Current Research

We are interested in the cellular, molecular and immunological biology of malaria parasites and other infectious diseases. Most of our work focuses on the transmission stages of Plasmodium falciparum- gametocytes- which are responsible for spreading the parasite between humans via mosquito bites. P. falciparum causes the majority of malaria episodes in sub-Saharan Africa and is more virulent than other Plasmodium species, causing severe malaria; together with malaria in pregnancy, childhood malaria remains one of the region's leading causes of mortality. We use a range of modern molecular, cell biological, transcriptomic, genomic and immunological approaches to understand fundamental parasite biology and translate this knowledge into targets for disease intervention. 

More broadly, our lab is focused on understanding fundamental infectious disease biology and immunology, with a particular emphasis on malaria. Our work centres on two main themes: 1) how human immune cells respond to infectious pathogens such as malaria parasites, in both natural infection and vaccinated individuals, and how serology can be used to detect infection and monitor vaccine responses; and 2) the molecular biology underlying infectious diseases as transmission dynamics shift with climate change, and how molecular diagnostic tools can be used to detect and quantify infections. 

At the moment, we are focusing on the following specific research areas:

Establishing CRISPR-Cas9 gene editing of malaria parasites

To move beyond correlational studies and directly test gene function, we are establishing CRISPR-Cas9-based genetic modification (transfection) of Plasmodium falciparum parasites in the lab. This capability will allow us to knock out, tag or otherwise manipulate candidate genes identified across our research programme- from those implicated in gametocyte sequestration and sex ratio determination to variant antigen expression- and directly test their function in the parasite. As an enabling technology, it underpins several of our ongoing projects rather than sitting within any single one. This work is supported by the Georg Forster Research Fellowship of the Alexander von Humboldt Foundation, in collaboration with Prof. Dr. Friedrich Frischknecht at Heidelberg University Hospital, Germany.

Malaria parasite adaptations in human tissues and whole parasite vaccines

P. falciparum gametocytes- the parasite's transmission stage- develop while sequestered in the bone marrow, but the genes controlling this process, and how bone marrow, blood and other tissues shape gametocyte development, remain poorly understood. We are studying how parasites isolated from different tissues differ in their growth, gametocyte production and gene expression, including the characterisation of slow-growing clinical isolates, to inform whole-parasite vaccine development. This work is supported by the Georg Forster Research Fellowship of the Alexander von Humboldt Foundation at Heidelberg University Hospital, hosted by Prof. Dr. Friedrich Frischknecht.

Gametocyte sex ratio determination and variant antigen expression

Malaria parasites must sense their environment to regulate gene expression- for instance, to evade immunity or to produce gametocytes at the optimal sex ratio. The underlying molecular mechanisms remain largely unknown, though available evidence points to a strong role for epigenetic regulation. We have established several parasite lines from symptomatic patients, including those with severe anaemia, and are characterising these clinical isolates to understand how sex ratio determination and variant antigen expression are regulated in the gametocytes they produce. We work closely with Prof. Oliver Billker, MIMS, Umeå, Sweden.

Antibody and cellular immune responses to Plasmodium falciparum gametocytes

The current drug of choice for acute malaria is artemisinin-based combination therapies (ACTs). ACTs reduce, but do not eliminate, gametocyte carriage, allowing some transmission to continue after treatment. Antibody responses directed at the parasite's sexual stages in the mosquito have been shown to reduce malaria transmission, whereas little is known about antibody responses to gametocytes within the human host. We and others have described distinct antibody responses that recognise gametocytes and are associated with reduced gametocyte carriage, but the target antigens remain unknown. We are using molecular, immunological and transcriptomic approaches to identify and characterise gametocyte-specific antigens, to shed light on gametocyte immunity and inform the development of transmission-blocking interventions.