Integrative structural biology for mechanisms of protein mis-folding and dysregulation: a Japan-UK partnership between Leeds and Osaka
Lead Research Organisation:
University of Leeds
Department Name: Sch of Molecular & Cellular Biology
Abstract
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Publications
Hanson BS
(2021)
Continuum mechanical parameterisation of cytoplasmic dynein from atomistic simulation.
in Methods (San Diego, Calif.)
| Description | Better understanding and cultural links between UK and Japanese researchers |
| First Year Of Impact | 2015 |
| Impact Types | Cultural |
| Description | Computational modelling of the signalling networks established by EML4-ALK variant |
| Organisation | Osaka University |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | Experimental results and data on EML4-ALK (Prof. R Bayliss) |
| Collaborator Contribution | Computational Modelling (Prof. M Okada) |
| Impact | This is a multi-disciplinary collaboration involving maths and molecular biology. A Leeds PhD student visited Japan last year and has submitted a JSPS Fellowship application to return for 3 months. The results so far are that we have modelled the signalling of the EML4-ALK protein in lung cancer, which suggested how it might be rewired to mediate resistance. Experiments are ongoing. |
| Start Year | 2018 |
| Description | Multiscale simulations of dynein |
| Organisation | Osaka University |
| Department | Institute of Protein Research |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | Over the past 2 years, Sarah Harris and her PhD student Ben Hanson have been maintaining an active collaboration with Shinji Iida in Osaka, working with him to build a continuum representation of cytoplasmic dynein by using existing all-atom molecular dynamics simulations of the molecule. The continuum representation is necessary for modelling the motor within the Fluctuating Finite Element Analysis (FFEA) simulation framework, a recent, novel technique for the simulation of large, globular biomolecules developed in the Harris group with input from mathematicians in Leeds (Harlen). The aim of the work is to produce a method by which we can reproduce atomistic dynamics of large biomolecules, such as dynein, within a continuum framework, and therefore at a much lower computational cost. |
| Collaborator Contribution | The collaborators in Japan have contributed analysis techniques and atomistic simulation data to validate the software mentioned above. |
| Impact | Continuum Mechanical Modelling of Cytoplasmic Dynein. JSPS post doctoral fellowship application to be submitted in 2018 for Ben Hanson in collaboration with experimentalist Genji Kurisu (Osaka), to continue to link laboratory work with theoretical studies of dynein (unsuccessful). The collaboration has produced a recent paper attached to this award (Hanson et al. 2020 Methods https://doi.org/10.1016/j.ymeth.2020.01.021). The collaboration is ongoing with a visit by Hanson to Osaka planned for April 2020. |
| Start Year | 2016 |
| Description | NMR studies |
| Organisation | Osaka University |
| Department | Institute of Protein Research |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | Preparing protein samples for NMR studies in Osaka |
| Collaborator Contribution | NMR time and expertise |
| Impact | None yet |
| Start Year | 2016 |
| Description | Protein misfolding in cells |
| Organisation | Osaka University |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | Super-resolution light microscopy |
| Collaborator Contribution | Protein samples |
| Impact | None yet |
| Start Year | 2016 |