Borivoj Vojnovic Overview
The Advanced Technology Development Group of the Gray Institute for Radiation Oncology and Biology aims to develop state-of the-art instrumentation and processing methods used in the development of a range of biological and clinical assays associated with radio- and chemo-therapy. In particular advanced imaging methods based on spectrally and temporally-resolved imaging are applied to the understanding of cell signalling pathways using fluorescence resonance energy transfer methods. Three-dimensional imaging of responses to vascular targeting agents is applied with MRI/MRS techniques and with multiphoton, confocal and structured light optical methods. Complementary automated image processing methods are developed to extract information of interest e.g. for understanding the structure of tumour vascular networks in 3-D, monitoring the changes that occur during tumour growth and following therapy. Professor Vojnovic and the group develop and apply techniques to characterise the physiological consequences of vaso-active drugs, in particular permeability of the vessel wall, red blood cell velocity and tumour oxygenation status. The group aims to determine 3-D metabolic gradients of tumours, in vivo, using optical intensity-independent means of contrast (e.g. fluorescence lifetime and/or anisotropy).
Non-invasive fluorescence detection apparatus capable of imaging distributions of biologically relevant molecular species within intact biological material is also under development as are invasive methods based on fibre-optic technology.
The group is investigating methods for photochemical generation of specific radicals in model vesicles, specific cellular compartments or extra-cellularly, with the aim of assessing the importance of compartmentation of free radical reactions in cellular oxidative stress in determining the overall biological effects.
Methods to automate and quantify microscopic images are also developed. These are applied to molecular markers in histological material to predict patient response to radio- and chemotherapy. Proliferation, hypoxia and vascularity are quantified in multiply-stained sections and used as clinical treatment response indicators.
The demand for higher accuracy in sensitive single-cell and clonogenic cell-survival assays is driving the group's research into to faster and more automated cytometry systems. These are applied to targeted micro-irradiation techniques, to methods to evaluate DNA damage e.g. 'comet' assays and investigations of chromatin redistribution in the cell nucleus through spectral and texture analysis.