chemical probes for biology
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, which can be studied by confocal microscopy, or that alter the relaxation rate of water protons, which can be used for MRI studies. My interests lie in developing small molecule probes for studying redox state and metal ions, and applying these probes to answer questions of biological relevance.
MRI probes for redox state
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 work with collaborators to use our probes in models of heart attack. This work will involve the synthesis of Gd complexes, NMR experiments and biological studies.
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 based on organic fluorophores, metal complexes or on FRET pairs. We will then use these probes to study models of disease in cultured cells. This project is particularly suited to students interested in combining synthesis with spectroscopic experiments, with optional biological studies.
Fluorescent sensors for metal ion
Almost all biological processes require metal ions for correct functioning, particularly as cofactors in many enzymes. Cells must therefore be able to maintain a readily-available pool of metal ions which can be acquired by newly-forming proteins. If metal levels in these pools are too low, enzymes will lose function, while if they are too high, incorrect metal complexes can form, leading to diseases like Alzheimer’s. We will design fluorescent sensors that bind selectively to Ni(II), Mn(II), Cu(I) or Cu(II) and report on the presence of the ion by a characteristic change in fluorescence emission. We will study the behaviour of these probes by spectroscopy, and in simple biological systems, and then use them to understand how cells regulate metal levels. This project will involve synthesis, fluorescence spectroscopy and biological study, with a focus on bioinorganic chemistry.
For further information, please contact:
School of Chemistry
University of Sydney NSW 2006
Phone: +61 2 9351 1993