The HAMLET molecular species with anticancer properties

Summary

We are interested to determine how the anti-cancer properties of this family of molecules can be translated into cancer treatment. We believe there may be a delivery system which negates the flaws of these species as they present natively.

Supervisor(s)

Dr W Bret Church

Research Location

Sydney Pharmacy School

Program Type

Masters/PHD

Synopsis

The HAMLET family of compounds (human alpha-lactalbumin made lethal to tumours) is composed of the alpha-lactalbumin protein "carrier" and oleic acid. They show broad spectrum anti-cancer activity in vitro. We have performed structural studies on the BAMLET compounds (the bovine equivalents with similar properties to the human versions) as well as a beta-lactoglobulin analogue. Our work indicates that the majority of the protein is located on the periphery of the BAMLET and the protein component does not completely fill the centre. The current evidence is that the oleic acid is the component with the anti-cancer activity, and we are carrying out further experiments to provide further specific information on the oleic acid, in addition to the protein component. These scattering results support a structural model beginning to explain the delivery of the oleic acid of the broad spectrum anti-cancer activity of the BAMLET family of compounds - the protein carrier is able solubilise a large number of oleic acid molecules by carrying them internally in an oversized protein. This model is consistent with the absence of specific cancer cell binding sites in the action of BAMLET on cells in vitro, suggesting that if a suitable approach to delivering HAMLET and HAMLET-like molecules in the in vivo situation can be developed, cancers against which the therapy is directed would not be able to evolve resistance to BAMLET treatment by point mutations for instance. We are continuing our studies pursuing the specifics of these anti-cancer species, as well as studies to find delivery systems which preserve the salient features of HAMLET-like molecules with the potential to be effective anti-cancer treatments. This work is with our collaborators, Drs Anthony Duff and Robert Knott at ANSTO, as well as Anders Hakansson, University of Buffalo, in the U.S.A.

Additional Information

Techniques with the potential to be used are enzyme and cell-based assays, molecular biology, bioinformatics, microscopies, X-ray crystallography, small angle X-ray scattering, small angle neutron scattering, molecular modeling; aspects may be suitable as Honours projects.

Want to find out more?

Contact us to find out what’s involved in applying for a PhD. Domestic students and International students

Contact Research Expert to find out more about participating in this opportunity.

Browse for other opportunities within the Sydney Pharmacy School .

Keywords

Bioinformatics, sequence analysis, Crystallisation, protein structure, drug delivery, Proteins, lipids, drug design, Cancer, HAMLET, BAMLET, lactoglobulin, oleic acid

Opportunity ID

The opportunity ID for this research opportunity is: 1881

Other opportunities with Dr W Bret Church