What we do

We employ and develop a range of imaging approaches and analysis tools to study individual cells in complex tissues, such as the whole ovary and organoids, to visualising key regulatory molecules dictating stem cell fate and real-time signalling in pregnant human myocytes, down to individual receptor molecules at the plasma membrane via super-resolution microscopy.  We have also developed unique mathematical and computational systems. Specifically, we employ: widefield, confocal, electron microscopy (EM), total-internal reflection fluorescence (TIRF) imaging, and super-resolution imaging techniques of structured illumination (SIM) and photo-activated localisation microscopy (PALM).

Why it is important

Microscopy has always been a fundamental tool in biological discovery; however, as our understanding has increased, so has the complexity of our questions and the need for more advanced optical tools to answer them. Critical developments in fluorescence, confocal, detectors and image deconvolution, with advances in fluorescent labels and computational image analysis, have enabled unprecedented cell biological insight and broaden the range of applications that imaging can be applied to. Furthermore, the advent of super-resolution imaging techniques has enabled biologists to track single molecules of labelled proteins down to <10nm resolution, compared to conventional light microscopy that achieves ~200nm maximal resolution. This ever-evolving area of microscopy enables scientists across broad research areas to further unlock the ‘inner secrets’ of cells; knowledge that can be harnessed and exploited in different diseases and as novel drug discovery strategies.

Impact

We are not only employing microscopy to uncover novel cell biology but also contributing to the development of cellular imaging techniques used by the life sciences. Examples of such development include work from Professor Kate Hardy and Steven Franks who have developed computational image approaches to the quantitative analysis of spatial data. Originally developed to study how signals in the ovary selectively recruit follicles for development, it is widely applicable to other spatial and patterning studies in physiology and molecular, cell, and developmental biology. The groups of Dr Hanyaloglu and Prof Huhtaniemi were the first to develop dual colour PALM using photoactivatable dyes, a technique they termed PD-PALM. PD-PALM was used to enable quantitation of the organisational landscape of cell surface G protein-coupled receptors as dimers and oligomers, and pinpoint the exact molecular makeup and spatial arrangement within an oligomeric complex by achieving a resolution of ~8nm. The custom software developed by these groups to quantitate super-resolution localisation imaging data is freely available.

Summary of current research

• Imaging G protein-coupled receptor hetero and homooligomerization by PD-PALM, led by Dr Aylin Hanyaloglu
• Trafficking of G protein-coupled receptors key in reproduction and nutrition at single event resolution, led by Dr Aylin Hanyaloglu
• Imaging G protein-coupled receptor signalling in human pregnant myometrium, led by Dr Aylin Hanyaloglu
• Visualisation of follicle growth activation in whole ovary culture, led by Prof Kate Hardy and Prof Steve Franks
• Inter-follicle signals and ovarian homoeostasis, led by Prof Kate Hardy and Prof Steve Franks
• Mechanisms underlying altered granulosa cell function in polycystic ovarian syndrome, led by Prof Steve Franks and Prof Kate Hardy
• Imaging metabolic reprogramming in pluripotent stem cells, led by Dr Veronique Azuara

Lead researchers