Chromatin is a highly dynamic structure, yet the methods available to study it often provide only static structural snapshots or measurements averaged over millions of molecules.
This project combines single-molecule magnetic tweezers and fluorescence-coupled optical tweezers to directly manipulate and visualize individual chromatin fibers, revealing structural transitions that cannot be resolved using conventional approaches.
Capturing these dynamic events is important because chromatin is not only a passive scaffold that packages the genome within the cell nucleus, but also an active regulator of DNA accessibility during DNA replication, transcription, and repair.
The aim of the project is to understand how the organization of multiple nucleosomes – the basic repeating units of chromatin – determines chromatin’s structural and mechanical responses to tension and torsion.
To address this question, the project combines complementary single-molecule approaches into a correlative experimental platform that directly links mechanical measurements to structural changes occurring within individual chromatin fibers.
Particular emphasis will be placed on identifying the features that govern the response of chromatin to torsional stress.
Genomic DNA is continuously twisted during transcription, and the resulting supercoiling must be tightly controlled to preserve genome function.
While the cellular pathways responsible for maintaining DNA topology have been studied extensively, the contribution of chromatin itself remains poorly understood.
Determining how different levels of chromatin organization influence its response to torsional stress may uncover an unexplored physical layer of genome regulation.
The proposed research is highly multidisciplinary, integrating molecular biology, biophysics, and quantitative data analysis.
The student will gain hands-on experience in chromatin reconstitution, advanced single- molecule force spectroscopy coupled with fluorescence microscopy, computational modelling, and scientific programming.
Together, these approaches will provide a comprehensive framework for investigating the physical principles governing chromatin organization and dynamics.