Investigating Subcellular Iron Fluxes in Cancer Cells by High-Resolution Fluorescence Microscopy
Gottfried Schatz Research Center (Molecular Biology and Biochemistry & Biophysics), Medical University of Graz
Prof. Dr. Roland Malli|
|Availability:||This position is available.|
Medical University of Graz
|Application deadline:||Applications are accepted between August 03, 2022 00:00 and September 20, 2022 23:59 (Europe/Zurich)|
Cellular iron supply is required for various biochemical processes but in excess iron can become highly toxic causing severe oxidative damage1. Iron is thus both vital and lethal to cells. Given this double-edged character, it is assumed that cancer cells have evolved particular strategies to maximally benefit from a cellular iron load thereby avoiding ferrotoxicity2. However, due to the lack of suitable techniques3, little is known about cancer cell type-specific dynamics of iron uptake, biodegradation, storage, subcellular transport, and efflux.
Hypothesis and Objectives:
We hypothesize that novel biosensor-based strategies will allow the high-resolution investigation of subcellular iron dynamics in cancer cells. We anticipate that illuminating the cancer cell-specific iron metabolism and homeostasis will open new avenues in the diagnosis and therapy of cancer.
The Ph.D. candidate will design, develop, generate and optimize new as well as existing fluorescent protein-based biosensors4 to detect subcellular iron transport activities and biochemical consequences thereof in cultured cancer cells in vitro using high-resolution fluorescence microscopy techniques.
1. Guo, Q. et al. The Role of Iron in Cancer Progression. Front. Oncol. 11, 778492 (2021).
2. Torti, S. V. & Torti, F. M. Iron and Cancer: 2020 Vision. Cancer Res. 80, 5435–5448 (2020).
3. Au-Yeung, H. Y., Chan, J., Chantarojsiri, T. & Chang, C. J. Molecular Imaging of Labile Iron(II) Pools in Living Cells with a Turn-On Fluorescent Probe. J. Am. Chem. Soc. 135, 15165–15173 (2013).
4. Depaoli, M. R. et al. Live cell imaging of signaling and metabolic activities. Pharmacol. Ther. 202, 98–119 (2019).