On World Malaria Day 2019 - celebrating malaria research at the University of Edinburgh
Here we highlight some of the groundbreaking researchers based in the School of Biological Sciences at the University of Edinburgh who are tackling malaria.
Malaria remains a huge burden on many people living in the developing world – each year over 0.5 million people die from the disease and another 200 million are infected. The Plasmodium parasites which cause the disease are carried by mosquitoes.
And with climate change bringing rising temperatures worldwide, mosquitoes and the diseases they carry, are continuing to threaten us all.
Meet the researchers
Dr David Cavanagh - Developing malaria vaccines
Our research interests centre on the immunobiology of the human malaria parasite, Plasmodium falciparum. We examine the development of antibody responses to the malaria parasite in naturally exposed individuals, linking these to protection against clinical malaria episodes. The main thrust of our research at present is the development of malaria vaccines.
We have two main vaccine targets:
Merozoite surface protein 3.3. We have shown that MSP3.3 is exported to the cytoplasm during parasite development in the RBC, and is also found on the surface of merozoites after RBC lysis. Antibodies raised by immunisation to MSP3.3 have potent anti-parasite effects, and (intriguingly) retard parasite development inside the infected red blood cell. We are currently characterising the location and functions of MSP3.3 to better understand its role in parasite development.
Merozoite surface protein 1. We have identified a novel target for malaria vaccine development, namely the Block 2 region of merozoite surface protein 1 (MSP-1 BL2). We showed that MSP-1 BL2 is the target of naturally acquired antibodies associated with protection from clinical malaria symptoms in African children. We protected Aotus lemurinus monkeys against experimental virulent malaria infection, by immunisation with MSP-1 BL2. We have developed and pre-clinically tested vaccine constructs based on MSP-1 BL2 including hybrid measles-malaria virus vaccines and more conventional protein-based systems.
Dr Graeme Cowan - Characterising immunity to malaria
The mechanisms involved in immunity to malaria are complex and not fully understood, but it is known that antibodies play an important role. We are using and developing new next-generation sequencing and single-cell genomics techniques to characterise immunity to malaria to understand the exact nature of non-sterilising asymptomatic immunity to malaria.
By understanding the timings and contributions of different immune effector mechanisms, as well as the antigen epitopes involved, we aim to contribute to the design of an effective malaria vaccine.
Dr Nisha Philip - Signalling pathways during malaria parasite infection and transmission
My lab is interested in two main aspects of malaria biology.
- Organisation of signaling pathways during malaria parasite infection and transmission: Protein phosphorylation plays a central role in numerous signalling pathways critical to cell proliferation and development. In Plasmodium, the causal agent of malaria, protein phosphorylation is critical for its development and virulence, but the associated regulatory signalling networks are poorly understood. Using state of the art proteomic, chemical genetic and bioinformatics tools we intend to systematically define functional signaling networks regulated by phosphorylation modulating enzymes during two key stages of the malaria parasite life cycle: host cell infection and host-to-mosquito transmission.
- RNA binding proteins mediated regulation of Plasmodium development: The malaria parasite has a complex life cycle requiring both a mammalian host and mosquito vector. Almost 200 RNA binding proteins (RBPs) are expressed at distinct stages of Plasmodium life cycle where they are implicated in both parasite development, and host-to-vector and vector-to-host transitions. We recently identified a family of RBPs which play crucial roles in parasite growth in the host erythrocyte and development of the mosquito infective form. We aim to understand how these RBPs are regulated and what RNA molecules they regulate.
Professor Sarah Reece - What makes a successful parasite?
Our research focuses on malaria parasites, which are an excellent model system to study host-parasite-vector interactions, and because malaria parasites and their relatives cause some of the most serious infectious diseases of humans, livestock, and wildlife.
We use evolutionary theories and ecological principles to help us understand what parasites do during infections, and why they do things in these ways. We are evolutionary ecologists at heart but we also dabble in parasitology, chronobiology, behavioural biology, genetic modification, mathematical modelling, immunology, various ‘omics, and biophysics.
Professor Alex Rowe - What makes malaria-infected red blood cells sticky?
A unique feature of human malaria caused by Plasmodium falciparum is the ability of infected erythrocytes to bind to blood vessel walls leading to blockage of micro-vascular blood flow. This can lead to life-threatening disease due to hypoxia, acidosis, inflammatory changes, organ dysfunction and death. The aim of our research is to characterise the parasite adhesion molecules and human cell receptors and serum proteins that interact to cause adhesion of infected erythrocytes.
We focus on two adhesion types that are associated with severe malaria in young African children – rosetting with uninfected erythrocytes and binding to human brain endothelial cells. We aim to identify that receptor-ligand interactions leading to adhesion, and develop interventions to block or reverse adhesion to prevent deaths from severe malaria.
Dr Phil Spence - How do children become immune to severe malaria?
The Spence lab asks how children become immune to severe malaria. This is a key question because malaria continues to kill hundreds of thousands of children each year; parasite drug-resistance threatens malaria control worldwide; and the only licensed malaria vaccine has low and short-lived efficacy. A better understanding of the immune response to malaria is crucial to improving disease control.
Dr Joanne Thompson - Understanding host-parasite interactions at the molecular level
The malaria parasite has a surprisingly complex life cycle in its vertebrate host and mosquito vector and is capable of interacting with and invading a range of host tissues. In establishing a long-lasting infection in mammalian hosts, the parasite must also detect and respond to changes in its cellular environment and modulate the development of an effective host immune response. My primary research interest lies in exploring these host-parasite interactions at the molecular and cellular level; in particular carrying out functional analyses of parasite integral-membrane proteins that share features with G-Protein Coupled Receptors and Tumour Necrosis Factor Receptors and so are implicated in signal transduction and immunomodulation.
These studies have also recently led to the development of gene transformation technologies in Plasmodium chabaudi; the experimental malaria parasite model that most closely resembles human malaria infection. This has opened the way to directly visualize host immune cell-parasite interactions and to investigate immune responses to parasites in which candidate immunomodulatory genes have been deleted.
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