In order to survive, Plasmodium falciparum needs to transport a large number of proteins into the infected human red blood cell.
Dr Pasternak said knowing exactly how the parasite is able to traffic these proteins would provide researchers with the information needed to stop the parasite ‘dead in its tracks’.
“We are going deeper than any group has gone before to understand the Plasmodium falciparum protein transport process. Our goal is to find a drug or vaccine target that can be used to block the deadly parasite from invading and surviving in humans,” he said.
The researchers will carry out a rigorous analysis of the parasite’s protein export process to build a full picture of what is happening at each crucial stage.
Dr Pasternak said the study was innovative because it combined recent genetic modification techniques with the latest advances in scientific imaging.
“Using the gene editing technique CRISPR, I will modify parasites to allow for the removal of genes in order to see which ones are crucial for the parasite’s survival strategy.
“I’ll also use CRISPR to ‘tag’ the proteins so they become fluorescent and can be easily tracked in the process,” Dr Pasternak said.
Working with Dr Rogers in the Institute’s Centre for Dynamic Imaging, Dr Pasternak will use the revolutionary Lattice Light Sheet microscope to observe live parasites in 3D, over an extended period of time and with unprecedented resolution.
Dr Pasternak said he was “excited to be using tools that had never before been used in malaria studies.”
After shipping frozen parasite samples to London, Dr Pasternak and Professor Baum will use electron cryo-tomography – one of the most advanced tools that currently exists in structural biology – to study the parasites inside human cells.
“We will study the parasites quite literally frozen in time within intact human red blood cells, at every stage of the protein export process.
“I hope the creativity of our approach will help to develop new protocols for malaria research and ultimately solve the structure of the parasite machinery essential for its protein export and survival,” he said.
The Sir Henry Wellcome Postdoctoral Fellowship enables early-career researchers to kick-start high-impact research projects that would not be possible within one organisation alone.
Dr Pasternak said he was especially grateful to the Wellcome Trust for the freedom to pursue his ideas while receiving guidance and support from world-class mentors.
“Such a high-level of independence at an early-career stage is uncommon. I feel very grateful for the opportunity to run with my ambitious project and I hope it will answer big questions of vital importance to global health,” Dr Pasternak said.
Dr Pasternak’s research has also been supported by an EMBO Long-Term Fellowship.
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