Biophysics of molecular machines that organize genomes

Project ID: 2531ad1572

(You will need this ID for your application)

UCL Lead department: Physics and Astronomy

Project Summary:

Human DNA is a linear array of billions of nucleotides, which are compacted inside cells such that genetic information is stored at the density that is million times higher than the best modern solid-state drives. Yet, genes in human DNA are continuously transcribed, replicated and repaired when they get damaged. This is achieved by the action of specialized macromolecular machines that move along DNA and physically bend and rearrange DNA using ATP hydrolysis as their energy source. In this project we will determine how these machines work by building them bottom-up and decipher how they work on different states of DNA.

Our group has been at the forefront of developing technology and studying how protein complexes from SMC family work as molecular machines. We developed new tools to apply forces to single SMC complexes and discovered how single proteins generate force (Pobegalov et al., 2023), visualized and measured how single complexes resist forces applied to DNA (Richeldi et al., 2023), and established tools to manipulate whole organelles including inside living cells (Chu et al., 2024). Our group consists of biologists, physicists and other scientists with other diverse backgrounds, which will ensure that you will learn complementary skills preparing you to be a leader in interdisciplinary research. The project can be tailored to students with biophysical, biochemical, structural biology or computational backgrounds.

This project will have two major outcomes. First, it will generate new mechanistic insights revealing mechanisms underlying molecular pathologies during gene expression, DNA recombination and cell division in diseases such as cancer and developmental disorders. Second, it will pave the way for generating artificial systems of DNA organization and information storage in DNA.