Crowding-Induced Effects on Structural Dynamics, Photophysics and Photochemistry of a Porphyrin-Based Photosensitizer Bound to a G-Quadruplex Proto-Oncogene—Implications for Photodynamic Therapy.

• Applicant: Dr. Avinash Chettri, Ph.D.
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 580076059

Photodynamic therapy (PDT) is a non-invasive cancer treatment where a photosensitizer (PS) generates reactive oxygen species (ROS) upon light exposure, destroying cancerous cells. However, a comprehensive understanding of how the cellular environment affects a PS's photophysical properties is lacking, as current assessments are performed in dilute solutions that don't mimic the crowded intracellular environment. The Walter Benjamin project will address this gap by investigating the effects of crowding on the structural dynamics and photophysics of a porphyrin-based PS, TMPyP4, and a guanine quadruplex (GQ) of the c-myc proto-oncogene, whose overexpression is linked to several cancers. By employing visible transient absorption and time-resolved infrared spectroscopy, the project will capture real-time snapshots of the PS's excited-state dynamics, structural changes at the c-myc GQ binding site, and environmental effects on ROS-mediated photoreactions within a crowded, cell-like environment. This systematic approach will enhance our understanding of how to optimize PDT drug design, enabling new strategies to combat cancer. The scientific and non-scientific activities in the project are strategically designed to open up opportunities for the candidate to merge complementary benefits of time-resolved visible and IR techniques to answer fundamental questions on rational drug-design for PDT, enhance his understanding on dynamics of biomolecules in complex cell-like environment and generate collaboration with clinics and pharmaceutical industries. These skillsets and resources will elevate the candidate's status to an independent researcher with a well-rounded expertise on understanding the dynamics of PDT-relevant drugs and biological systems, allowing him to validate / modify in silico models on drug-environment interaction-a step towards improving medical health care.

• DFG Programme: Fellowship
• International Connection: Sweden
• Host: Professor Dr. Michal Maj, Ph.D.