School of Veterinary Medicine and Science
   
   
  
 

Image of Cyril Rauch

Cyril Rauch

Associate Professor in Physical and Mathematical Veterinary Medicine & Science, Faculty of Medicine & Health Sciences

Contact

  • workRoom B77 Veterinary Academic Building
    Sutton Bonington Campus
    Sutton Bonington
    Leicestershire
    LE12 5RD
    UK
  • work0115 951 6451
  • fax0115 951 6440

Biography

Cyril Rauch obtained his BSc, MSc and DEA from the University of Jussieu (Paris - France) followed by his PhD from the Curie Instituteand University of Jussieu (Paris - France) devoting his time on the biophysics of the cell membrane . He then spent 3 years at the Royal Veterinary College (London - UK) working on mechanotransduction and one year at the School of Pharmacy and Pharmaceutical Science of the University of Manchester (UK) working on a new detection method regarding drug/cell interactions. Finally he joined the School of Veterinary Medicine and Science (University of Nottingham) in September 2006 to set up a group focusing on the Physical and Mathematical sides of Veterinary Medicine and Science.

Expertise Summary

Applied mathematics

Physics

Cell biology

Teaching Summary

Preliminary Year - Maths

First Year - Neurology

Second Year - GI

Third Year - Research Projects

Research Summary

Graduated (BSc, MSc, DEA) in physics and applied mathematics from the University of Jussieu (Paris - France) I did a PhD (1997-2001) at the Curie Institute (Paris - France) on the physical biology of… read more

Selected Publications

Current Research

Graduated (BSc, MSc, DEA) in physics and applied mathematics from the University of Jussieu (Paris - France) I did a PhD (1997-2001) at the Curie Institute (Paris - France) on the physical biology of the cell membrane. I then went on to acquire teaching experience giving lectures in probability and statistics (IUT of Meaux/France - 2001-2002) and postdoctoral experiences in biology at the Royal Veterinary College in London (2002-2005) and drug delivery at the University of Manchester (2005-2006, School of Pharmacy and Pharmaceutical Sciences) . In 2006 I joined Nottingham Veterinary School.

My research is centred on the physical and mathematical modelling of complex biological processes/systems especially those involved in diseases. These include:

  1. Pharmacokinetics and drug delivery including molecular promiscuity
  2. Cancer including cancer cell metabolism/growth and drug resistance
  3. Appendage conditions including lameness in equine/bovine species, beak over growth in birds and nail conditions in humans
  4. Preterm delivery in humans

In each research area I always make sure that the theory is connected to a strong experimental research/input. In this context I am involved in national or international collaborations to develop life-science interface projects. Present / past collaborations are / have involved: University of Manchester (UK), ENS-Lyon (France), University of Nice (France), University of Rennes (France), University of Tours (France), University of Munster (Germany), University of Bari (Italy), Institute of Health (Roma / Italy), Institute of Clinical Biology and Metabolism (Vitoria / Spain), Vertex Pharmaceuticals.

List of funders (past/present) for my research: Medical Research Council, Vertex Pharmaceuticals, Pet Plan, Royal College of Veterinary Surgeons.

Past Research

My past research focused strongly on biomembranes, particularly membrane proteins, as very little was known about the biophysical properties of the bilayer lipid, particularly in relationship to the cell entry and transport mechanisms for drugs/therapeutics, steroid hormones, pathogen toxins (e.g. AB5), intracellular bacteria (e.g. TB) and envelope viruses (e.g. HIV, Influenza). Moreover, how these biophysical properties intrinsic to every lipid phase were directly or indirectly harnessed by cells to control genes transcription and the fate of cells was unclear, and whether they are involved in diseases (e.g. type 2 diabetes, cancer) was not yet established. However, as the frontier between the inside and the outside of living organisms, the biophysical properties of biomembranes (i.e. elastic/surface tension and bending properties) are implicated in controlling signals exchange (e.g. cytokines) with the surrounding medium, and membrane curvature is involved in endocytosis, exocytosis and intracellular trafficking. Therefore a better understanding of the membrane bilayer/lipid phase involvement was central in complex biology and needed for its exploitation in the biotechnology and pharmaceutical industries. My past research interests were contrated on:

