MRC Human Genetics Unit
Medical Research Council Human Genetics Unit

Davide Michieletto Research Group (Affiliate)

Topology and Viscoelasticity of DNA and Genomes

Section: Genome Regulation

Davide Michieletto
Dr Davide Michieletto, Royal Society University Research Fellow

Research in a Nutshell 

In spite of their extreme length and confinement our genomes are surprisingly well organised, functional and relatively free of knots. Inspired by this, we are interested in understanding how DNA topology is regulated in vivo, e.g. by Topoisomerase, Recombinase and SMC proteins, and while doing so we aim to discover new soft materials.

We believe that the topology and viscoelasticity of DNA and chromatin are important – yet under-explored -- elements that regulate genome function. As an example, imagine a gene that is turned on in response to an external stimulus: specific regions such as promoters and enhancers must be rearranged within the nuclear environment while avoiding getting stuck or entangled. It may sound impossible but this problem is akin to that of squeezing mayonnaise out of a bottle and it has to do with how polymers – long chains of monomers -- move in space and relax entanglements.

Another example is that of phase separated condensates: they are far from simple liquids and instead display complex viscoelastic behaviours that are only starting to be uncovered (Jawerth et al, Science 2020) and likely protein-dependent. The relationship between the material properties of these condensates and their function is an exciting avenue for new collaborations. 

 

People

 
Davide Michieletto Group Leader
Cleis Battaglia PhD student
Edward Brown PhD student
Simon Weir PDRA

Contact

davide.michieletto@ed.ac.uk

Website

Davide Michieletto (ed.ac.uk)

Collaborations

  • Professor Nick Gilbert, University of Edinburgh 
  • Professor Rae Robertson-Anderson, University of San Diego
  • Professor Cees Dekker, TUDelft

Partners and Funders

  • ERC
  • Royal Society
  • SULSA
  • Leverhulme Trust

 

Scientific Themes

Theoretical and Computational Soft Matter, Viscoelasticity of complex fluids

Technology Expertise

Molecular Dynamics Simulations of DNA and Chromatin, Microrheology, Super-Resolution Microscopy