Sanger Institute Malaria Programme

The Sanger Institute Malaria Programme uses genomic, genetic and proteomic approaches to tackle fundamental questions in malaria biology and to discover host-parasite interactions that are critical for drug and vaccine development.

The Sanger Institute Malaria Programme has recently expanded from its long-standing leadership role in Plasmodium genome sequencing to incorporate large-scale field and lab studies, and is a key part of the Institute's research in Pathogen Genetics.

[Genome Research Limited]

Malaria

Mosquitoes carry Plasmodium parasites that cause one million deaths each year, often in children under the age of five in sub-Saharan Africa.

Mosquitoes carry Plasmodium parasites that cause one million deaths each year, often in children under the age of five in sub-Saharan Africa. [Wellcome Library, London]

Malaria is a debilitating and sometimes fatal illness that is caused by infection with Plasmodium parasites and is passed between people by mosquitoes. There are nearly half a billion cases of malaria each year, and more than one million deaths, largely in children under the age of five in sub-Saharan Africa.

There is currently no vaccine that can protect against malaria. There are effective drugs, but Plasmodium parasites are known to rapidly develop drug resistance and there are fears that they are already developing resistance to artemisinin, a drug released less than ten years ago that is currently being widely used. Developing an effective malaria vaccine and fighting anti-malarial drug resistance are among the major global public health challenges.

Malaria genomes

The genome

Sequencing the genome of Plasmodium falciparum, the parasite that causes almost all deaths from malaria, was one of the earliest projects embarked on at the Sanger Institute. Genome sequences are critical in the fight against infectious organisms because a genome sequence defines all the genes that an organism needs to survive. The Plasmodium falciparum genome sequence therefore defines all the possible genes that could be targets for anti-malarial drugs and vaccines, and has helped researchers all over the world search for new treatments.

Natural genetic variation

Recent changes in technology now allow us to move from sequencing a single genome to sequencing the genomes of large numbers of parasites obtained directly from human infections. This allows us to ask whether specific gene variants are associated with certain outcomes, such as identifying genes associated with drug resistance. The same approach can be used to identify mosquito genes associated with insecticide resistance, or human genes associated with protection against severe malaria. The Sanger Malaria Programme is working with researchers from all around the world to power these new studies.

Experimental genetic manipulation

Genome sequence can also be used to drive biological research. Many of the genes in the Plasmodium falciparum genome have no known function, making it impossible to target them. Experimental genetic approaches, from eliminating individual genes to measure the impact on parasite growth to designing novel technological approaches to screen for gene function, all depend on Plasmodium genome sequences. Members of the Sanger Malaria Programme are employing these new technologies to try to increase the scale of Plasmodium experimental genetics and therefore to increase the speed of research.

Research teams

Matt Berriman leads the Programme's efforts in Plasmodium comparative genomics, identifying genomic features that are conserved across Plasmodium species, or are unique to specific species. These investigations reveal valuable insights into host-parasite biology, and shed light on mechanisms of host specificity and virulence. Berriman Group Research Interests.

Plasmodium parasites have complex life-cycles, shuttling back and forth between humans and mosquitoes. Oliver Billker's team makes use of that fact that all aspects of this life cycle can be recreated in the lab using rodent malaria parasites, allowing access to biological questions that can't be addressed in human Plasmodium parasites. Oliver's team uses systematic genetic modifications of the Plasmodium and mouse genomes to understand parasite gene function and mechanisms of host resistance and drive the hunt for new therapies. Bilker Group Research Interests

Dominic Kwiatkowski's research is rooted in large-scale clinical and epidemiological studies in malaria-endemic countries, and makes extensive use of recent changes in DNA sequencing technology to investigate natural genetic variation in human, parasite and mosquito genomes. Dominic's group seeks to empower public health policy by developing new technological and informatics platforms that will be readily accessible not only by malaria researchers, but also by personnel on the front lines of the fight against malaria. Kwiatkowski Group Research Interests

Chris Newbold, who also has an active research group in Oxford, is an honorary faculty member in the Sanger Malaria Programme, and his expertise plays a key role in the comparative genomics effort, as well as in other areas.

The group led by Julian Rayner investigates the details of human-parasite interactions during the stage of the parasite life-cycle when the parasite infects human red blood cells, which is the stage that causes all the symptoms of malaria. Julian's group is particularly focused on how Plasmodium parasites recognize and then invade human red blood cells, and whether that process can be blocked with new vaccines or drugs. Rayner Group Research Interests

Gavin Wright leads the Sanger Institute Cell Surface Signaling team, and has a particular interest in understanding the protein-protein interactions that are responsible for communication between cells. Gavin works with several other members of the Malaria Programme to apply new protein-protein interaction technologies to understand how Plasmodium parasites interact with their hosts, both human and mosquito, and to identify new interactions that could be targeted by new interventions.

Group leaders

Matt's photo Matt Berriman
Matt's group

Oliver's photo Dr Oliver Billker
Oliver's group

Dominic's photo Prof Dominic Kwiatkowski
Dominic's group

chris's photo Chris Newbold
Chris' group

Julian's photo Dr Julian Rayner
Julian's group

Gavin's photo Dr Gavin Wright
Gavin's group

* quick link - http://q.sanger.ac.uk/ov057djl