About This Project

Inside each cell, DNA wraps around histone proteins to form chromatin, which helps regulate gene activity. I study how specific H3 histone variants are arranged in stem cell nuclei. Using super-resolution 3D-STORM microscopy and custom analysis tools, I aim to uncover how these patterns shift with cell state. These insights may reveal how chromatin misregulation contributes to diseases like cancer.

Ask the Scientists

What is the context of this research?

This project investigates how DNA is organized inside cells at an extremely fine scale, which is crucial for controlling gene activity and maintaining genome stability. Previous research, such as Ricci et al. 2015 and Clément et al. 2018, revealed that DNA-associated proteins called histones form distinct tiny clusters in the nucleus using super-resolution microscopy. More recently, Arfè et al. 2025 showed that these protein clusters have specific patterns in mouse embryonic stem cells. Using 3D-STORM super-resolution microscopy, I develop computational tools to accurately measure and analyze these protein distributions in three dimensions. Understanding this organization, especially in stem cells, will provide new insights into how cells differentiate and how misregulation may lead to disease, potentially informing new therapeutic approaches.

What is the significance of this project?

This project is significant because it reveals chromatin organization at a level of detail that was previously impossible to see. Chromatin’s arrangement controls key processes like gene expression and genome stability, but conventional microscopes lack the resolution to observe structures smaller than about 200 nanometers. Super-resolution techniques like 3D-STORM overcome this limit, allowing us to visualize chromatin and associated proteins at the nanoscale. By combining this imaging with advanced computational analysis, my work uncovers spatial patterns and interactions that drive cellular function and fate. This deeper understanding could lead to breakthroughs in how we study development, disease progression, and target new therapies.

What are the goals of the project?

To address my research question, I combine wet-lab biology and computational analysis. I prepare and stain mouse embryonic stem cell nuclei using antibodies or SNAP tags to label chromatin proteins. Then, I use 3D-STORM super-resolution microscopy, which captures individual molecules’ precise locations, revealing chromatin organization at the nanoscale. After acquiring these detailed images, I apply advanced computational pipelines I developed to process and analyze the data, quantifying how proteins cluster and distribute in three dimensions. By integrating imaging and computational work, I uncover patterns of chromatin structure. I have already begun imaging and analysis and will continue refining my methods throughout the project to deepen understanding of chromatin’s role in cell function.