Development of host defence peptides as therapeutics to treat drug-resistant metastatic melanoma
Acquired drug resistance is a serious problem for the treatment of metastatic melanoma. Melanoma is the most dangerous form of skin cancer due to its metastatic potential and late stages of the disease are treated with radiotherapy, or conventional chemotherapy. These treatments have low specificity, high toxicity for healthy cells, and induce drug-resistance.
This project will be focused in developing anti-melanoma therapies less likely to induce drug-resistance by using stable host defense peptides. In recent years, we have identified host defence peptides active against metastatic melanoma cells, and not toxic towards tested healthy cells. In addition, these peptides are resistant to proteases, can cross cell membranes, and are very amenable to structural modifications. Our preliminary studies showed that these peptides are also active towards metastatic melanoma cells that have become drug-resistant. Furthermore, metastatic melanoma cells did not develop drug-resistance towards the tested peptides. Thus, these host defense peptides are well suited as templates to design therapeutic leads to target drug-resistant metastatic melanoma cells.
The specific goals of this project are to expand on our preliminary results and: 1) screen toxicity of selected host defence peptides on their ability to target and kill drug-resistant metastatic melanoma cells; 2) characterise their mode-of-action; and 3) improve their therapeutic efficacy. This project will employ cell-based assays to examine toxicity, biophysical and biochemical methodologies to screen peptide-cell interaction, cellular internalization and mode-of-action (e.g. flow cytometry, confocal microscopy, surface plasmon resonance, xCelligence, incucyte, and fluorescence spectroscopy methodologies). In our group we use cultured cells, primary cells and model membranes. We are interested in characterising peptide structure and activity, cell membrane properties, peptide-lipid interactions and cancer pathways.
This project will provide new knowledge in the field of melanoma membrane biology, in drug-resistance and in peptide drug research. This research may lead to identification of specific melanoma biomarkers, development of diagnostic tools, and next generation anticancer leads to treat drug-resistant metastatic melanoma.
This project is significant because it addresses the lack of specificity, drug-resistance and side effects of current chemotherapeutics to treat metastatic melanoma. This research can advance the development of alternative leads to treat melanoma. Australia is the skin cancer capital of the world and melanoma is still one of the top 10 cancers for burden of disease in Australia.
Australian and International applicants are eligible to apply. Selected candidates will be required to apply to competitive scholarships through the Faculty of Health, QUT and will be assisted with their applications. PhD scholarships are approx. $(AUD) 27 596pa for 3.5 years full time study. PhD applicants must have completed or be expected to complete a first class hons or a Masters degree (>25% research).
Demonstrated research excellence, such as academic awards, presentations and peer-reviewed publications are desirable, but not essential.
International students must meet entry requirements for QUT https://www.qut.edu.au/research/study-with-us/how-to-apply#Step_1_Entry_requirements.
For more information about scholarships and postgraduate study at QUT https://www.qut.edu.au/research/study-with-us.