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NBIPI: DCU Cluster

Research - Demonstration Projects - Imaging Technology Projects

The Platform Development Programme proposes collaborative hypothesis-driven projects for integration and training of Ph D students. These projects aim to achieve integrations at 2 levels: (a) Nano - Molecule - Cell - Tissue - Animal - Human (b) Mathematics - Engineering and Physics - Chemistry - Biology - Medicine Expected deliverables and outcomes are:

DP1: Apoptosis and Cancer:

Apoptotic signalling through Bcl-2 family members: From advances in single cell imaging to new systems approaches.

PIs: Jochen Prehn (RCSI), Alan Ryder (NUIG), Robert Foster (DCU), Brian MacCraith (DCU), Heinrich Huber (SIEMENS Ireland), Peter Wellstead (NUIM), John Morrison (UCC), Paul Whelan (DCU), Hugh Byrne / Fiona Lyng (DIT)
Core Support: Molecular/Cellular, Image Technology (IMMT, Image Processing & Analysis)
Description: Bcl-2 family proteins signal cellular life and death decisions. This research programme will deliver new insights into the temporal and spatial dynamics of Bcl-2 family protein activation and interaction at the single cell and single molecule level, employing established GFP imaging, FRAP and FRET imaging, as well as novel FCCS and FLIM techniques. Using these data sets, it will deliver new computational models and hypothesis that will be tested subsequently in imaging experiments. This programme will also deliver novel application-optimised, chemically sensitive fluorophores and microfluidic nanodevices that will greatly advance quantitative imaging approaches by providing increased signal to noise ratio and by extending the number of observable parameters and protein interactions. In a complementary strand, novel spectroscopic imaging tools for cancer diagnosis will be developed by identifying unique spectral fingerprints of normal, abnormal and precancerous cells.

DP3: Neuroscience:

Visualization and image analysis of neural injury, plasticity and repair.

PIs: David Henshall (RCSI), Manus Ward (RCSI), David Finn (NUIG), Kieran McDermott (UCC), Tia Keyes (DCU), Patrice Mollard (CNRS), Mark Redmond (Our Lady's Hospital for Sick Children), Paul Whelan (DCU), Martin Plucht (SIEMENS Ireland), Dimitris Kalamatianos and Peter Wellstead (NUIM)
Core Support: Molecular/Cellular, Animal, Image Technology (Image Processing & Analysis, IMMT); Human vascular ultrasound Imaging; Image
Description: Emerging data show neuronal microstructures and synaptic contacts are highly plastic, undergoing rapid or long-term adjustments in response to neuronal insults and in the setting of neuronal degeneration. This research programme will apply in vivo imaging tools to investigate responses to ischemic, traumatic and epileptic brain injury to elucidate contributions to chronic conditions such as epilepsy and neuroendocrine disorders. It will also investigate which changes contribute to long-term plasticity and repair during chronic pain and neurodegeneration. In a complementary research strand development and repair processes elicited by neural stem cells will be described ex vivo in real time, and mathematically modelled to determine how intrinsic and micro-environmental factors influence lineage decisions relevant to such repair processes. Using established organotypic slice cultures in vitro and rodent models of cerebral ischemia, pain, trauma and seizures in vivo, this research programme will employ two-photon microscopy, intravital fluorescence microscopy and GFP reporter mice to capture and analyse images of degenerative and restructuring changes and intracellular metabolic and energetic responses in intact CNS structures and in 3 dimensions. These changes can then be contrasted with the human brain following seizures, pain, trauma and stroke in collaboration with the TCIN MRI facility of the BMSN network, and can identify processes that may be of therapeutic and diagnostic significance.

DP4: Cardiovascular Research

Dynamic changes during thrombosis and atherogenesis.

PIs: Niamh Moran (RCSI), Alice Stanton (RCSI), Noel Caplice (UCC), Dermot Kenny (RCSI), Robert Forster (DCU), Tia Keyes (DCU) Brian MacCraith (DCU), John Morrisson (UCC); Patrick Harriott (QUB), Paul Whelan (DCU)
Core Support: Molecular/Cellular Imaging; Animal imaging; Human vascular ultrasound Imaging; Image Technology (Image Processing & Analysis)
Description: Thrombosis superimposed on atherosclerosis accounts for 45% of total mortality worldwide. This research programme will further investigate the role of the platelet in thrombosis and atherogenesis, inter-individual differences in these processes, and responses to therapy. Critical thrombotic events will be assessed ex-vivo in human platelets using a unique high-throughput platelet profile assay, microfluidic live-cell imaging techniques and Raman, resonance Raman and Infra-red microscopy combined with statistical cluster analysis, allowing for the first time, dynamic shifts in cell-surface proteins to be recorded on time scales ranging from minutes to microseconds. Molecular ultrasound imaging and CT-PET will be used to visualize, in animal models and in man, the profile of the platelet in early atherogenesis and plaque progression. Using novel bio-mimetic peptides, coupled to unique environmentally-sensitive luminescent ruthenium, osmium and iridium dyes with very long-lived excited states, this program will utilize established FRET imaging techniques, and will develop FLIM and resonant Raman technologies, to enhance the understanding of temporal and spatial events that co-ordinate platelet activation, adhesion and aggregation in haemostasis and thrombosis. Such novel sensitive phenotyping tools, when combined with chemistry and proteomic approaches, will assist in the characterization of a prothrombotic platelet profile and will facilitate the development of novel diagnostic tools ultimately finding application in theranostics.

DP5: Vascular disease

New diagnostic tools and targeted therapeutics of acute myocardial infarction.

PIs: Noel Caplice (UCC), Alice Stanton (RCSI), Timothy O'Brien (NUIG), Frank Barry (NUIG), Cathal Kelly (RCSI), Chris Dainty (NUIG), Martin Leahy (UL) Stephanie Dimmeler (Frankfurt University), Paul Whelan (DCU)
Core Support: Animal Imaging (large & small animal), Human Imaging (vascular ultrasound), Imaging technology (adaptive optics, image processing and analysis, compute node, tissue viability imaging)
Description: 45% of the world's population dies a cardiovascular death. Currently two major challenges confront vascular researchers and clinicians, namely, the precise quantification of individual cardiovascular risk non-invasively in large populations, and the maximum salvage of tissue in those suffering an acute event, either myocardial infarction or stroke. In this programme, novel diagnostic tools which quantify the earliest structural and functional changes in small and large arterial vessels, as markers of risk, will be developed and evaluated. Enhanced resolution retinal imaging and specialist skin microcirculation imaging techniques (optical coherence tomography, laser Doppler perfusion imaging and tissue viability) will allow study of the microvasculature in diabetes. Four dimensional, tissue Doppler, contrast and molecular ultrasonic imaging will be used to quantify large artery endothelial function, wall stiffness and early atherosclerosis. Controlled organ specific drug delivery can be achieved through ultrasonic rupture of echogenic microparticles filled with pharmacological agents. We will test in an animal model the hypothesis that ultrasonic-mediated delivery of thrombolytic therapy during acute myocardial infarction will reduce both myocardial damage and bleeding complications. In a further attempt to limit damage and enhance repair, the efficacy of autologous mesenchymal stem cell therapy in a large animal model of acute myocardial infarction will be tested. The mechanism of benefit and efficacy of treatment will be determined by sophisticated CT-PET imaging with real-time in vivo tracking of stem cells and with in vitro genetic tracking of cells. These two studies will be expected to deliver data sets which can be used for regulatory authorization of clinical trials of thrombolytic filled micro-particles and mesenchymal stem cells in myocardial infarction in humans.