Details of Grant 

EPSRC Reference:	EP/N007700/1
Title:	Red Cell Physical Properties in Health and Disease
Principal Investigator:	Petrov, Dr PG
Other Investigators:	Winlove, Professor CP
Researcher Co-Investigators:
Project Partners:
Department:	Physics
Organisation:	University of Exeter
Scheme:	Standard Research
Starts:	01 February 2016	Ends:	30 April 2019	Value (£):	371,165
EPSRC Research Topic Classifications:	Biophysics
EPSRC Industrial Sector Classifications:	No relevance to Underpinning Sectors
Related Grants:	EP/N007719/1 EP/N007980/1
Panel History:	Panel Date Panel Name Outcome 22 Jul 2015 EPSRC Physical Sciences Physics - July 2015 Announced
Summary on Grant Application Form
The red blood cell membrane has remarkable physical properties, which are major determinants of blood flow, particularly in the microcirculation. For example, blood flow through small capillaries requires fine-tuning of membrane shape and elasticity. Many diseases are associated with impaired microvascular function which has been attributed to changes in the physical properties of the red cell membrane arising from the oxidative stress to which the cell is subjected. More recently, strong evidence has begun to appear that the RBC also plays an active role in controlling microcirculation through the release of chemical signalling agents. For example, release of ATP from red cells (which stimulates the dilation of blood vessels), is stimulated by mechanical deformation of the red cell membrane, and is compromised in diabetes. Such evidence makes clear that the physical properties of red, and other, cells play important roles in controlling biological function. In this project we will develop new experimental methodologies to analyse quantitatively the physical properties of the red cell membrane on the basis of novel computational models of membrane dynamics. We will investigate, experimentally and theoretically, the role different lipid species play in setting membrane elasticity and membrane electrical properties, how different lipid species are organised in larger formations called lipid microdomains, and how these processes are affected by oxidative stress. With the help of these insights, we will develop new computational models of the cell as a whole which, in combination with novel experimental methodologies, will enable us to accurately measure the elastic constants of the red cell. We will use these novel methodologies in the the final part of the project to investigate how the red cell membrane physical properties (elasticity, electrical potentials) affect biochemical sugnalling originating from the red cell. In these studies, we shall seek to establish whether membrane deformation, mechanical properties and/or oxidative stress affect production and release of two signalling agents, ATP (a known vesodilator) and sphingosine-1-phosphate (a signalling sphingolipid and a regulator of the vascular and immune systems). We expect that these studies will contribute to the understanding of the origin of membrane elasticity in red cells, how it is changed in disease an how it can affect biochemical signalling pathways, as well as suggest new therapeutic targets and approaches.
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Organisation Website:	http://www.ex.ac.uk