Pharmaceutical and
Biopharmaceutical
INNOVATION HUB
Biomembrane
Research
Who we are?
Related Academics
The University of Leeds has internationally leading research programmes in understanding and characterising biological membranes
and their proteins. We represent 16 research groups that span 5 scientific schools from the biological and biomedical sciences to the
physical sciences.
Leeds Institute of Genetics, Health & Therapeutics:
• G Protein-coupled receptors
• Molecular Pharmacology
Prof Chris Peers
Prof John Colyer
What do we have to offer?
By combining our expertise we aim to offer, in a single location, an unparalleled, diverse spectrum of expertise capable of addressing a
wide array of industry’s challenges related to handling and characterising biological membranes and their proteins. We are capable of
providing a multi-strategy approach (physical, chemical and biological), taking advantage of an established interdisciplinary ethos at Leeds.
This is illustrated by the Astbury Centre for Structural Molecular Biology which brings together more than 250 researchers, at the interface
between physical and biological sciences, with projects valued over £55M. The majority of academics linked to biomembrane research at
Leeds are members of the Astbury centre. Other centres within the university follow a similar interdisciplinary philosophy.
What are we looking for?
We are seeking to enhance our engagement with industry on problems related to the characterisation of biomembranes and membrane
proteins. We plan to share our expertise through consultancy and collaborative research projects of mutual interest and benefit. We also
aim to hold focussed conference-style workshops addressing current challenges faced by industry related to working with biomembranes.
We are currently seeking feedback from leading industrial stakeholders with strong interests in
biomembranes, about how our capabilities and expertise map onto the key challenges they face. This
will help us refine and focus our offerings.
Examples of challenges we may help to address include:
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Novel reconstitution systems for membrane proteins (for assaying, structural studies, etc.);
Understanding drug/particle – biomembrane interactions;
Expression, purification and functional analysis of membrane proteins;
Investigation of the effects of drugs on membranes and membrane proteins;
Novel biosensors, e.g. for toxicology.
Brief summary of biomembrane expertise and facilities:
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Membrane Proteins:
- Prokaryotic/eukaryotic membrane proteins;
- GPCRs; Ion Channels; Transport proteins;
- Sensory kinase receptors; Gasotransmitters;
- ATPase motor proteins;
- Respiratory enzymes (electron transport).
Model membrane systems:
- Solid-supported/surface-tethered membranes;
- Giant vesicles, liposomes, lipopolymersomes;
- Nanodiscs;
- Lipid monolayers on Hg.
Biological Techniques:
- Cloning, expression, purification, solubilisation & reconstitution of membrane proteins;
- Bacterial, yeast and baculovirus/insect cell expression systems;
- Protein functional assays;
- Mutagenesis;
- Aptamers and artificial binding proteins against
membrane proteins;
- Molecular pharmacology.
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Physical Techniques:
- Optical microscopies;
- Electron microscopy (including cryogenic);
- Spectroscopies (fluorescence, absorption, FT-IR, DLS, DELSA, etc.);
- AFM and other surface analytical methods
(e.g. neutron reflectivity, QCM-D, SPR);
- Electrochemistry/electrophysiology;
- Crystallisation/X-ray crystallography; NMR;
- Novel technique development to probe properties of membranes and their proteins;
- Membrane protein reconstitution and crystallization;
- Surface arrays for high throughput screening.
Theory & Computer Simulation:
- Membrane phase behaviour;
- Mechanics and dynamics;
- Protein – membrane interactions; Pore formation;
- Skin lipids.
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Dr. Kate Langton
Dr. Paul Beales
Innovation Manager
Pharmaceutical & Biopharmaceutical Hub
University of Leeds
E: [email protected]
T: +44 (0) 113-343-6503
Senior Research Fellow
School of Chemistry
University of Leeds
E: [email protected]
T: +44 (0) 113-343-9101
• Membrane protein structure-activity relationships (SERCA, phospholamban)
• Antibodies to key features on membrane proteins
• Regulation of degradation of membrane proteins
School of Chemistry:
Prof Andrew Nelson
School of Biomedical Sciences:
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Prof Peter Henderson
Dr Paul Beales
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Bioenergetics, antibiotic action and enzyme kinetics
Discovered the mechanisms of action of membrane-active antibiotics and novel methods of measuring kinetics of enzyme inhibition.
