PhD project: Shaping the genome through formation of protein droplets
Project description
Liquid-liquid phase separation is a phenomena which has been studied by physicists for decades. We see many examples in our everyday life: droplets of oil forming in (mostly) water in a salad dressing, or bubbles of gas in a fizzy drink. Recently, this same physical mechanism has been discovered to play a crucial role in the formation of 'droplets' of different kinds of proteins within biological systems. These droplets are thought to be useful for segregating different molecules, controlling their interactions, and facilitating chemical reactions essential for cellular function.
For many biological structures, membranes are used to keep different biological components together or apart; but these protein droplets self-assemble through phase separation without requiring any containing membrane. We are interested in protein droplets that interact with and influence the genome—the DNA within our chromosomes. Our DNA contains the instruction set or genetic code which tells our cells how to grow and function, and its spatial organisation within the cell nucleus plays an important role in controlling that function.
In this computational biophysics project you will study the physics behind the formation of protein droplets which drive chromosomes into different structures. Possible directions of the work include:
- Understanding how protein-DNA interactions control the mesoscopic physical properties of chromosome structure, and the implications this has for gene regulation.
- Studying how chemical reactions which drive the system out of equilibrium alter the properties of the droplets, and how this can control their formation and play a role in different processes.
- Uncovering the link between the details of the protein-DNA interactions and the indirect experimental measurements which can be made in vivo (i.e., inside living cells) and in vitro (i.e., in more controlled conditions in the lab).
While the work will primarily be computational, depending on the interests of the student there is scope for collaboration with experimentalists. This could be working with data from molecular biology collaborators within or outside the university, or doing some biophysics experiments with colleagues in the school of physics.
Some relevant references:
- M. Ancona and C. A. Brackley "Simulating the chromatin mediated phase separation of model proteins with multiple domains" Biophysical Journal 121 2600-2612 (2022) link
- C. A. Brackley "Polymer compaction and bridging-induced clustering of protein-inspired patchy particles" Journal of Physics: Condensed Matter 32 314002 (2020) link
- C. A. Brackley, B. Liebchen, D. Michieletto, F. L. Mouvet, P. R Cook and D. Marenduzzo "Ephemeral protein binding to DNA shapes stable nuclear bodies and chromatin domains" Biophysical Journal 28 1085 (2017) link
- B. Wang, et al. "Liquid–liquid phase separation in human health and diseases" Signal Transduction and Targeted Therapy 6 290 (2021) link
- F. Erdel, et al. "Formation of Chromatin Subcompartments by Phase Separation" Biophysical Journal 114 2262-2270 (2018) link
Project supervisor
- Dr Chris Brackley (School of Physics & Astronomy, University of Edinburgh)
The project supervisor welcomes informal enquiries about this project.
Find out more about this research area
The links below summarise our research in the area(s) relevant to this project:
- Find out more about Physics of Living Matter.
- Find out more about the Institute for Condensed Matter and Complex Systems.
What next?
- Find out how to apply for our PhD degrees.
- Find out about fees and funding and studentship opportunities.
- View and complete the application form (on the main University website).
- Find out how to contact us for more information.