Evolutionary genetics of tsetse and its symbionts

Summary

Principal Investigator: S Aksoy
Affiliation: Yale University
Country: USA
Abstract: Human African trypanosomiasis (HAT) kills thousands of people each year in sub-Saharan Africa. The disease is caused by African trypanosomes transmitted by the tsetse fly. HAT transmission is complex; it requires mammalian and invertebrate hosts and involves domestic and wild reservoirs. No mammalian vaccines exist and therapeutic drugs have serious side effects with increasing resistance seen in patients. In contrast, reduction of tsetse populations is highly efficacious for disease control. However, the implementation of the tsetse control programs, which rely on traps and targets, have been difficult to sustain because they are not practical and require extensive community participation. A paratransgenic strategy has been developed which exploits the unique biology of tsetse and its maternally inherited bacterial symbionts. In this strategy, tsetse's mutualist symbiont Sodalis is harnessed to express trypanosome inhibitory molecules in tsetse's midgut to impair trypanosome transmission. Transgenic Sodalis bacterium conferring refractoriness may be driven into natural tsetse populations by cytoplasmic incompatibility phenomenon mediated by tsetse's symbiont, Wolbachia. We propose to investigate the biogeography of the human disease vector species, Glossina fuscipes fuscipes, its Trypanosoma parasite(s), and its Wolbachia and Sodalis symbionts. Using a combination of laboratory and field experiments, we will investigate the potential for a Wolbachia mediated gene-drive mechanism to aid in the application of paratransgenic flies. In addition, we will elucidate the basic genetic structure of this human disease vector population, for which no information exists. This information is necessary for the efficacious implementation and monitoring of either the traditional or novel control strategies. Knowledge obtained on symbiont biology, maternal linkage of tsetse's multiple symbionts, Wolbachia infection phenotype, potential strength of Wolbachia mediated drive, population genetics and epidemiological dynamics will provide the parameters needed to develop a mathematically based model framework. This model will allow us to test the predictive nature of the empirical data, design the optimal strategies for population control, and predict feasibility and robustness for the success of the replacement strategy. This interdisciplinary application will combine epidemiology, population genetics and modeling with model parameterization and verification from laboratory and field research.
Funding Period: 2008-01-15 - 2012-12-31
more information: NIH RePORT

Top Publications

  1. pmc Prevention of nosocomial transmission of extensively drug-resistant tuberculosis in rural South African district hospitals: an epidemiological modelling study
    Sanjay Basu
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA
    Lancet 370:1500-7. 2007
  2. pmc Infections with immunogenic trypanosomes reduce tsetse reproductive fitness: potential impact of different parasite strains on vector population structure
    Changyun Hu
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, USA
    PLoS Negl Trop Dis 2:e192. 2008
  3. pmc Characterization of the antimicrobial peptide attacin loci from Glossina morsitans
    J Wang
    Yale University School of Medicine, Department of Epidemiology and Public Health, 60 College Street, New Haven, CT 06510, USA
    Insect Mol Biol 17:293-302. 2008
  4. pmc Multiple-strain infections of Trypanosoma brucei across Africa
    Oliver Balmer
    Department of Ecology and Evolutionary Biology, Yale University, 165 Prospect Street, New Haven, CT 06511, USA
    Acta Trop 107:275-9. 2008

Scientific Experts

  • Sanjay Basu
  • Oliver Balmer
  • J Wang
  • Changyun Hu
  • C Hu
  • M Hattori
  • Amy F Savage
  • Rita V M Rio
  • Alison P Galvani
  • Terry W Pearson
  • A Toyoda
  • Serap Aksoy
  • Y Wu
  • M Berriman
  • A Stuart
  • Jan Medlock
  • S Aksoy
  • Nurper Guz
  • Lee R Haines
  • Geoffrey M Attardo
  • C Amemiya
  • Dana Nayduch

Detail Information

Publications4

  1. pmc Prevention of nosocomial transmission of extensively drug-resistant tuberculosis in rural South African district hospitals: an epidemiological modelling study
    Sanjay Basu
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA
    Lancet 370:1500-7. 2007
    ..We modelled the plausible effect of rapidly available infection control strategies on the overall course of the XDR tuberculosis epidemic in a rural area of South Africa...
  2. pmc Infections with immunogenic trypanosomes reduce tsetse reproductive fitness: potential impact of different parasite strains on vector population structure
    Changyun Hu
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, USA
    PLoS Negl Trop Dis 2:e192. 2008
    ..Potential repercussions for vector population growth, parasite-host coevolution, and disease prevalence are discussed...
  3. pmc Characterization of the antimicrobial peptide attacin loci from Glossina morsitans
    J Wang
    Yale University School of Medicine, Department of Epidemiology and Public Health, 60 College Street, New Haven, CT 06510, USA
    Insect Mol Biol 17:293-302. 2008
    ..Transcription of AttD is significantly less relative to the other two genes, and is preferentially induced in the fat body of parasitized flies. These results indicate that the different attacin genes may be differentially regulated...
  4. pmc Multiple-strain infections of Trypanosoma brucei across Africa
    Oliver Balmer
    Department of Ecology and Evolutionary Biology, Yale University, 165 Prospect Street, New Haven, CT 06511, USA
    Acta Trop 107:275-9. 2008
    ..Together with previous results, these findings strongly suggest that multiple-strain infections are common for this parasite and that their consequences for epidemiology and parasite evolution should be investigated in detail...