One Wolbachia to rule them all? Testing divergence in the symbiotic biology of clade C and clade D Wolbachia during filarial parasite development
The symbiont, Wolbachia, is a validated drug target in filariasis, although genetic divergences between nematode Wolbachia clades within their filarial hosts may influence aspects of the symbiosis and drug response. The student will therefore investigate comparative biology of a clade D Wolbachia within the veterinary and human zoonotic filarial parasite, Dirofilaria immitis (heartworm) compared with a clade C Wolbachia within the human lymphatic filarial parasite, Brugia malayi.
Wolbachia growth dynamics will be determined by QPCR and imaging analyses at check-points of filarial larval development, utilising novel in vitro and small animal in vivo model systems recently established by the investigators. The anti-Wolbachia and parasitological treatment responses against a panel of registered and novel anti-Wolbachia drugs in development will then be evaluated. Finally, inhibition and rescue type in vitro experiments will be designed to test whether specific metabolic and biosynthetic products provided either by clade C or clade D Wolbachia contribute to their filarial host’s larval development. The project will offer links to multiple industrial partners either researching Wolbachia-based drug targets or developing/repurposing anti-Wolbachia drugs for medical and veterinary use. Further the project may afford field visits to Southern Italy and USA to collect isolates of D. immitis.
Where does the project lie on the Translational Pathway?
T1 (Basic Research)
- Authorship of major research articles detailing the comparative symbiotic requirements of clade C and D Wolbachia and treatment responses
- Proof-of-concept of prophylactic and/or transmission blocking drug targeting clade D Wolbachia
- Molecular parasitology
- Whole animal physiology
- Bioimaging (laser confocal microscopy)
Some prior experience of molecular biology and/or whole animal physiology would be beneficial but not essential