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Targeting the blood feeding pathway of the hookworm parasites

Description 
The academic research program within this laboratory is focused on gaining an improved understanding of how helminth parasites and commensal bacteria interact with the immune system both to provide the host with adequate protection against excessive colonization with these organisms and to understand how their presence impacts on organ function, immune homeostasis and heterologous immune responses. We are routinely using 2 rodent models of hookworms, Nippostrongylus brasiliensis and Heligmosomoides polygyrus. Hookworm infections, which cause severe anemia, are considered to be one of the major Neglected Tropical Diseases, affecting 700 million people worldwide. Despite important effort in the eradication of those helminths, current drugs are inefficient at sterilizing the parasite. As a consequence, reinfections are common, thus allowing the infection to persist. The main pathology associated with hookworm infection is anemia and is due to the chronic blood-feeding of the adult parasites throughout many years. The overall goal of the project is to identify and validate new compounds that can be use as drugs for targeting the blood-feeding pathway of helminth parasites. We propose to use the rodent model Nippostrongylus brasiliensis, as this parasite recapitulates many of the characteristics of the major human blood-feeding helminth, the hookworms. It has recently been shown that N. brasiliensis is blood feeding and that targeting blood feeding by vaccination against this stage confers protection. We have recently optimized a drug-screening assay using the parasite in a culture system with purified red blood cells to screen for new drugs affecting the worm viability during blood-feeding. Several interesting compounds have been identified, some specific of the blood-feeding pathway, others capable of targeting the parasite viability through unknown mechanisms. The project will consist in investigating those candidates in more details in other in vitro assays, notably with the adult stage of the parasite, as well as other related nematodes. Candidates than then pass this second screening phase will be further tested in vivo using rodent model of hookworm infections. In parallel, using our already established assay, we will : i) validate candidate drugs from collaborators targeting Haemonchus contortus, a related sheep parasite. Those compounds have been identified using a traditional mobility assay and will now be subjected to our high-throughput viability assay ii) try to determinate the mode of action of the drugs
Essential criteria: 
Minimum entry requirements can be found here: https://www.monash.edu/admissions/entry-requirements/minimum
Keywords 
helminth, drug targeting, blood-feeding, detoxification
School 
Central Clinical SchoolImmunology - Alfred
Available options 
Honours
Time commitment 
Full-time
Physical location 
Alfred Centre, The Alfred Hospital
Co-supervisors 
Dr 
TIffany Bouchery

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