Energetics of sugar transport into bacteria, characterising proton-linked mechanisms
of transport.
Discovered the similarities between transport proteins in microbes and man.
He and his group have expressed over 70 membrane transport and receptor proteins from 14 species of bacteria, purified over half of them, and are currently elucidating their structures by Xray crystallography and NMR, culminating in the determination of the structure and probable molecular mechanism of a sodium hydantoin transport protein in a collaboration with Professor So Iwata [Science (2008) 322. 709-713; Science (2010) 328, 470-473].
Over 160 research publications and has been member of editorial boards of six journals.
During 2003-2008, he was Scientific Director of the European Membrane Protein
consortium, EMeP, and in 2008-2012 Coordinator of the European Drug Initiative
for Channels and Transporters, EDICT.
Prof Stephen Baldwin
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High throughput construction of expression vectors for expression of membrane
transporters and channels from prokaryotes and eukaryotes
The production of these proteins using bacterial, yeast and baculovirus/insect cell
expression systems
Purification, reconstitution and characterisation of membrane proteins using
functional assays and biophysical approaches (circular dichroism, infrared
spectroscopy, 3-D crystallography etc.).
Molecular modelling of membrane proteins.
Dr Lars Jeuken
• Biosensing: Detection of protein binding to lipid bilayers or transmembrane-protein
(in the lipid bilayer) using methods outlines below.
• Biosensing: Detection of transport activity and ion channel (ligand-gated ion channels) activity of membrane proteins using label-less methods (NaNion SURFE2R technology).
• Creation of solid-supported membranes (also known as solid-supported bilayer lipid
membranes; sBLM) containing transmembrane protein (monotopic and polytopic) on glass and its analysis with
- Quartz-crystal microbalance with Dissipation
- Fluorescent microscopy (Fluorescent recovery after photobleaching)
- (together with Khizar Sheikh/Simon Connell) Atomic-force microscopy
• Creation of tethered bilayer lipid membranes (tBLM) on ultra-smooth gold containing transmembrane proteins (monotopic and polytopic) and its analysis with
- Impedance spectroscopy
- Quartz-crystal microbalance with Dissipation
• Respiratory membrane enzymes; biological electron transport
Dr Stephen Muench
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The structure, mechanism and regulation of large protein complexes, in particular
membrane proteins.
Combination of Electron microscopy, X-ray crystallography, kinetics, molecular
dynamic simulations and a range of biochemical techniques.
The development of time-resolved cryo-EM, to trap protein complexes in
conformational states, providing insights into their mechanism.
Currently developing techniques to study membrane proteins in situ by Cryo
Electron Microscopy.
Dr Jonathan Lippiat
• Research topics: ion channels and transporters, inherited disorders, pharmacology,
structure-function.
• Techniques: electrophysiology, fluorescence imaging, assay development, gene
cloning and expression.
Prof Asipu Sivaprasadarao
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For further information, please contact:
Ion channels (sodium, calcium, potassium) – I study function (patch-clamp), regulation (signal transduction pathways, trafficking etc) and structure (mutagenesis)
Ion selective fluorescent dyes – primarily for calcium, but also for nitric oxide, peroxynitrite. I study calcium homeostasis routinely, which involves calcium movement across plasma and intracellular membranes
Gasotransmitters – their biological activity and roles in diseases. I am particularly interested in the regulation of ion channels by oxygen, carbon monoxide, hydrogen sulphide and nitric oxide.
