Project description
Microscopy at physiological oxygen levels
Drug research and development is replacing standard plate-reader assays with microscopy screening. Combined with innovative functional assays, it is possible to monitor dynamic events in living cells. The EU-funded MICROX will work on microscopy-assays that resemble the real oxygen levels that our cells encounter. Conventional protocols maintain cells at 21 % oxygen, whereas physiologically most cells are exposed to 2-5 % oxygen and cancer cells to hypoxic conditions. The resultant MICROX microscopy platform will offer the capacity to adjust atmospheric conditions according to cell type, and importantly, facilitate the discovery and screening of anticancer drugs.
Objective
Functional evaluation of bioactive compounds using cell-based assays is key in discovering new and improved drugs to address our societies growing medical needs. In a large number of academic and private R&D facilities around the world, hi-content microscopy screening is used to complement and often outperform the conventional luminescence and fluorescence plate-reader assays. The combination of fluorescent-probe technology, modern optical microscopes and innovative functional assays allows monitoring highly dynamic events in living cells with exquisite temporal and spatial resolution.
Remarkably, drug candidates and treatment regimens are commonly tested on living cells maintained at atmospheric oxygenation levels (i.e. at 21% O2) while in reality, cells in our bodies never experience such high oxygen levels. Rather, most cells experience 2-5% of O2 and cancer cells in solid tumours are generally hypoxic, i.e. they function at < 1% of O2. It has become evident that oxygenation of the preparation dramatically affects efficacy of our drugs, in particular of cancer treatments. Thus, there is an urgent need to establish functional microscopy assays for (cancer)drug efficacy at hypoxic conditions.
However, it is not trivial to enclose the necessary high-end microscopes in O2-tight incubators while maintaining good access to the cells. In this project, experienced biochemist and pharmacologist dr. Olga Mazina aims to team up with the advanced microscopy group of prof. Kees Jalink to establish an innovative MICROX microscopy platform with fully adjustable atmospheric conditions, along with a panel of biosensors optimized for use at hypoxia. MICROX will be developed in close collaboration with leading European manufacturers and validated in studies addressing cancer cell signalling and sensitivity to cancer drugs at various O2 levels.
Fields of science
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensorsbiosensors
- natural sciencesbiological sciencescell biologycell signaling
- natural sciencesphysical sciencesopticsmicroscopy
- medical and health sciencesclinical medicineoncology
Programme(s)
Funding Scheme
MSCA-IF-EF-CAR - CAR – Career Restart panelCoordinator
1066 CX Amsterdam
Netherlands