May C Morris
Institut des Biomolecules Max Mousseron, France
Title: Fluorescent carbon nanotube biosensors for probing intracellular kinase hyperactivation in human cancer
Biography
Biography: May C Morris
Abstract
Cyclin-dependent kinases (CDK/Cyclins) play a central role in coordinating cell growth and division and are frequently deregulated in cancer, thereby constituting proliferation biomarkers and attractive pharmacological targets. However, probing and quantifying the hyperactivity of these kinases remains challenging, and there are no technologies available to monitor their activity in living cells in a non-invasive fashion. To this aim, we have developed a family of fluorescent biosensors, known as CDKACT, through conjugation of environmentally-sensitive probes to synthetic peptides which are specifically recognized by CDK/Cyclins and undergo fluorescent enhancement upon phosphorylation. We have further conjugated these peptide biosensors at the surface of multiwall carbon nanotubes to obtain self-cell-penetrating sensors of intracellular kinase activity. We show that these carbon nanotube peptide conjugates report on CDK/Cyclin activities in a sensitive and robust fashion in vitro. Moreover, these nanobiosensors penetrate readily into living cells and enable detection and quantification of the intracellular activities of these kinases by fluorescence imaging. This new generation of hybrid carbon nanotube peptide biosensors constitute attractive tools for cancer diagnostics and for evaluating response to therapeutics. They are particularly well suited for molecular imaging and are currently being implementing to monitor CDK/Cyclin hyperactivity associated with cancer progression and inhibition in mouse cancer models