Prof Stephen Evans

Stephen Evans is Professor of Molecular and Nanoscale Physics in the School of Physics and Astronomy. He obtained his B.Sc. in Physics from the University of London (QMC) in 1984 and his PhD in Molecular Physics from the University of Lancaster in 1988. After a post-doctoral fellowship at Imperial College, University of London, he became a visiting scientist in the Molecular and Optical Electronic Research Laboratory, Eastman Kodak, Rochester, New York. He joined the academic staff of the University of Leeds in 1991, became a Reader in 2001, and was appointed as Professor in Molecular Physics and Nanoscale Physics in 2002. He was Chairman of the School of Physics & Astronomy between 2004-2007 and currently heads the Molecular and Nanoscale Physics group.

Research Areas: Supported lipid membranes; Bio-templated nanowires and Nanostructured materials.

Areas of Research:

Supported Lipid Membranes, Liposomes and Microbubbles.

Solid supported and tethered lipid membranes can be formed on a variety of surfaces to produce a biomimetic membrane that has the fluidity and permeability close to that of their native counterpart. As such, they provide an ideal platform for the study of membrane proteins, processes that occur at membrane surfaces, and importantly allow the application of a wide range of analytical techniques including; Neutron and IR reflectivity, AFM, SPR, SPFS and QCMD for their study.

Bacterial cell wall growth and antibiotic interactions.

Our interest here is in “reconstructing” the peptidoglycan (PG) bacterial cell wall through the step-by-step increase in the molecular complexity of our membrane systems. This “deconstruction” of the synthetic pathway for PG formation will allow us to address some basic questions regarding the process of PG formation, modes of antibiotic action, and allow us to create screening platform for novel antibiotics. The work has involved close collaboration with Prof. T. Bugg, in Warwick, and the UK BACWAN Network.

Ponticulin, Actin Scaffolds and Cortices.

Ponticulin is one of the few membrane proteins known to bind actin directly and is consequently of interest to us in creating hierarchically complex membrane structures. Our initial studies have centered on the expression and purification of Ponticulin, a type VI membrane protein consisting of a transmembrane domain as well as a glycosyl-phosphatidylinositol anchor. Through incorporation into supported bilayers we have been able to investigate the interaction between ponticulin and G- / F- actin using AFM and fluorescence microscopy. We are currently undertaking preliminary studies into the formation of actin cortices in giant liposomes (GUVs) with the hope of building, from the “bottom-up”, structures with dynamic 3D internal organization. Additionally, we are also investigating the role of the GPI anchor in localizing ponticulin to microdomains in lipid mixtures.

In collaboration with Prof G. Banting (Bristol) we hope to extend this assemble a synthetic functional 'cytoskeleton/membrane' module from purified components. This module will have the most important basic features of a natural cytoskeleton. Its composition will be precisely controlled and its constituents will be designed, emphasizing the truly synthetic nature of this approach. Not only will this lead to a deeper understanding of the biological principles governing the role of membrane proteins and the actin cytoskeleton in the construction of cell architectures but it will also permit us to design and create “de novo” organelles /cells.

Microbubbles for Therapeutic Delivery.

We are developing microbubbles (MBs) and ultrasound (US) technologies to aid the treatment of colorectal cancer (CRC), the third most common cancer in the UK. So-called “third generation” MBs will not only allow functional imaging with greatly enhanced sensitivity and specificity but will also carry therapeutic payloads for treatment or gene therapy. These will be released at the target site and their effect further enhanced by sonoporation. Although the focus of our proposal is therapeutic delivery for cancer treatment, the basic technology development is generic and will be equally applicable to other conditions, e.g. cardiovascular and musculoskeletal disease. Our project addresses several key issues central for the successful development of these 3rd Generation MBs; i) “on-demand” production of uniform, multifunctional MBs using microfluidics, ii) investigation of MBs with novel, lipid and proteo lipid, coatings), iii) bio-functionalisation of MBs for payload attachment and targeting, iv) development of new coding schemes for US excitation to expedite MB destruction and sonoporation-aided delivery and finally, iv) pre-clinical evaluation of the MBs developed above for targeted therapy of CRC (and metastases) using a combination of in vitro and in vivo models. This multidisciplinary project is carried our in collaboration with Coletta (LIMM) and Freear (Electronic Engineering), at Leeds.Self-Assembly at Surfaces

Switchable Nanostructured Surfaces for Cell Biologists.

This project is for the development of Switchable Nanostructured Surfaces. These are molecularly well-defined surfaces, which in a highly controlled way can dynamically present biological regulatory signals and stimuli to a cell with nanometre localised resolution. We are exploiting the principles of self-assembly, molecular shape change and nanofabrication to engineer the tunable biological nanoscale features on macroscopic surface materials. In order to achieve its aim, this project has three central objectives: i) Development of stimulus-responsive molecular systems for real-time and reversible control of biomolecule activity on large scale surfaces, ii) Development of a nanopatterning methodology that will allow immobilisation of multiple biologically differing stimuli systems at well-defined and nanoscale locations with a high degree of selectivity, iii) Test and exploit smart switchable biological nanostructured to investigate stimulus-activated calcium concentration [Ca2+]i signalling and cell responses in sperm and how these relate to “cell quality”. This work is in collaboration with Mendes (PI), Publicover and Jackson Browne (Birmingham).

Spin Crossover on the Nanoscale.

Spin-crossover (SCO) occurs due to the rearrangement of the electrons in an atom in response to a change in temperature. This is common in some types of transition metal compound, being particularly prevalent in iron chemistry. While the molecules in a material undergo spin-crossover individually, it leads to large changes in their size and shape, which is propagated through the material in the solid state. In collaboration with Halcrow (Chemistry, Leeds) we are using STM, XPS and FTIR to study spin-crossover in two-dimensional lattices, formed from monolayers of functional iron centres bonded to a gold surface. Under these conditions we hope to measure the propagation of the transition in the monolayer as a whole, or in close-up by individually monitoring small clusters of molecules. By measuring the transition at different positions of the layer, we can map how the transition proceeds at the atomic level. It has recently been proposed, that a spin-crossover event is initiated at flaws in the lattice structure, before propagating into the bulk. We hope to be able to observe that experimentally. Further, we are hoping to develop new types of switchable surfactants, that self-assemble into nanostructures in solution. Our aim is to make weakly associating hollow spheres or tubes that reversibly change their size or shape as their molecules undergo spin-crossover. Structures like this, that reversibly change their aggregation at different temperatures or pHs, can be made to release a chemical payload following their structural transformation.