Professor Julian Rayner FMedSci

The molecular mechanisms of malaria infection

General audience summary:
Malaria remains a devastating, global health concern. In 2017 there were an estimated 219 million cases worldwide with 435,000 deaths – 61 % of which were in children under five (source: World Health Organisation). In my laboratory, we work closely with other scientists in countries where malaria is present as part of the global research effort against malaria. Our focus is on understanding exactly how the malaria-causing Plasmodium parasites are able to infect human red blood cells. In one strand of this research, we are identifying the particular proteins used by the parasites to recognise and target red blood cells. Such proteins could form the basis of potential new vaccines to prevent infection. In the other strand, our research into the genetic makeup of the parasites may reveal potential vulnerabilities for targeting by drugs, and therefore better treatments.

Strategic CIMR theme: Intracellular Infections

Funding: Wellcome Trust, National Institutes of Health (US), European Union

Research Group members: Chris Bowers-Lepts, Carla Briggs, Viola Introini, Emma Jones, Alison Kemp, Prasun Kundu, Balanding Manneh, Allan Muwhezi, Deboki Naskar, Ekta Saini, Eleanor Sylvestor, Viola Introini, Katty Wadda, Kate Webber

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Research

My research seeks to understand the interactions between Plasmodium parasites and human cells, in order to identify and prioritise new drug and vaccine targets. I focus on the stage of the parasite life cycle that infects human red blood cells, as it is this stage that causes all the symptoms and pathology of malaria. We work in three main areas:

Host-parasite interactions. Focusing on the invasion of red blood cells by Plasmodium parasites, we seek to identify new receptor-ligand interactions in order to understand their function during the complex and rapid process of invasion and also explore their potential as vaccine targets. We work closely with Prof. Pietro Cicuta in the Dept of Physics to develop novel video microscopy and biophysics assays to understand invasion at the cellular level, and with Prof. Manoj Duraisingh at the Harvard T.H. Chan School of Public Health to work on Plasmodium vivax, which causes the majority of malaria outside Africa.
Large-scale experimental genetic screens. While at Sanger and in close partnership with Prof. Oliver Billker, now Director of the Laboratory of Molecular Infection Medicine Sweden, we developed scalable genetic technologies and applied them to human, simian and rodent Plasmodium parasites to explore the unannotated half of the Plasmodium genome and prioritise drug targets. We are now combining these with our cellular tools to deepen our understanding of invasion.
Partnership and capacity building. Plasmodium parasites are not model organisms, and all malaria research is rooted in the challenges facing endemic countries. We work closely with partners in Kenya, Ghana, India and Colombia to ensure the tools we develop are accessible to all malaria researchers and support capacity building wherever possible.

Publications

Key publications:

Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis.
Zhang M, Wang C, Otto TD, Oberstaller J, Liao X et al.
Science (New York, N.Y.) 2018;360;6388
PUBMED: 29724925; PMC: 6360947; DOI: 10.1126/science.aap7847

Synergistic malaria vaccine combinations identified by systematic antigen screening.
Bustamante LY, Powell GT, Lin YC, Macklin MD, Cross N et al.
Proceedings of the National Academy of Sciences of the United States of America 2017;114;45;12045-12050
PUBMED: 29078270; PMC: 5692528; DOI: 10.1073/pnas.1702944114

Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes.
Bushell E, Gomes AR, Sanderson T, Anar B, Girling G et al.
Cell 2017;170;2;260-272.e8
PUBMED: 28708996; PMC: 5509546; DOI: 10.1016/j.cell.2017.06.03

A genome-scale vector resource enables high-throughput reverse genetic screening in a malaria parasite.
Gomes AR, Bushell E, Schwach F, Girling G, Anar B et al.
Cell host & microbe 2015;17;3;404-413
PUBMED: 25732065; PMC: 4362957; DOI: 10.1016/j.chom.2015.01.014

Analysis of protein palmitoylation reveals a pervasive role in Plasmodium development and pathogenesis.
Jones ML, Collins MO, Goulding D, Choudhary JS and Rayner JC
Cell host & microbe 2012;12;2;246-58
PUBMED: 22901544; PMC: 3501726; DOI: 10.1016/j.chom.2012.06.005

Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum.
Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M et al.
Nature 2011;480;7378;534-7
PUBMED: 22080952; PMC: 3245779; DOI: 10.1038/nature10606

A scalable pipeline for highly effective genetic modification of a malaria parasite.
Pfander C, Anar B, Schwach F, Otto TD, Brochet M et al.
Nature methods 2011;8;12;1078-82
PUBMED: 22020067; PMC: 3431185; DOI: 10.1038/nmeth.1742

Origin of the human malaria parasite Plasmodium falciparum in gorillas.
Liu W, Li Y, Learn GH, Rudicell RS, Robertson JD et al.
Nature 2010;467;7314;420-5
PUBMED: 20864995; PMC: 2997044; DOI: 10.1038/nature09442

Other Professional Activities

I also have a strong interest in learning and public engagement. I served as Director of Graduate Studies for the Sanger Institute between 2012 and 2014, and am still actively involved in graduate training. I regularly give talks to school and community groups, have helped develop web resources for malaria education, and have collaborated with artists and writers to engage a wide range of audiences in dialogue about science in general, and malaria in particular.

In 2014 I was appointed Director of Wellcome Genome Campus Connecting Science, which enables everyone to explore genomic science and its impact on research, health and society, and I am continuing that work while at CIMR. Connecting Science connects researchers, health professionals and the wider public, creating opportunities and spaces to explore genomic science and its impact on people. We endeavour to inspire new thinking, spark conversation and support learning by drawing on the ground-breaking research taking place on the Wellcome Genome Campus.

Professor of Cell Biology; Director of CIMR; Director of Wellcome Genome Campus Connecting Science