A chiral theory of DNA supercoiling
Lead Research Organisation:
University College London
Department Name: Civil Environmental and Geomatic Eng
Abstract
We propose to bring together three threads of recent progress to develop anew chiral theory of DNA supercoiling. The three threads are i) theelectrostatic theory of interacting helical charge distributions, ii) themechanical theory of elastic braids, and iii) a new efficient approach toderive equilibrium equations for geometric variational problems. The newtheory will for the first time introduce explicitly chiral interactions intothe description of supercoiling, and will uncover the effects driven by theseinteractions. Specifically, we will build a theory to describe foursupercoiling situations: (i) spontaneous formation of free-ended braids,(ii) conformations of braided DNA in single-molecule manipulation experiments,and formation of writhes in (iii) torsionally stressed and (iv) initiallyrelaxed looped DNA, triggered by changing environment.In recent years systematic experimental studies of the torque response ofplectonemically supercoiled and braided DNA have been performed, while moreare anticipated. These require a quantitative theory that better accountsfor the complex DNA-DNA interactions. We will develop that theory. The mainpart of this project is theoretical, but the predictions of the theory willbe tested against new experiments that will be performed in collaborationwith the named Project Partners.
People |
ORCID iD |
Gert Van Der Heijden (Principal Investigator) |
Publications
Starostin EL
(2015)
Characterisation of cylindrical curves.
in Monatshefte fur Mathematik
Lee D
(2013)
Chiral effects in dual-DNA braiding
in Soft Matter
Starostin E
(2013)
Condensation of circular DNA
Starostin EL
(2013)
Condensation of circular DNA.
in The Journal of chemical physics
Starostin E
(2014)
Equilibrium Shapes with Stress Localisation for Inextensible Elastic Möbius and Other Strips
in Journal of Elasticity
Starostin E
(2014)
Theory of equilibria of elastic 2-braids with interstrand interaction
in Journal of the Mechanics and Physics of Solids
Starostin E
(2014)
Tightening elastic ( n , 2)-torus knots
in Journal of Physics: Conference Series
Description | We developed a mathematical model (elastic theory) of supercoiled DNA molecules. The model allows for interstrand interactions and is the first one not to make any assumptions on the shape of a supercoil; rather, this shape is found as part of the solution of the equations. A detailed continuum model for electrostatic DNA-DNA interactions was developed by the Imperial partner of this joint project. The combined theory was used to predict chiral (i.e., handedness) effects in DNA supercoiling. For instance we explained such chiral effects recently observed experimentally in the literature and hitherto unexplained. We also proposed new experiments where such effects might be more prominently seen in order to test the theory further. |
Exploitation Route | The theory is a general elastic theory of multi-strand structures and can also be applied to other biomolecules, polymers or other multi-strand structures (e.g., textile yarns, cables, etc.). |
Sectors | Education Pharmaceuticals and Medical Biotechnology |
Description | In the design of biophysics experiments on DNA supercoiling. |
First Year Of Impact | 2012 |
Sector | Education |
Description | Human Frontier Science Programme |
Amount | $1,200,000 (USD) |
Funding ID | RGP0049/2010 |
Organisation | Human Frontier Science Program (HFSP) |
Sector | Charity/Non Profit |
Country | France |
Start | 05/2010 |
End | 05/2013 |
Description | Biomolecular experiments (Baylor) |
Organisation | Baylor College of Medicine |
Country | United States |
Sector | Hospitals |
PI Contribution | Mechanical modelling of DNA supercoiling, DNA topology |
Collaborator Contribution | Biomolecular experiments on DNA minicircles |
Impact | HFSP grant, 3 joint posters; multi-disciplinary: mechanics + molecular biology |
Start Year | 2010 |
Description | Chiral DNA-DNA interactions (Imperial) |
Organisation | Imperial College London |
Department | Department of Chemistry |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Mechanical modelling of DNA supercoiling |
Collaborator Contribution | Physical/electrostatics modelling of DNA-DNA interaction. |
Impact | HFSP grant, 3 more joint research proposals, joint paper; multi-disciplinary: mechanics + chemistry |
Start Year | 2009 |
Description | Dual-DNA supercoiling experiments (VU Amsterdam) |
Organisation | Free University of Amsterdam |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | Mechanical modelling of DNA supercoiling |
Collaborator Contribution | Dual-DNA experiments |
Impact | HFSP grant, 3 joint posters, joint research proposal; multi-disciplinary: mechanics + biophysics |
Start Year | 2010 |