Details of Grant 

EPSRC Reference:	GR/S69801/01
Title:	A Multi-Disciplinary Study of New Blood Vessel Formation, An Emergent Tissue-Level Phenomenon
Principal Investigator:	Schor, Professor S
Other Investigators:	King, Professor J
Researcher Co-Investigators:
Project Partners:
Department:	Pathology and Neuroscience
Organisation:	University of Dundee
Scheme:	Standard Research (Pre-FEC)
Starts:	01 October 2003	Ends:	31 March 2004	Value (£):	30,075
EPSRC Research Topic Classifications:	Complexity Science Tissue Engineering
EPSRC Industrial Sector Classifications:	Healthcare
Related Grants:
Panel History:
Summary on Grant Application Form
Angiogenesis, ie. the process of new blood vessel formation, is an intrinsically complex tissue-level phenomenon. In order to simplify experimentation, biologists commonly described angiogenesis in terms of a sequence of discrete events including (i) the activation of endothelial cells lining the lumen of tissue microvessels by a soluble angiogenic factor, (ii) the migration of the activated cells through the vessel basement membrane into the surrounding 3-dimensional tissue matrix, (iii) the directed migration (chemotaxis) of these extra-vascular endothelial cells towards the source of the angiogenic factor, and (iv) the morphogenetic interactions of the extra-vascular endothelial cells to form multi-cellular aggregates,these eventually producing patent microvessels in functional contact with the parent vessel. The application of standard cell and molecular biological techniques have led to the identification of numerous chemically unrelated pro- and antiangiogenic factors. It is now clear that the inception, directionality and cessation of angiogenesis is mediated by the relative balance of multiple stimulators and inhibitors, rather than the action of a single factor. Biologists now additionally recognise that the 3-dimensional extracellular matrix in which the extra-vascular endothelial cells are embedded also makes a major contribution to the control of angiogenesis, as do other tissue-level parameters, including oxygen tension and mechano-chemical signal transduction.Much is known about the mechanisms whereby soluble angiogenic factors and inhibitors interact with individual endothelial cells in terms of (i) the identity of their cell surface receptors, (ii) the signal transduction pathways they induce, and (iii) the resultant effects of these biochemical pathways on endothelial cell gene expression. Unfortunately, reductionist logic based on these cell- and molecular-level data cannot be used to understand angiogenesis in terms of the complex temporal and spatial parameters (eg. gradients of effector molecules, matrix remodelling) which regulate endothelial cell movement and morphogenetic interactions at the tissue level. In order to address this need, the proposed sandpit will bring together biologists interested in understanding the tissue-level control mechanisms operative in angiogenesis, physical scientists who can provide the necessary collaborative expertise required to address this complex biological problem, and clinicians with expertise in monitoring angiogenic activity in human subjects and the multi-factorial nature of angiogenesis control in vivo. The expected final outcome of the sandpit will be the identification of a small number of multi-disciplinary research programmes/networks which will be submitted to the EPSRC for funding.
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Organisation Website:	http://www.dundee.ac.uk