Melike Berksöz

Hi there ! I am a postdoctoral researcher at MIDST Lab, Sabanci University. My current research focuses on understanding the allosteric regulation mechanism in various protein-based sensors. These genetically engineered tools can be used to track virtually any analyte in a cell via live-cell fluorescence microscopy. They are constructed with a modular design, where ligand binding triggers allosteric changes that affect their spectral characteristics. The prevailing view is that an analyte binding event in the sensing domain triggers a conformational change in the reporter domain (fluorescent protein), causing the sensor to respond to the presence of the ligand.

A major challenge in creating novel sensors lies in predicting—based on static structures or, worse still, sequence data only—how a given design will behave in the cell and whether it will respond to the analyte. To elucidate the key factors dictating sensor performance, I analyzed both “good” and “bad” sensors in terms of their conformational dynamics. To that end, I employ molecular dynamics simulations and free energy calculations. I identified a few key structural metrics that make a sensor highly efficient which can be used to rank different sensor constructs in silico and reduce experimental screening times. Recently, we discovered that allosteric hot spots predicted by Perturbation Response Scanning can accurately pinpoint viable sites best suited to communicate conformational changes to the reporter domain.

In addition to computational biophysics, I have been involved in various aspects of experimental structural biology. During my Master’s studies at Albert-Ludwigs University of Freiburg, I explored the conductance mechanism of bacterial ion transporters using electrophysiology. In this method, the isolated membrane protein is reconstituted into a liposome, and spontaneous ion passage from the outside to the inside of the liposome is measured as electrical current.

Before beginning my PhD, I gained experience in industrial research related to drug production. I worked at a newly established biotech lab of İlko Pharmaceuticals in Teknopark, İstanbul, contributing to various development stages of therapeutic antibodies, from cell line development to process scale-ups. I developed biophysical methods to characterize structural integrity, post-translational modifications, and the stability of these antibodies. Owing to the strict regulations in biologics production, I devoted a great deal of effort to validating these methods to ensure they were accurate and reproducible.

Besides my scientific endeavors, I enjoy swimming and reading world literature.