Using CRISPR-Cas9 to understand malaria parasite invasion of hepatocytes

Project Overview

Pathogen ligands for host receptors are often excellent vaccine targets- antibody against them can block invasion of the host cell. Invasion of malaria sporozoites into hepatocytes represents a critical bottleneck in the malaria lifecycle. There is robust proof-of-concept that vaccine-induced antibody can prevent this from occurring, but current vaccine candidates require improvement.

Remarkably, despite this being a critical step in the  lifecycle of an infection which kills >500,000 people every year, there is no clear understanding of the ligand-receptor interactions required for the sporozoite-hepatocyte invasion event.

This project will use a CRISPR-Cas9-based technique to identify the host receptors used by the parasite. Initial work with the technique is already yielding encouraging preliminary data.

Once receptors are identified, you will work to identify the parasite ligands binding to them. The potential of identified parasite ligands as vaccine candidates will be explored using in vitro and humanised mouse models. The Jenner Institute's extensive translational infrastructure will enable the rapid translation of promising candidates towards clinical trials.

Training Opportunities

The project will provide the student with outstanding training opportunities spanning a range of basic scientific skills, experimental & translational medicine.

Laboratory skills will be developed in protein biochemistry, antibody immunology and molecular parasitology. The Jenner Institute is Europe's leading translational vaccinology centre. The student will therefore gain experience in the full breadth of activities involved in the development of new vaccines from pre-clinical concept through to clinical trial, and have the opportunity to participate in developing his or her own ideas along this route.

Theme

Immunology & Infectious Disease and Tropical Medicine & Global Health

Admissions

Project reference number: 906

Funding and admissions information

Supervisors

Name Department Institution Country Email
Dr Alexander (Sandy) D Douglas MRCP Jenner Institute Oxford University, Henry Wellcome Building for Molecular Physiology GBR sandy.douglas@ndm.ox.ac.uk
Professor Adrian VS Hill Jenner Institute Oxford University, Old Road Campus Research Building GBR adrian.hill@ndm.ox.ac.uk

There are no publications listed for this DPhil project.