The groups focus is on understanding structure function relationships of amphiphilic bioactive molecules and the design of new biomaterials. The group is multidisciplinary and draws on a range of specialisms including, biology, (cell biology and microbiology), chemistry (biochemistry, synthetic chemistry), physics (biophysics, nano physics) and computational modelling to:
- Investigate the mode of action of helical peptides and other bioactive amphiphilic molecules and to identify their molecular target(s)
- Undertake structure-activity studies to improve the antimicrobial activity and oncolytic properties of amphiphilic, membrane interactive compounds
- Develop computational methods for the identification and assessment of key functional characteristics of amphiphilic molecules with medical applications
Interest in amphiphilic molecules.
A major problem facing medical science is the increasing occurrence of resistance to antimicrobial and anticancer agents, which has led to the need for new lead compounds in strategies of drug design. Such agents need to be able to target specific cells and disrupt their function hence efficacy can be reduced by either poor selectivity or poor activity at the target site.
A key feature of interest is the membrane surrounding the cell since this may be the target site for any new agent or if not it will need to be traversed for the agent to reach the cell interior. These membranes form a phospholipid barrier around the cell and exhibit a hydrophobic interior and hydrophilic exterior. The function of many biologically active molecules is therefore dependent upon their own amphiphilic structure either because the membrane is the site of action or because it is their physicochemical characteristics that will determine their translocation across the bilayer and their subsequent compartmentalization within the cell. Currently, the main focus for our group’s interest is therefore to investigate the structure function relationships underpinning the membrane interactions of known biologically active molecules and the role of amphiphilicity in the activity of such biomolecules.
Work is currently focused in two areas. The first is investigation into the properties of membrane interactive peptides such as antimicrobial peptides – a number of which have also been seen to exhibit anticancer properties. The second involves the creation of synthetic amphiphilic molecules which may have potential in the targeting and destruction of bacterial cells or tumour cells. Investigations of this kind can not only give insight into the functionality of the molecules themselves but as we gain understanding of how they cause lysis we can apply this knowledge to aid our understanding of a wide range of key biological processes that require on-going membrane fusion and lysis events.
- Dennison, S.R., & Phoenix, D.A. (2011), Influence of C-terminal amidation on efficacy of modelin 5, Biochemistry, 50, 1514-1523.
- Harris, F, Dennison, SR and Phoenix D. A. (2011) On the selectivity and efficacy of defence peptides with respect to cancer cells, Medical Research Reviews, In Press (DOI 10.1002/med.20252)
- Harris, F, Dennison, SR and Phoenix D. A. (2011) Antimicrobial peptides from eukaryotic organisms and their mechanisms of action, Current Chemical Biology, 5, 142-153
- Ahmed, M. Byrne, A. J., McLaughlin, J., Ehlissi, A., Phoenix DA, Ahmed, W. (2011) Vibrational and AFM Studies of adsorption of glycine on DLC and silicon doped DLC. J Materials Science, 47, 1729-1736.
- Dennison, S.R., & Phoenix, D.A. (2011), Effect of cholesterol on modelin efficacy, Biochemistry, 50, 10898-10909
- Harris F, Dennison, S.R., & Phoenix, D.A. (2012), Aberrant action of amyloidogenic host defense peptides: a new paradigm to investigate neurodegenerative disorders? FASEB J., 26, 1776-1781
- Dennison, S.R., Akbar, Z, Phoenix, D.A. Snape, T (2012), Interactions between suitably functionalised conformationally distinct benzanilide and phospholipid monolayers. Soft Matter, 8, 3258-3264
- Dennison, S. R., Morton, L. G. H., and Phoenix, D. A., (2012), Effect of amidation on the antimicrobial peptide aurein 2.5 from Australian southern bell frogs. Prot. Pept. Lett., 19, 586-591.
- Dennison, S. R., Morton, L. G. H and Phoenix, D. A., (2012), Role of molecular architecture on the relative efficacy of aurein 2.5 and modelin 5. Biochem. Biophys. Acta, 1818, 2094-2102
- Hamblin D. And Phoenix D. A., (2012), A model for managing data assurance in higher education. J Higher Education Policy and Management, 34, 421-435
- Elhissi, A., Giebultowicz, J., Stec, A., Wroczynski, P., Ahmed, W., Alhnan, A., Phoenix, D. A., Taylor, K. M., (2012), Nebulization of ultradeformable liposomes: The influence of aerosolization mechanism and formulation excipients. Int. J. Pharmaceutics,436, 519-526
- Dennison, S.R, Phoenix, D.A. Snape, T.,(2012) Thermodynamic interactions of a cis and trans benzanilide with E. coli bacterial membranes. Eur. J Biophys., In press
- Dennison, S.R, Phoenix, A., and Phoenix, D.A., (2012) Effect of salt on the interaction of Hal18 with lipid membranes. Eur. J Biophys., 41, 769-776.
- Mura, M., Dennison, S., Zvelindovsky, AV and Phoenix DA, (2013), Aurein 2.3 functionality is supported by oblique orientated a-helical formation. Biochem. Biophys. Acta. 1828, 586-594
- Abdelbary Elhissi, Kanar Hidayat, David A. Phoenix,Enosh Mwesigwa, StJohn Crean, Waqar Ahmed,Ahmed Faheem, Kevin M.G. Taylor, (2012), Air-Jet and Vibrating-Mesh Nebulization of Niosomes Generated Using a Particulate-Based Proniosome Technology. Int. J.Pharmaceutics In press.
- Oliveira, LMA, Gomes, RA, Yang, D, Dennison, SR, Familia, C., Lages, A., Coelho, AV, Murphy RM, Phoenix, DA, Quintas, A., (2012) Insights into the molecular mechanism of protein native-like aggregation upon glycation. Biochem. Biophys. Acta. In press
- Khalid, N. R., Ahmed, E., Ikram, M., Ahmed, M., Jackson, M. J., Phoenix, D. A., Elhissi, A., and Ahmed, W., (2012), Effects of calcination on structural and photocatalyltic properties of TiO2 nano-powders via TiCL4 hydrolysis. J. Mat. Eng. & Performance. In press.
The following books and edited collections are available:
- Membrane Protein Insertion (Ed. D. A. Phoenix) 1995, Biochem. Soc. Trans. 23, 959-991.
- Protein Targeting and Translocation – XII Research Monograph of the Biochemical Society. (Ed. D. A. Phoenix) 1998, Portland Press, pp300. This was reprinted with permission in the US by Princeton University Press as Protein Targeting and Translocation (Ed D. A. Phoenix).
- Structure – Function Relationships of Amphiphilic Alpha Helical Peptides (Eds D. A. Phoenix & F Harris) 2006, Volume 7, Current Protein and Peptide Science, Bentham Publishers.
- Antimicrobial Peptides (Eds S Dennison, D. A. Phoenix), 2010, Protein Peptide Letters, Bentham Publishers, Volume 17 issue 11
- Antimicrobial Peptides, Phoenix, D. A., Dennison, S & Harris F, 2013, Wiley Publishers,
9 February 2013Lab featured in Bachem PEPTalk
Our lab was recently featured in Bachem PEPtalk. This is a regular newsletter produced by Bachem – a major international biochemical technology company.
- Prof David Phoenix
- Dr Sarah Dennison
- Dr Timothy Snape
- Dr Yuhua Zhou
- Dr Jianping Wang
Analysis and prediction of peptides and proteins propensity for amyloidogenicity