chemical probes for biology
Our research is focussed on using chemical tools to answer important biological questions. Chemical probes help us to gather information about specific molecules or reactions within a cell, with high spatial resolution and sensitivity. Probes can be designed that give information by fluorescence output (for confocal microscopy) or that alter the relaxation rate of water protons (for MRI studies). Our interests lie in developing small molecule probes for studying oxidative stress and metal ions, and applying these probes to answer questions of biological relevance.
The projects outlined below will be ideal for students who are interested in the applications of organic and inorganic synthesis. Students will receive broad-based training in experimental techniques, as they will take their compounds all the way from design and synthesis to spectroscopic experiments and biological testing.
MRI probes for oxidative stress (with Dr Paul Bonnitcha, Kolling Institute of Medical Research)
Variations in biological redox state can lead to a range of pathological conditions including hypertensive disease and diabetes. MRI offers the possibility of non-invasive, 3D imaging in live animals. Contrast agents, often containing Gd(III), are commonly used to amplify the signal. We will develop Gd(III) complexes for use as MRI contrast agents that are responsive to redox state. After performing spectroscopic studies of solutions and cell suspensions, we will test our probes in commercial MRI machines. We will then use our probes in models of heart attack.
Fluorescent sensors for redox state
Fluorescent probes enable us to use confocal microscopy to observe events within cells. To date, only a few small molecule fluorescent redox sensors have been developed, but they haven’t seen much use in biological studies. In this project, we will design and synthesise new redox probes, and then use these probes to study models of disease in cultured cells.
Fluorescent sensors for metal ion
Almost all biological processes require metal ions for correct functioning, particularly as cofactors in many enzymes. If metal levels are too low, enzymes will lose function, but if they are too high, incorrect metal complexes can form, leading to diseases like Alzheimer’s. We will design fluorescent sensors for metal ions such as Ni(II), Mn(II), Cu(I) and Cu(II) that will allow us to understand the roles of metals in disease.
Fluorescent sensing methods for platinum (with Prof Trevor Hambley)
Platinum-containing drugs are amongst the most important cancer therapeutic agents, but platinum-based chemotherapy is often accompanied by toxicity, especially of the kidneys. Currently, measurements of blood platinum levels require ICP-MS, which is very expensive for hospitals to purchase and run. In this project, we will develop new fluorescent methods to measure platinum levels both in blood and in cells.
Fluorescent sensors for iron (with Prof Trevor Hambley)
Iron is one of the most essential elements for life – it is the most abundant transition metal in biology. Dietary iron is stored in the liver and released to the plasma pool for use in proteins such as haemoglobin, but misregulated iron levels can play a role in many diseases, including liver disease and cancer. Despite its importance, iron is one of the most difficult metals to sense. This project will involve the development of new fluorescent sensors for iron which will enable us to search for new roles for iron in disease.
For further information, please contact:
School of Chemistry
University of Sydney NSW 2006
Phone: +61 2 9351 1993