Abstract
Leishmania parasites are transmitted via the bite of infected female sand flies. Inside this vector, parasites have to overcome different hurdles before they can differentiate into their metacyclic, infective form, during a process which is called metacyclogenesis. This PhD project will focus on the identification of Leishmania infantum genes that can influence the development and metacyclogenesis of parasites in the vector and hereby impact successful transmission from sand fly to vertebrate host. As both up- and downregulation of certain genes may result in enhanced transmission, two different methodologies will be applied to identify potential transmission-related genes, both in collaboration with prof. dr. Ouellette (Quebec, Canada). On the one hand, repeated infection of sand flies with an already established Leishmania COSMID library will allow for selection of more transmissible parasites that harbor those specific COSMIDs containing genes providing a benefit in the vector. Genes responsible for these observed gain-of-functions in the sand fly will be unveiled using COSMID sequencing. On the other hand, loss-of-function will be explored in parallel using a similar approach for a recently developed Leishmania CRISPR-Cas9 library. Ultimately, the identification of genes involved in transmission not only will provide useful insights on the transmission process, but it might also open doors for the development of novel transmission-blocking strategies in the future.
Researcher(s)
Research team(s)
Project type(s)