... understanding life in molecular detail

Dr Paul Beales

Lipid membranes, Directed assembly, Nanomedicine, Synthetic Biology


Much of our research is inspired by the functional roles of biological membranes in regulating the spatial compartmentalisation and transport of chemical information within cells, tissues and organisms. We aim to combine natural biomolecules with synthetic polymers and particles to engineer novel materials as well as to use physical science approaches to improve our understanding of the structure and function of membranes in biology. These goals lead towards applications in drug delivery, toxicology and nanoreactors, while moving us closer towards realising the bottom-up design of synthetic biological cells in the lab.

Current major projects include:
  • Biophysics of interactions between nanomaterials and lipid membranes.
  • Biomimetic self-assembly of membrane-based materials.
  • Soft materials for encapsulation and delivery of bioactive compounds.
  • Bottom up assembly of minimal model cells.

Biophysics of interactions between nanomaterials and lipid bilayer membranes.

Advances in synthetic nanoparticles and polymers mean that they are finding ever more industrial applications and may even find roles within in vivo clinical applications for diagnostics and therapeutic delivery. In order to optimise the biomedical properties of nanomaterials or minimise their health risks in consumer products, it is essential to understand how they interact with and perturb biological membranes. We use giant lipid vesicles (GUVs) as our primary model membrane system to investigate these interactions at the single vesicle level. Our aim is to develop a model framework to understand nanoparticle – biomembrane interactions that will allow a priori design of nanoparticles with optimised interaction with biomembranes, whether that be minimal interaction for reduced toxicity or optimised membrane translocation for biomedical therapies.

We also use biophysical analysis of GUV model membranes to investigate their interactions with relevant biomolecules. Examples of recent interest include understanding the interaction of the peripheral protein cytochrome c with model mitochondrial membranes and understanding the role of lipid composition in the membrane-perturbing action of antimicrobial peptides.

Biomimetic self-assembly of membrane-based materials.

We aim to make novel functional materials by making hybrid composites of natural biomolecules and synthetic polymers or particles. These include directing the assembly of multicompartmental vesicle clusters using DNA-lipid conjugates as smart, molecular glue, creating supramolecular polymer fibres from lipid bilayer nanodiscs assembled into periodic linear arrays through DNA-mediated assembly, and robust, hybrid vesicles formed from natural lipids and synthetic block copolymers. These bioinspired materials have applications across many technological disciplines, including nanomedicine, nanoreactors, pharmaceutical assaying and synthetic biological devices.

Soft materials for encapsulation and delivery of therapeutic and diagnostic agents.

We are developing a number of self-assembled nanomaterials for application in nanomedicine. Our philosophy is the design materials composed of biomolecular and biodegradable composites in order to minimise potential toxicity of the therapeutic packaging material within these formulations. We are interested in taking advantage of how cells traffic nanoscale materials dependent on their size, shape and mechanical properties, as well as designing multicompartmental architectures for applications in combination therapies or theranostic treatments. We currently have collaborations in the clinical areas of bladder cancer and colonic diseases.

 

Bottom up assembly of minimal model cells.

The controlled compartmentalisation and transport of chemical information is central to the function of living organisms. We are applying our expertise in understanding and controlling reconstituted membrane-based systems to develop structures with encapsulated synthetic cytoplasms. We are interested in controlling natural and synthetic routes to signalling across lipid membranes between distinct chemical compartments. This includes the design of systems with multiple aqueous compartments (e.g. synthetic organelles). Our goal is to create new functional biologically-based devices and materials while, along the way, discovering new insights into the operation of biological systems.

Detailed research programme                  Close ▲
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Senior Translational Research Fellow
MPhys (Edinburgh) PhD (Edinburgh)

PhD Student (Univesity of Edinburgh) 2001-2005
Postdoc Research Associate (Princeton Uni) 2005-2008
Postdoc Research Associate (Yale University) 2008-2010

Chemistry 1.13
School of Chemistry
0113 343 9101
p.a.beales@leeds.ac.uk

http://www.chem.leeds.ac.uk/paul-beales

Selected Publications

  1. Bergstrom CL; Beales PA; Yang L; Vanderlick TK; Groves JT. Cytochrome c causes pore formation in cardiolipin-containing membranes. Proc. Natl. Acad. Sci. USA 110 (16), 6269 - 6274, 2013

  2. Beales PA; Geerts N; Inampudi KK; Shigematsu H; Wilson CJ; Vanderlick TK. Reversible assembly of stacked membrane nanodiscs with reduced dimensionality and variable periodicity. J. Am. Chem. Soc. 135 (9), 3335–3338, 2013

  3. Bueno Leite N., Aufderhorst-Roberts A., Palma M.S., Connell S.D., Ruggiero Neto J. and Beales P.A.; PE and PS Lipids Synergistically Enhance Membrane Poration by a Peptide with Anticancer Properties. Biophys. J. 109 (5), 936 - 947 (2015)

  4. Beales P.A., Ciani B. and Cleasby A.; Nature's lessons in design: nanomachines to scaffold, remodel and shape membrane compartments. Phys. Chem. Chem. Phys. 17, 15489 - 15507 (2015)