Large Scale Lattice Boltzmann for Biocolloidal Systems
Lead Research Organisation:
University of Edinburgh
Department Name: Sch of Physics and Astronomy
Abstract
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Organisations
- University of Edinburgh (Lead Research Organisation)
- Biotechnology and Biological Sciences Research Council (Co-funder)
- University of Cologne (Collaboration)
- University of Lausanne (Project Partner)
- ETH Zurich (Project Partner)
- University of Bath (Project Partner)
- Newcastle University (Project Partner)
- University of Oxford (Project Partner)
Publications
Brackley CA
(2015)
Topological constraints strongly affect chromatin reconstitution in silico.
in Nucleic acids research
Brackley CA
(2013)
Intracellular facilitated diffusion: searchers, crowders, and blockers.
in Physical review letters
Brackley CA
(2013)
Effect of DNA conformation on facilitated diffusion.
in Biochemical Society transactions
Brackley CA
(2013)
Nonspecific bridging-induced attraction drives clustering of DNA-binding proteins and genome organization.
in Proceedings of the National Academy of Sciences of the United States of America
Brackley CA
(2012)
Facilitated diffusion on mobile DNA: configurational traps and sequence heterogeneity.
in Physical review letters
Brackley CA
(2016)
Simulated binding of transcription factors to active and inactive regions folds human chromosomes into loops, rosettes and topological domains.
in Nucleic acids research
Brackley CA
(2014)
Models for twistable elastic polymers in Brownian dynamics, and their implementation for LAMMPS.
in The Journal of chemical physics
Brackley CA
(2016)
Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models.
in Genome biology
Brant L
(2016)
Exploiting native forces to capture chromosome conformation in mammalian cell nuclei.
in Molecular systems biology
Johnson J
(2015)
A simple model for DNA bridging proteins and bacterial or human genomes: bridging-induced attraction and genome compaction.
in Journal of physics. Condensed matter : an Institute of Physics journal
| Description | This grant is now finished. During the grant we have: (i) provided new large scale simulations of the process through which proteins search their target within the cell, taking into account macromolecular crowding for the first time; (ii) discovered a new mechanism through which molecular bridges which bind to the DNA or chromosomes in multiple points cluster together and organise in turn the structure of the genome. This second result has raised the interest of several (4 already, in France, Edinburgh, Oxford and Harvard - the latter now in University of Kashmir) experimental groups, who asked us to help them analyse their data on chromosome contacts in Drosophila, human, mouse and plants within the framework of our model. After the grant ended, we have pursued actively most of these, and now we have two published papers, and one submitted, with researchers in Oxford and Kashmir. Through the Oxford collaboration, we have been able to test the predictions of our chromosome model with Fluorescence In-Situ Hybridisation data, finding good agreement. The work during this grant has also helped the PI find additional funding through an ERC Consolidator Grant (start date July 2015). |
| Exploitation Route | As mentioned above our work can underpin further progress in molecular cell biology; it could also have some impact in biomedical science as the structure of chromosomes differs during development, and in diseased cells. Our chromosome conformation models have already had a significant impact within the community, with more requests for collaboration at each new conference. We have now uploaded an example of such collaboration (with A. Papantonis's group in Cologne). |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| Description | Collaboration with Argyris Papantonis |
| Organisation | University of Cologne |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | We performed simulations of chromatin conformation following immune response (in particular we studied a gene important for the immune response, SAMD4A, found in chromosome 14 of the human genome), which our collaborators (Argyris Papantonis and his group) were working on experimentally. This collaboration came up as the Papantonis group saw work which came after the end of the EPSRC award Large Scale Lattice Boltzmann for Biocolloidal Systems, which was related to that award (Genome Biology, 17, 1 (2016)). The joint work resulted in the publication of one paper, Lilija Brant, Theodore Georgomanolis, Milos Nikolic, Chris A Brackley, Petros Kolovos, Wilfred van Ijcken, Frank G Grosveld, Davide Marenduzzo and Argyris Papantonis, Molecular Systems Biology, 12, 12, p. 891 (2016). |
| Collaborator Contribution | Our collaborators contributed chromosome conformation capture (4C and HiC) to the project. |
| Impact | . The joint work resulted in the publication of one paper, Lilija Brant, Theodore Georgomanolis, Milos Nikolic, Chris A Brackley, Petros Kolovos, Wilfred van Ijcken, Frank G Grosveld, Davide Marenduzzo and Argyris Papantonis, Molecular Systems Biology, 12, 12, p. 891 (2016). |
| Start Year | 2016 |