Developing image driven treatment paradigms for brain cancer & Single-Enzyme Kinetics with Fluorogenic Substrates
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Dr Simon Puttick Primary brain tumours account for 1-2 % of all diagnosed cancer in Australian adults and 9 % of all cancers in Australian young people. Compared with other cancers, primary brain tumours are the leading cause of cancer death in people under the age of 40 and the leading cause of death in children under the age of 14. There is a very limited knowledge of risk factors for primary brain tumours and no early screening procedures are available. As such, clinical management of primary brain tumours and the development of new, effective therapies relies heavily on medical imaging biomarkers. In this presentation I will talk about our recent developments in PET and MRI imaging to image the tumour microenvironment and how we are applying these techniques to the development of effective treatment paradigms for brain cancer. Dr Petri Turunen Single-molecule fluorescence techniques have developed into powerful tools for studying the kinetics of biological reactions. Using fluorogenic substrates, enzymatic reactions can be observed in real-time with single-turnover resolution. Despite their clearly proven potential, the accuracy of single-turnover measurements is currently limited by the availability of substrates with 1:1 stoichiometry and the signal-to-noise ratio (SNR) of the measurement. The SNR also defines the range of substrate concentrations, frequently prohibiting measurements above the KM value. If restricted to concentrations below the KM, substrate diffusion might become the rate-limiting step and determine the kinetic behavior of the enzyme. New strategies are needed to be able to perform more accurate single-enzyme experiments in more biologically relevant conditions. As a step towards improving the substrate design, we have designed and characterized a series of FRET-labeled peptide substrates for studying protease kinetics at the single-molecule level. We have further implemented a detection scheme based on zero-mode mode waveguide (ZMW) nanostructures. ZMWs possess a drastically reduced detection volume and can enhance the fluorescence signal, thereby increasing the SNR and extending the range of substrate concentrations. In this talk I will present our efforts to improve single-molecule enzymology with fluorogenic substrates and discuss future directions in the field. |
About AIBN Seminar Series
The AIBN Seminar series showcases a range of seminars across different topics and disciplines