Overview
Current Research Interests
Biophysics of the Extracellular Matrix
The extracellular matrix is a component of all mammalian tissues and consists of a network of fibrous proteins, elastin and collagens, embedded in a viscoelastic gel rich in high molecular weight anionic polymers known as proteoglycans. This structure, which is quantitatively a major component in tissues such as cartilage, intervertebral disc and blood vessels, endows tissues with the requisite mechanical properties and regulates the movement of water, nutrients and other solutes. There is strong evidence that changes in these functions are associated with diseases as apparently diverse as arthritis, atherosclerosis and cancer. There is a delicate symbiosis between the behaviour of the cells, whose functions include the repair and remodelling of the extracellular matrix, and the composition of the matrix itself. This interaction, which is mediated by a wide variety of electrical, mechanical and chemical signals, is only slowly becoming understood but it underlies the normal processes of development and growth and may be impaired in disease.
Our research has the long-term aim of unravelling the relationships between the physical properties of the macromolecular constituents of the extracellular matrix and their supramolecular assemblies and the physiological functions of the tissue. This information is, we believe, important in relating the wealth of descriptive data that has accumulated on changes in extracellular matrix biochemistry that occur in disease to the actual disease process.
Current projects include:
- Analysis of the molecular mechanisms of elasticity in elastic proteins.
- Characterisation of the organisation of Type IV collagen in the basement membrane and the changes that occur in diabetes.
- Investigation of the structure and permeability to nutrients of the bone-cartilage interface in normal tissues, osteoporosis and arthritis.
- Ultrastructural analysis of the stress and strain distribution in bone and cartilage under mechanical loads.
- Investigation of the effects of ionising radiation on the physical properties of extracellular matrix macromolecules.
In this work we employ techniques such as Raman microspectrometry to characterise molecular composition and conformation, small and large angle X-ray diffraction, utilising synchrotron sources, to characterise intra- and supra-molecular organisation and X-ray fluorescence for material characterisation, as well as a number of more specialised techniques, some of which are described in the Biophotonics section.
Biophysics of the vasculature
The microcirculation consists of a network of blood vessels less than100µm in diameter. The structure of the network varies between organs, but it is highly adapted to effect the efficient exchange of nutrients and metabolites between blood and tissue. The flow of blood is influenced by its particulate nature, by interactions with the vessel wall and from the ability of the vessels to change their calibre in response to nerve, chemical and even fluid mechanical signals. There is also a lymphatic circulation into which fluid and solutes passing through the capillary walls into the extracellular matrix is drained and pumped, though a series of "lymph hearts", back into the systemic circulation. Our group is concerned with biophysical aspects of normal microvascular function and, increasingly, with the abnormalities associated with conditions such as diabetes and sepsis.
Current research includes:
- Studies on microvascular permeability and haemodynamics, particularly in relation to diabetes.
- Investigation of the effects of fluid mechanical forces on endothelial cells.
- Characterisation of the microcirculation and haemodynamics of the equine foot and its contribution to venous return.
- Theoretical and experimental studies on flow in lymphatic vessels.
- The effects of ultrasound on the vessel wall
Much of this work is carried out in collaboration with colleagues at the Medical School and derives support from experimental techniques developed by the Biophotonics Group.
Membrane Biophysics
My work on membrane biophysics is largely conducted in collaboration with Peter Petrov and is more fully described on his website. In brief, we are now employing a range of physical methods for measuring mebbrane properties toinvetigate changes associated with clinical conditions ranging from diabetes to oxidatvie stress, linking to the active programme of research in these areas at the Medical School. We also collaborate with colleagues in Bioscience in studying the mechanisms of interaction of bacteria and bacterial toxins with the cell membrane.
Biosensors
My long standing interest in electrochemical methods of measuring biologically important analytes in living tissue is currently focussed on the detection of markers for sepsis, in collaboration with clinical colleagues. The research also extends to combination of electrochemical methods with optical sensing, currently in collaboration with members of the Graphene Centre and my colleague Dr Steve Green.
Education
B.Sc (Physics) Imperial College 1970
M.Sc. Applied Mathematics Oxford 1971
D. Phil Quanitsation of General Relativity Oxford 1974
Previous Posts
1995-99: Reader in Connective Tissue Biophysics, Imperial College, London
1988-95: Wellcome Trust Lecturer, Physiological Flow Studies Unit, Imperial College
1982-888: BP Venture Research Fellow, Honorary Lecturer, Imperial College
1979-82: Wellcome Trust Senior Research Fellow, Imperial College
1976-1979: MRC Training Fellow, Imperial College
1974-76: Research Fellow, Medical Physics Dept, Hammersmith Hospital
Current External Appointments
Back to Back: Committee Member
Southwest Institute of Biosensing Technology: Advisory Board
MOAC Doctoral Training Centre, Warwick: Advisory Board
Agence Nationale de la Recherche: Overseas expert advisor
Research Council of Hong Kong: Overseas advisor
British Israel Research and Academic Exchange Programme in Regenerative Medicine: Selection panel member
Current Research Grants
Arthritis Research UK: Characterisation of the structure and mechanical properties of the superficial zone of articular cartilage. £104k
British Heart Foundation: Structure/Function relationships in small vessels in health and disease £186k
Diabetes UK: Subcellular deposition of fatty acids in b-cells revealed by non-linear microscopy. £145k
DSTL: Effects of bacterial toxins on host cell membrane biophysics £325k
Facilities Usage
STFC: The structure of the lipid layer of the pre-occular tear film. Diamond (4 days)
Conference Organisation
UK-Israel workshop on cellular and molecular bioengineering and biophysics (2008)
Advanced photonic techniques in biology. IOP (2008)
First international biosensing technology conference (2009)
Advanced biophotonics IOP (2011)
Advanced photonics techniques in biology IOP (2013)
Second international biosensing technology conference (2013)
Contributions to the Community
BA Festival of Science 2009: Invited Lecture "The Physics of Life"
Talks at British Heart Foundation and Arthritis UK public and fund raiser awareness events.
