite population threatens to undermine these efforts, as the parasite evolves rapidly to evade host immune systems, drugs and vaccines.
Working with the Broad Institute, the Harvard School of Public Health, and the University of Cheikh Anta Diop, Dakar, Senegal, we have been studying genetic variation in parasite populations to help expand our understanding of basic parasite biology and allow us to track parasites as they evolve in response to interventions.