1. Please give a summary of your research.
What do you do when you’ve lost your phone in a cluttered room? Of course, you call it– letting the phone signal its location to you. In the same way, biological systems are extremely cluttered with molecules of all shapes and sizes, and medical researchers often need to single out one molecule from all the rest. My research involves developing chemicals, called sensors, which selectively interact with the molecule of interest, and emit a signal in the form of fluorescence, just like a phone emits sound. We work with biomedical researchers to identify the molecules they need to sense. Two areas in which we have made innovative advances are in studying cisplatin-based drugs, and oxidative stress.
Cisplatin and its analogues are used to treat a large proportion of cancer patients, yet its modes of action are poorly understood. Current techniques to image cisplatin in cells are insufficient– they only measure total platinum levels, therefore providing “blurry” pictures at best. We have developed the first fluorescent sensors that provide a much clearer image, letting us see where cisplatin is still active within cells, and how and where it is deactivated. This is allowing us (and other medical researchers) to understand the action of these drugs, and potentially to identify ways to improve cisplatin and decrease its side-effects.
Oxidative stress arises from a build-up of harmful reactive oxygen species (ROS) within cells, and is known to be a factor in diseases of ageing. Since ROS are also important for cellular health, it can be hard to distinguish helpful ROS from harmful oxidative stress. Our new fluorescent sensors allow us to distinguish between these two cases. Using our tools, we and our collaborators have been able to study the roles of oxidative stress in many processes including embryonic development, cancer and neurodegenerative disease.
2. Please include any additional details you would like to share
Some papers that we have published on this topic:
1.Carney IJ, Kolanowski JL, Lim Z, Chekroun B, Hambley TW, New EJ, A ratiometric iron probe enables investigation of iron distribution within tumour spheroids. Metallomics, 2018, 10, 553-556
2.Kolanowski JL, Dawson LK, Mitchell L, Lim Z, Graziotto ME, Filipek WK, Hambley TW, New EJ, A fluorescent probe for investigating metabolic stability of active transplatin analogues. Sensors and Actuators B: Chemical, 2018, 255, 2721-2724
3.Shen C, Kolanowski JL, Tran C, Kaur A, Akerfeldt MC, Rahme MS, Hambley TW, New EJ, A ratiometric fluorescent sensor for the mitochondrial copper pool, Metallomics, 2016, 8, 915-919
4.New EJ. Harnessing the Potential of Small Molecule Intracellular Fluorescent Sensors, ACS Sensors, 2016, 1, 328–333 (invited submission)
5.Kaur A, Jankowska K, Pilgrim C, Fraser ST, New EJ. Studies of hematopoietic cell differentiation with a ratiometric and reversible sensor of mitochondrial reactive oxygen species. Antioxidants and Redox Signaling, 2016, 24, 667-79. (invited submission)
6.Kaur A, Kolanowski JL, New EJ. Reversible fluorescent probes of biological redox state. Angewandte Chemie, 2016, 55, 1602–1613.
7.Kaur A, Haghighatbin MA, Hogan CF, New EJ. A FRET-based ratiometric redox probe for detecting oxidative stress by confocal microscopy, FLIM and flow cytometry. Chemical Communications, 2015, 51, 10510-10513.
8.Kaur A, Brigden KWL, Cashman TF, Fraser ST and New EJ. Mitochondrially targeted redox probe reveals the variations in oxidative capacity of the haematopoietic cells. Organic and Biomolecular Chemistry, 2015, 13, 6686-6689. Highlighted as a “Hot Article”
9.Shen C, Harris BDW, Dawson LJ, Charles KA, Hambley TW and New EJ. Fluorescent sensing of monofunctional platinum species. Chemical Communications, 2015, 51, 6312-6314.
10.Yeow J, Kaur A, Anscomb MD, New EJ, A novel flavin derivative reveals the impact of glucose on oxidative stress in adipocytes, Chem Commun., 2014, 50, 8181-8184.
My research group website: http://sydney.edu.au/science/chemistry/~enew/