Previous and Current Research
We develop, maintain and provide advanced light microscopy techniques for the London Research Institute. The techniques include laser scanning confocal microscopy allowing multiphoton excitation with time correlated single photon counting, real-time Nipkow disk confocal system, digital low light level fluorescence video microscopy and image-based high content screening with robotics. Our main research project is focused on the roles of cell motility in metastasis.

In order to study this process we have been using as our model, a set of sarcoma cell populations derived from inbred rats by spontaneous transformation and subsequent tumour progression. Specifically, we have evaluated the chemotaxis of the sarcoma cell populations with different ability to shed spontaneous metastases and have investigated the roles of some molecules related to the cytoskeleton and signalling. To facilitate this, we developed and established quantitative light microscopy techniques for the objective comparison of speed, chemotaxis and intracellular dynamics of molecules. In order to identify further candidate genes potentially involved in metastasis, we carried out comparative microarray expression analysis.

We have also been involved in collaborative projects looking at intracellular transport of mRNA and of internalised receptor c-Met. Intercellular translocation of small molecules was explored in another collaborative project studying functional consequences of disease-associated connexin mutations. Our interest in chemotaxis is mainly focused on its role in metastasis but we have also studied defects in chemotaxis of macrophages.

Future projects
We plan to perform functional assays for a selected subset of candidate genes from the microarray analysis of sarcoma cell populations with different metastatic potential. The functional assays will include time-lapse analysis of motility and chemotaxis as well as dynamic studies of intracellular distribution of the chosen proteins including their interactions. In order to visualise the specific proteins, we will use nuclear microinjection of cDNA constructs to express the chosen proteins fused to biofluorescent proteins.