Cel The malaria parasite Plasmodium falciparum, which causes ~600,000 deaths annually, propagates within host erythrocytes. Roughly synchronous egress of blood stage parasites in vivo causes the periodic fevers associated with malaria and is essential for parasite replication. Blocking parasite egress can stop disease progression, so understanding its mechanism is key to identifying new drug targets. Egress of malaria parasites from host erythrocytes involves the rupture of two membranes- the parasitophorous vacuole membrane and the erythrocyte membrane. It is unclear how the parasitophorous vacuole membrane ruptures during egress, and what mechanism is responsible for poration of the erythrocyte membrane. While it has been shown that egress is protease-dependent, the effector molecules that bring about the disruption of both membranes remain unknown. Potential effector molecules include parasite perforin-like proteins (PLPs) and phospholipases. This project aims to test the hypothesis that Plasmodium PLPs and phospholipases are involved in malarial egress. First, we will apply newly developed conditional knockout strategies to establish the role in egress of a candidate perforin-like protein. Second, we aim to devise a novel conditional genetic screen to identify egress related phospholipases in a medium-throughput manner. This work will add to the efforts being made to understand egress and will attempt to develop a much needed forward genetic screen in the malaria parasite. The interdisciplinary approach proposed here combines the experienced researcher (ER)’s skills in genomics and the host laboratory’s expertise in malarial cell biology and conditional knockout technologies. This will equip the ER with the right exposure and new skills to pursue a future independent research career in malaria research. Dziedzina nauki medical and health scienceshealth sciencesinfectious diseasesmalarianatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancenatural sciencesmathematicspure mathematicsmathematical analysisfunctional analysisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Program(-y) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Temat(-y) MSCA-IF-2016 - Individual Fellowships Zaproszenie do składania wniosków H2020-MSCA-IF-2016 Zobacz inne projekty w ramach tego zaproszenia System finansowania MSCA-IF-EF-ST - Standard EF Koordynator THE FRANCIS CRICK INSTITUTE LIMITED Wkład UE netto € 183 454,80 Adres 1 MIDLAND ROAD NW1 1AT London Zjednoczone Królestwo Zobacz na mapie Region London Inner London — West Camden and City of London Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 183 454,80
