Cell Surface Signalling Laboratory
The Cell Surface Signalling Laboratory is interested in identifying new therapeutic targets for both genetic and infectious diseases by using large-scale systematic approaches to discover receptor-ligand interactions that are essential for cellular recognition processes. Molecular interactions involved in cellular recognition events are typically very weak (often having monomeric half-lives of just fractions of a second) and so we have developed bespoke approaches that require creating highly avid soluble recombinant proteins to detect these fleeting binding events. The laboratory has identified interactions that are essential for basic biological events of fundamental importance which notably include sperm-egg recognition in mammals, and the invasion of erythrocytes by the blood stage of Plasmodium falciparum - the parasite responsible for most clinical cases of the deadly infectious diseases, malaria.
The focus of our research is the molecules which are displayed on the surface of cells, and in particular, the extracellular binding events that they mediate. Extracellular interactions are excellent therapeutic targets because they are directly accessible to systematically delivered drugs such as monoclonal antibodies. For infectious diseases, proteins displayed on the surface of pathogens are good vaccine candidates because vaccine-elicited antibodies can destroy or disable the pathogen.
We use a mammalian expression system to produce large panels of soluble recombinant proteins to increase the chances that the proteins will be correctly folded and active; the proteins are then used for protein interaction and preclinical vaccine screening. We have developed infrastructures that allow us to express and purify many hundreds of recombinant proteins expressed in this system rapidly and conveniently.
New methods to identify low affinity extracellular receptor-ligand interactions
We have invented and continue to develop methods for large scale extracellular interaction discovery such as our AVEXIS technique. Currently, we are developing genome-scale receptor screening systems based on both creating transfected cellular microarrays, and collaborate with other teams at the Institute to use genetic approaches based on the CRISPR-Cas9 method. One unifying aspect of these methods is that we are expecting extracellular interactions to be very weak, and so we purposefully increase binding avidity when performing our receptor interaction screens experiments by oligomerising the protein probes.
Systematic preclinical vaccine screens for neglected tropical diseases
We use our mammalian expression technologies to create panels of recombinant pathogen proteins that are then used to identify new subunit vaccine targets for infectious diseases. We have compiled a large panel of proteins representing the cell surface receptor repertoire and secreted proteins from the blood stage of the malaria parasite.
These proteins can be comparatively tested to identify the most promising vaccine candidates, and to understand how the parasite interacts with the human host and cause disease. As well as malaria, we are working on other parasitic diseases including schistosomiasis, leishmaniasis and trypanosomiasis – infectious diseases that affect some of the most disadvantaged people in world.
Videos of some of our research
Dr Gavin J Wright
Senior Group Leader
Gavin is interested in the molecular basis of cellular recognition events. The goals of his research are to obtain a mechanistic understanding of how cells interact both within our own bodies and with pathogens. Ultimately, this knowledge will inform the rational design of intervention strategies for the treatment and prevention of genetic and infectious diseases.
We seek to explore the vast cellular diversity in the human brain using large-scale spatial transcriptomics, imaging and functional screens.
The Parasite Genomics group uses comparative and functional genomics approaches to investigate the biology of helminths and protozoan parasites.
Natural genetic variation
The Kwiatkowski group investigates Plasmodium, Anopheles and human genome variation in large clinical and epidemiological studies carried out with partners in ...
Rodent models of malaria
At the Sanger Institute Oliver Billker's group used experimental genetics in rodent models to study the basic biology of ...
Programmes and Facilities
We develop and enhance high-throughput tools and technologies for malaria research to enable us to understand specific biological problems relevant for ...