Study level
- PhD
Faculty/School
Faculty of Health
Topic status
We're looking for students to study this topic.
Supervisors
- Position
- Pro Vice-Chancellor (Research Infrastructure)
- Division / Faculty
- Academic Division
- Position
- Associate Professor
- Division / Faculty
- Faculty of Health
Overview
Cell membrane structure and function are altered during tumour development, but to date comprehensive studies on the characterisation of cell membranes of a given cancer are scarce, or are only focused on a particular property (e.g. overall charge, global lipid composition, or specific lipid). In preliminary work we compared the lipidome (i.e. the lipid profile) of a panel of cells, and found the lipid composition of model melanoma cells to be distinct from that of other cancerous and non-cancerous cells. In addition, we found peptides that selectively target melanoma cell membranes. These observations suggest that cell membrane components can be targeted to increase selectivity of anticancer drugs towards cancer cells.
Aims and hypotheses
Based on our preliminary work we hypothesise that the lipid composition and properties of cancer cell membranes are distinct from those of healthy cells can be used as alternative therapeutic targets and as diseases stage biomarkers. In this project we propose to expand our preliminary work and to do an integrated characterisation of melanoma cell membranes, including lipid diversity, distribution, organisation, overall membrane biophysics and how those properties relate to cancer progression and drug-resistance. This will be achieved by focusing on three aims: 1) Characterisation of lipid diversity (e.g. phospholipids head-groups and acyl chains); 2) Identification of lipid organisation within cell membranes (e.g. lipid segregation, and distribution within inner and outer leaflets); and 3) Characterisation of overall cell membrane properties (e.g. fluidity, charge and tumour invasiveness).
Research plan and methods
- Aim 1: Characterisation of lipid diversity. The lipid diversity is important for the structure and biological function of cell membranes. We will use in vitro models of melanoma cells at different disease stages and of non-cancerous cells, including commercially available primary keratinocytes and melanocytes. Lipidomic characterisation will be done using mass spectrometry.
- Aim 2: Identification of lipid organisation within cell membranes. In membranes of healthy cells only neutral lipids are surface exposed, whereas cancer cells are often characterised by a more negatively-charged surface. To investigate whether there are specific lipids exposed at the cell surface of melanoma cells and if they vary with disease stage and with acquired drug-resistance, we will characterise the distribution of lipid classes and species between the two layers in the cell membrane of a panel of cells. This will be investigated using flow cytometry, fluorescence spectroscopy and confocal microscopy.
- Aim 3: Overall cell membrane properties. To understand how lipid diversity and organisation affects cell membrane properties, we will characterise surface charge, overall fluidity and dynamics of cell membranes. These biophysical properties will be compared to identify trends in melanoma disease stages and drug-resistance. Surface charge of cells will be determined using zeta potential measurements, whereas fluidity will be characterised using fluorescence spectroscopy and microscopy with membrane dyes.
Expected outcomes
With this project we will identify lipids and/or membrane properties that can be used as alternative therapeutic targets, to guide drug discovery, and to help monitor cancer progression and drug-resistance.
Clinical significance/commercial impact
New knowledge on cancer membrane will inform the design of more specific anticancer therapeutic leads, such as targeted drugs designed to selectively attack cancer cells.
Keywords
Contact
Contact Dr Sonia Troeira Henriques for more information.
Email: sonia.henriques@qut.edu.au; Phone: +61 7 34437342