Dr Dan Donnelly
Membrane protein expression and purification (Ion channels)
Ion channels - structure-function and cell biology
Cell signalling in relation to cell death
Electrophysiology
Dr Lin-Hua Jiang
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Structure, function, disease and therapeutics of P2X and TRPM ion channels
Profiling ion channel expression, using quantitative PCR, Western blotting,
immunofluorescent confocal imaging, and biotin-labelling assays
Elucidating ion channel structure-function relationships, using directed
mutagenesis, structural modelling, and patch-clamp recording (structural modelling
in collaboration with Prof Baldwin)
Characterising ion channel activity and pharmacology, using single cell imaging and
patch-clamp recording
Investigating role of ion channels in diseases, using rodent disease models
Developing ion channels antagonists for therapeutics, by high throughput screening
and iterative and structure-activity in collaboration with Dr R Foster in Chemistry
electrochemistry of supported phospholipid layers
application to sensing assessment of pharmaceutical biomembrane activity
importance of the biomembrane in ecotoxicology
• Investigating unsupported membranes in giant unilamellar vesicle models at the single vesicle level by optical microscopy techniques (phase contrast, epifluorescence, confocal, multiphoton):
- phase separation (e.g. lipid rafts)
- Interaction of proteins, peptides (e.g. Antimicrobial Peptides; AMPs), polymers and nanoparticles with lipid membranes
- dynamic morphology changes
- permeability of molecules and macromolecules
- lipid mobility (Fluorescence Recovery After Photobleaching; FRAP)
- environment-sensitive fluorophores (e.g. Laurdan)
• Dynamic light scattering, electrophoretic light scattering, UV/vis and fluorescence
spectroscopies
• Hybrid lipid – block copolymer vesicles
• Protein-stabilised lipid nanodiscs / bicelles
• Bionanotechnology (DNA-lipid conjugates, compartmentalisation, nanomedicine)
School of Molecular and Cellular Biology
Prof Mike McPherson
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The use of semi high throughput approaches for the cloning of membrane protein
encoding genes.
Protein engineering and directed evolution.
Screening of proprietary artificial binding protein libraries against membrane proteins for applications such as:
- co-crystallization chaperones;
- diagnostic purposes;
- locking membrane proteins in specific functional conformations;
- assisting small molecule drug design by identifying potential druggable sites
- blocking protein-protein interactions
School of Physics:
Prof Peter Olmsted
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Theory of phase behaviour, mechanics, and dynamics of membranes. This includes
continuum level generalised elasticity and hydrodynamics, as well as an interest in the
details at a leaflet level, and the effects of different compositions.
Simulations of bilayers. Interest in protein-membrane interactions and the relation to
pore formation and the interaction with different compositions.
Stratum corneum (skin) lipid bilayers.
Currently collaborating with Dr. S Connell on an EPSRC Programme grant to study the
intertwined roles of curvature, asymmetry, and patterning on, ultimately, collective
membrane behaviour.
Prof Stephen Evans
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The formation and characterisation of tethered lipid membranes and solid supported lipid membranes:
- to create membrane arrays for diagnostic screening or biosensing.
- for in situ membrane protein purification, protein separation.
Experience in a wide range of analystical techniques for studying membranes
including neutron reflectivity, Fourier transform, Infrared spectroscopy, quartz crystal
microbalance, surface plasmon resonance, impedance spectroscopy and AFM.
The development of GUVs for diagnostic screening and synthetic biology:
- actin membrane interactions.
Therapeutic delivery using:
- SUVs and lipid coated oil nano particles for drug delivery.
- microbubbles as a delivery vehicle for theragnostic applications.
Dr Simon Connell
• Imaging of supported membranes at nanometre resolution via AFM, simultaneous
with fluorescence microscopy under aqueous conditions.
• Ability to investigate structure and dynamics over wide length and temporal scales. Temperature range 0 -80 degrees.
• Quantitative mechanical characterisation of membranes using the latest AFM modes available.
• Development of new techniques or instrumentation to solve particular problems.
• Spatial mapping of bilayer surface charge.
• Complex phase behaviour in model phospholipid membranes and cell membranes. Two phase and three phase co-existence. Dynamic behaviour within a single phase.
• The action of detergents, peptides, oligomers, fibrils and transmembrane proteins on membrane phase and overall integrity.
• Ceramide/Fatty acid Stratum Corneum (skin) lipids – characterisation of structure, mechanical and thermal properties, and the effect of additives. Interaction of skin lipids with supporting substrate as a function of hydrophobic/hyrdrophillic balance.
• Imaging and discrimination of asymmetric bilayers.
• In situ growth of actin filaments on membrane.
www.pharmahub.leeds.ac.uk
Leeds, United Kingdom
LS2 9JT
Tel. 0113 243 1751
www.leeds.ac.uk