Bionanotechnology involves manipulating and modifying components of living organisms, to generate tools on the 1-100 nanometre scale with new desirable activities. Our goal in particular is to develop new chemical and biological approaches for imaging cellular function and for diagnosis. We are applying these approaches to understand the signalling of the type 1 insulin-like growth factor receptor (IGF1R), which is involved in cell survival, differentiation and aging, as well as being an important therapeutic target in cancer.

Covalent antibodies for cellular imaging and cancer diagnosis
We have been developing a new class of antibodies/affibodies that form covalent bonds to endogenous protein targets. Even high affinity antibodies generally dissociate from their targets on the time-scale of minutes. Antibodies that do not dissociate from their targets should reduce the detection limit of tumour markers, to allow earlier cancer diagnosis. We are also applying covalent antibodies in single molecule imaging, to understand how IGF1R activates different pathways in different parts of the cell.

Quantum dots to analyse receptor traffic at the single molecule level
Most biological experiments observe the behaviour of hundreds to millions of molecules. Being able to study molecules in the cell one at a time can give dramatic new insights into the cell's function. We have developed new ways to target quantum dots (QDs), ultra-bright nanoparticles, to study cell surface receptors. In particular we have used QDs to understand the LDL receptor, which has a central role in preventing heart disease and may also be important in the capture of lipid-soluble antigens to activate the anti-tumour immune response.

Synthetic biology to map cell-cell interactions
Reductionist biology has been very good at understanding the behaviour of cells in isolation, but cells in the body are surrounded by a community of other cell-types. The behaviour of each cell is crucially regulated by mechanical and chemical inputs from its neighbours. We are engineering a new signalling pathway for stable induction of fluorescence upon cell contact, to image cell-cell interactions in vivo. A sensitive and stable reporter of specific cell-cell contact will illuminate how T cells search out and kill their targets.