Much of today’s knowledge of cell biology and disease mechanisms has been obtained through molecular biology techniques, such as chromatography and Western blotting, that identify specific proteins and their interactions through chemical interactions with cell extracts in solution phase, or other biochemical analysis techniques including  NMR and mass spectrometry. These techniques, however, do not yet routinely provide single cell sensitivity but rather yield an analysis of cell populations. They have typically been complemented by microscopy of cells cultured in thin layers – typically one cell thick – on coverslips.  Such samples are highly amenable to optical imaging with high resolution and have provided information about cellular structures. Solution phase assays with optical readouts have been implemented in multiwell plates for highly parallelised, high throughput experiments able to automatically measure millions of samples. This has been heavily exploited in drug discovery to screen large libraries of compounds to identify drug candidates that have the desired biochemical effect. More recently, high content analysis platforms have been developed to automatically image cells with high throughput and provide readouts based on cell phenotype that utilise subcellular resolution. There is also increasing interest in exploiting microfluidics technology to increase the sensitivity and reduce the cost of solution-phase assays, e.g. for point of care applications. Although most of our biophotonics development concerns imaging technology, we have also applied multidimensional fluorescence techniques to cuvette and microfluidic-based measurements in solution.

Increasingly, sophisticated fluorescence labelling techniques are being applied to cell microscopy to permit single cell analysis of protein interactions, e.g. using FRET, and spatiotemporal dynamics of cell signalling and other processes, are being studied in fixed and live cells. These can include metabolic changes, which can be probed using label-free readouts of intracellular autofluorescence. Advances are being driven by innovation in imaging techniques, in software tools and particularly in approaches to labelling samples. In the Photonics Group we work on a wide range of cell imaging techniques and typically apply these capabilities to biological questions in partnership with colleagues from the life sciences. In terms of technology development, we are particularly interested in super-resolved microscopy, in automated high content analysis and in the translation of cell biology readouts to preclinical and clinical studies.

The following are some specific topics or projects in cell biology that we have addressed as part of our mission to understand the mechanism of disease in order to further the development of therapies:

Specific Topics or Projects