Boris Vojnovic - Overview
The Advanced Technology Development Group of the
Gray Cancer Institute 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. We 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.
We aim 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.
We are 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 our 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.
