The Aston Centre for Membrane Protein and Lipid Research (AMPL) is a collaborative team of principal investigators in biochemistry, molecular modelling, pharmacology, protein/lipid chemistry, cell biology and polymer science. We study the structure and function of membrane proteins and associated lipids, using interdisciplinary approaches and our novel technologies. Our research feeds into the overarching College of Health and Life Sciences specialism of cellular and molecular biomedicine.
Membrane proteins are the subject of intense study in industry and academia because they underpin fundamental biological processes and are therefore critical targets for the development of new therapeutics. All of the current top-ten-selling pharmaceutical drugs worldwide target a membrane protein, while understanding membrane proteins is an essential step in discovering the medicines of tomorrow.
Membrane proteins are also biomarkers for health and disease and regular candidates for genetic modification to improve livestock, crops and to control pests. However, membrane proteins are challenging to work with, as they are neither naturally abundant nor stable, meaning very few laboratories have the expertise or capacity to consistently synthesize and purify the large quantities of high-quality protein required to meet these needs.
Our activities to date show our ability and expertise in meeting these challenges, creating synergistic projects over a range of scales with demonstrable real-world impact.
Our research has been funded by a variety of sources including:
- Biotechnology and Biological Sciences Research Council (BBSRC)
- Engineering and Physical Sciences Research Council (EPSRC)
- The European Commission
- The WellcomeTrust
- IB Catalyst.
We are also part of MemTrain, a five year COFUND project working with industrial partners across Europe to train the next generation of researchers (ESRs) who are primed to work on developing a new understanding of how to harness the full potential of cell membranes. In addition to a three year ERA CoBioTech project MeMBrane led by Dr Alan Goddard.
We have significant expertise in working with industrial partners (recently including Peak Proteins, Sygnature Discovery, Janssen, Calixar, F2G and UCB) to understand their requirements for specific applications.
We are a collaborative team of scientists using techniques from biochemistry, molecular modelling, pharmacology, protein/lipid chemistry, cell biology and polymer science to answer important questions about membrane protein-lipid interactions using interdisciplinary approaches and our novel technologies.
Centre Director: Professor Roslyn Bill
Roslyn is Aston’s 50th Anniversary Professor of Biotechnology within the School of Biosciences and Associate Dean (Research) for the College of Health and Life Sciences. She develops yeast to synthesize membrane proteins for further study with a particular focus on aquaporins, tetraspanins and G protein-coupled receptors.
- Dr Zita Balklava
- Professor Andrew Devitt
- Dr Alan Goddard
- Professor David Poyner
- Dr Alice Rothnie
- Professor Corinne Spickett
- Dr John Simms
Researchers in AMPL make use of the following facilities, which are also open to external collaboration.
- ARCHA Advanced Imaging Facility
Microscopy is a fundamental technique for cell-based investigations as it allows detailed sample visualisation. The ARCHA Advanced Imaging Facility currently provides a large number of research groups, including the Bioscience Research Group with access to state-of-the-art microscopy equipment.
- Mass Spectrometry and Lipidomics Laboratory
Home to three mass spectrometers, all of which can be interfaced to both analytical and nanoflow liquid chromatography systems, this laboratory is open to collaborators and trained research users.
- Membrane protein-lipid interactions
Our work has contributed to the development of technological, methodological and analytical approaches that are essential for producing and studying membrane proteins. Significantly, we have demonstrated that traditional methods of membrane protein expression and purification can be optimised and that, in some cases, the lipid environment is of such fundamental importance to membrane protein function that it is essential to tailor bespoke expression and purification approaches.
We have developed and optimised a range of technologies which, in essence, form in-house ‘trade secrets’ including:
- A panel of cell and organismal expression systems, both prokaryotic and eukaryotic.
- Solubilisation methodologies including traditional and novel detergents as well as commercially-available and in-house polymer-based systems.
- Purification strategies based on traditional tagging systems but also antibody and ligand-mediated approaches.
- Activity assays including ligand binding, transport and enzymatic analyses.
- Lipidomics via chromatographic and mass spectroscopic approaches.
In addition to our fundamental underpinning research, we have significant expertise in working with industrial partners (recently including Peak Proteins, Sygnature Discovery, Janssen, Calixar, F2G and UCB) to understand their requirements for specific applications. These include defining desirable protein and coding sequences, purity, lipid environment, concentration, activity and stability.
- Industrial biotechnology
The global economy has an unsustainable dependence on fossil raw material. Concerns about environmental sustainability are becoming more acute; thus, alternatives to traditional, fossil-fuel based chemical production are urgently required.
Cell factories, which use microorganisms to produce materials from renewable biomass, are an attractive alternative, and an increasing number of platform chemicals are being produced at industrial scale using engineered microorganisms. These are expected to have a transformative impact in industrial biotechnology, but, first, we must meet the challenges of designing and optimizing high-yielding cell factory strains that can produce commercially viable amounts of product. One reason for poor product output is that the production conditions are ultimately toxic to the producing cells. In addition to damage to intracellular components such as enzymes, the lipid cell membrane and associated proteins are vulnerable to biomolecules e.g. ethanol and propionate, as well as to physical parameters during production such as osmotic stress, pH, and temperature.
Our focus is to tune the lipid and protein content of membranes so cells become more resistant to stresses brought about by toxicity. Additionally, expression of efficient membrane transporters to export 'toxic' products can mitigate intracellular damage. These approaches will ultimately enable production of higher concentrations of the desired molecules or cells making the bioprocesses more efficient, increasing product yield, reducing cost, and helping to drive the move away from fossil-based raw materials.