PME SPECIAL SEMINAR: Engineering Cell Fates: Newtonian and Quantum Approaches

At the most microscopic level, all biological, chemical, and physical systems are governed by the laws of quantum mechanics. At the nanoscale, quantum physics meets with classical science and generates unexplored challenges and opportunities, especially in biophysics. My work has been focused on this classical/quantum interface. During my talk, I will present two projects. In the first project, I developed ways to leverage classical mechanics to kill drug-resistant cancer cells. In the second one, I explored the potential to manipulate the spin state of magnetosensitive proteins to actuate biochemical reactions.

First, cancers are difficult to cure due to their recurrence after drug treatment. In recurrent tumors, the cancer cells that survived often develop mutations that help them resist further treatment. In ovarian cancer, recurrence, and chemoresistance are linked to elevated expression of spleen tyrosine kinase (SYK), and inhibition of SYK effectively reverses this chemoresistance. We conducted detailed investigations of how ovarian cancer cells respond to SYK inhibition and paclitaxel (PTX) chemotherapy and found that SYK inhibition significantly weakened the nuclear envelope in treated cells. PTX at therapeutic concentration induced multipolar division and multilobular nuclear morphology in cells, which leads to nuclear DNA damage and cell death if the nuclear envelope has been weakened by SYK inhibition. Through mechanically breaching the nuclear envelope, our discovery lays the foundation for a novel cancer therapy that has the potential to treat any type of chemoresistant cancer. Second, though the role of magnetic field (MF) in biology is relatively understudied, emerging evidence suggests that MF can interact with biology by modulating the spin states of radical pairs generated in flavoproteins, such as cryptochromes (CRY). We took advantage of this magnetosensitivity in CRY2, a flavoprotein widely used in optogenetics, to control cell behavior using MF.