African sleeping sickness in humans is a potentially deadly disease caused by trypanosomes (Trypanosoma brucei spp.). Central to inhibiting the spread of this rapidly re-emerging disease is control of the arthropod vector, the tsetse fly (genus Glossina). Tsetse harbors a commensal endosymbiotic microorganism (Sodalis glossinidius) that lives in the midgut in close proximity to the trypanosomes. The goal of this research is to exploit this symbiotic flora for the purpose of decreasing tsetse's capacity to transmit trypanosomes. To accomplish this goal, I plan to improve upon an existing extra-chromosomal plasmid-based transformation procedure by using homologous recombination to incorporate 'effector molecule' genes into Sodalis' chromosome. 2 candidate molecules, with demonstrated trypanolytic activity, are available for this purpose: tsetse attacin and vertebrate BMAP-27. Recombinant Sodalis will be reintroduced to tsetse. These 'paratransgenic' flies and their offspring will then be monitored for changes in fitness, stability of recombinant protein expression and trypanosome vectorial capacity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI062680-03
Application #
7244283
Study Section
Special Emphasis Panel (ZRG1-F13 (20))
Program Officer
Costero, Adriana
Project Start
2005-06-09
Project End
2008-06-08
Budget Start
2007-06-09
Budget End
2008-06-08
Support Year
3
Fiscal Year
2007
Total Cost
$52,048
Indirect Cost
Name
Yale University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Aksoy, Serap; Weiss, Brian L; Attardo, Geoff M (2014) Trypanosome Transmission Dynamics in Tsetse. Curr Opin Insect Sci 3:43-49
Weiss, Brian L; Wu, Yineng; Schwank, Jonathon J et al. (2008) An insect symbiosis is influenced by bacterium-specific polymorphisms in outer-membrane protein A. Proc Natl Acad Sci U S A 105:15088-93
Weiss, Brian L; Mouchotte, Rosa; Rio, Rita V M et al. (2006) Interspecific transfer of bacterial endosymbionts between tsetse fly species: infection establishment and effect on host fitness. Appl Environ Microbiol 72:7013-21