Cell signalling is often triggered by specific protein interactions made by cell surface receptor proteins that are embedded within the membrane that surrounds each cell. Because receptor proteins are directly accessible to systematically-delivered drugs and the antibodies of the host immune system, they are excellent therapeutic targets used in the treatment of both genetic and infectious diseases. Identifying extracellular interactions, however, remains technically challenging because membrane proteins are difficult to work with due to their amphipathic nature, and the typically transient nature of their interactions (see PubMed ID (PMID) 19593473). The laboratory has developed technologies to identify these interactions (PMID: 18296487) and has made important contributions in understanding basic biological processes (PMID: 22180726) and infectious disease, particularly malaria (PMID: 22080952). This project aims to develop new technologies to identify novel extracellular interactions that will eventually lead to the rational design of therapeutics both for genetic and infectious diseases. The project will capitalise on very encouraging preliminary data that shows the recombinant protein probes used in the laboratory can specifically stain unknown receptors expressed on the surface of human cell lines. The approach will use the latest CRISPR/Cas9 knockout technology to molecularly identify the binding partners using a systematic and genome-wide approach. The Institute has a large human cell line resource and also a genome-wide CRISPR/Cas9 library with associated expertise that can be exploited for this project. Please contact Gavin Wright (firstname.lastname@example.org) for an informal discussion about the scope and potential applications of the technology.
- Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum. Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M, Uchikawa M, Mboup S, Ndir O, Kwiatkowski DP, Duraisingh MT, Rayner JC, Wright GJ. Nature. 2011 Nov 9;480(7378):534-7. (PMID: 22080952)
- Large-scale screening for novel low-affinity extracellular protein interactions. Bushell KM, Söllner C, Schuster-Boeckler B, Bateman A, Wright GJ. Genome Res. 2008 Apr;18(4):622-30. (PMID: 18296487)
- Recessive genetic screening with a genome-wide lentiviral CRISPR-guide RNA library. Koike-Yusa H, Li Y, Tan E, Velasco-Herrera M, and Yusa K. Nature Biotechnology 2013 Current issue DOI: 10.1038/nbt.2800