PhD project: Theory and Multiscale Simulations of DNA and Chromatin
Project description
DNA [1] is arguably one of the most important biopolymers, as its sequence encodes the genetic instructions needed in the development and functioning of living organisms. While we now know in detail the sequence of many genomes, including that of humans, we know little as to how DNA folds up in the 3-dimensional space inside a living cell. To give an idea of the complexity, think that the total DNA enclosed in the nucleus of one of your cells, which is about ten microns or so in diameter, would span, if stretch out, more than a meter! To solve this daunting confinement problem, DNA interacts with a variety of proteins to decrease its radius of gyration.
We wish to understand how DNA organises in space, especially in the presence of proteins which bind to and move along it. An important example is the formation of chromatin, the form in which DNA exists in the nuclei of all eukaryotes, such as humans. Chromatin [2] is a fiber made up by histone proteins around which the DNA wraps essentially due to electrostatic
interactions. Little is known either about the higher order structure of chromatin, or even how it self-assembles in the cell or in the test tube.
For this project we will build on existing models and codes which describe DNA at various length scales (or levels of coarse graining). These will range from models in which DNA is viewed as an elastic and fluctuating biopolymer [3], to more detailed ones [4] in which its double stranded and helical structure is captured. Possible projects include the study of chromatin under different ionic conditions, the self-assembly of chromosome fragments, and the behaviour of DNA in the presence of molecular motors which transcribe it (polymerases). We will also be concerned with the effect of hydrodynamic interactions on all these phenomena.
[1] Understanding DNA. D. R. Callidine and H. Drew. Academic Press, Oxford (1997).
[2] The physics of chromatin. H. Schiessel, J. Phys. Condens. Matt. 15, R699 (2003).
[3] Facilitated diffusion on mobile DNA: Configurational traps and sequence heterogeneity. C. A. Brackley, M. E. Cates, D. Marenduzzo. Phys. Rev. Lett. 109 168103 (2012).
[4] Structural, mechanical and thermodynamic properties of a coarse-grained DNA model. T. E. Ouldridge, A. A. Louis and J. P. K. Doye, J. Chem. Phys, 134, 085101 (2011).
Project supervisor
- Professor Davide Marenduzzo (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 Computational Materials Physics.
- 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.