Fluid phase endocytosis: Three type of endocytosis have been distinguished in cells; clathrin, caveolae and passive endocytosis, the latter is also known as fluid phase endocytosis (FPE). In contrast to caveolae or clathrin endocytosis, fluid phase endocytosis does not involve the formation of "coats" and for this reason has remained uncharacterised at the molecular level for a long time. However, in 1984 studies led by Devaux's group demonstrated that, in erythrocytes, the incorporation of phosphatidylserine (PS) into the outer leaflet is followed by its rapid relocation into the inner leaflet via the aminophopholipid translocase. In 1999 Farge et al. discovered that, in cells (K562), the addition of PS into the outer leaflet of the cellular membrane is not only rapidly followed by its translocation into the inner leaflet, but also increases linearly the kinetic of FPE as a function of the amount of PS relocated into the inner leaflet. Based on these observations, a simple model of FPE has been developed and validated experimentally (Rauch&Farge, 00). In simple words there is a lipid number asymmetry between the membrane leaflets, the inner leaflet containing more phospholipids than the outer one, which creates a mechanical couple that bend the membrane of cells creating vesicles.

For more information read: Seigneuret M & Devaux P, PNAS, 1984; Farge E et al., AJP cell physio, 1999; Rauch C & Farge E, Biophys. J, 2000.

Fluid phase endocytosis is involved in the control of gene transcription: The fundamental role of endocytosis is to down regulate cytokine-receptor complex formed at the plasma membrane. As FPE relies, at least in part, on specific biophysical properties of bilayer membranes, it may well be that impairing these properties is likely to affect the cytokine-dependent gene transcriptions. To test this assumption, BMP2 (Bone Morphogenetic Protein 2) which is a morphogene known to transdifferentiate muscle to bone has been used. Alteration of FPE has been performed using biophysical methods. Overall both acceleration and amplification of the transdifferentiation have been observed, suggesting that the biophysical properties of the membrane are important in cytokine-related gene transcription. (Rauch C et al., AJP, 2002)

Linking the membrane composition and the intracellular pathway related to glucose metabolism: Today, studies point out that an alteration in the metabolism of phospholipid may be key to understand the close link existing between insulin resistance and obesity. Such an idea is closely related to the fact that in Type-2 diabetes, an excess of fatty acid (from rich fat diets), once transformed into phospholipids impairs the insulin-signaling pathway. A simple assumption is that such an excess in phospholipids could alter the tensional force of the plasma membrane, potentially impairing the cellular responses triggered by specific hormones (i.e. Insulin and IGF-1). As Skeletal muscle accounts for ~70% of glucose disposal and the membrane of skeletal muscles of type 2 diabetic patients display an increased amount in phosphatidylcholine (PC), an investigation has been led to determine how an acute change in the composition of plasma membrane phospholipids, via addition of PC into the outer leaflet, may affect the intracellular pathway linked to glucose metabolism. (Rauch C & Loughna PT, J. of Cell Physio and biochem, 2005)

Linking endocytosis to Lipinski's 2nd rule with regard to the drugs' size (or MW) selectivity on their permeation across cellular membranes: To overcome the cellular barriers and ultimately interfere with their specific intracellular targets, therapeutics/drugs rely on their affinity with their targets as well as their ability to cross cellular membranes. An increasing number of studies point out that the size of drugs, or MW, might well be determinant in their transmembrane movement. In this context, experimental and computational approaches have been used to estimate what physico-chemical characteristics should have the "best" drug. From these studies, four rules have emerged ("the rule of 5"), defining drug properties for maximum efficiency. Among them is the second rule stating that a drug must have a MW equal or lower than 500, which invokes possible physical/mechanical effects related to the interaction between the size of drugs and the membrane. Based on the fact that that the inner leaflet of cells is compressed, such a compression may impair the transbilayer movement of drugs as a function of their size. As a result a theoretical analysis has been performed to determine whether the FPE may explain Linpinski's 2nd rule. Remarkably, FPE provides a very good explanation of this rule since a compression of the inner leaflet triggering membrane buds formation of radius ~50nm, matches the critical MW found by Lipinski . (Rauch C & Pluen A, EU Biophys J. 2007)

Future Research

I am now concentrating on the physical biology of veterinary or human diseases.

School of Veterinary Medicine and Science

University of Nottingham
Sutton Bonington Campus
Leicestershire, LE12 5RD

telephone: +44 (0)115 951 6116
fax: +44 (0)115 951 6415
email: veterinary-enquiries@nottingham.ac.uk