EPSRC Research Software Engineer Fellowship Oliver Henrich

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Physics and Astronomy

Abstract

The interdisciplinary programme of research and software development I propose lies at the interface of physics, chemistry, and biology. Key target areas of this proposals, which my software will address, are coarse-grained modelling of DNA and RNA, the study of living systems and active matter far away from equilibrium, new soft energy and functional materials, enhanced encapsulation technologies and algorithms for new heterogeneous computing architectures.

The proposed software development programme aligns with a number of key areas of research that have been identified as Physics Grand Challenges. One of them is the understanding the physics of life. This has the goal to develop an integrating understanding of life from single molecules to whole biological systems. DNA and RNA are the two biopolymers that are involved in various biological roles, most notably in the encoding of the genetic instructions needed in the development and functioning of living organisms and gene transcription. Coarse-grained models of DNA or RNA can provide significant computational and conceptual advantages over atomistic models, leading often to three or more orders of magnitude greater efficiency. But they are not only an efficient alternative to atomistic models of DNA as they are indispensable for the modelling of DNA on timescales in the millisecond range and beyond, or when long DNA strands of tens of thousands of base pairs or more have to be considered. This is for instance important to study the dynamics of DNA supercoiling, the local over- or under-twisting of the double helix, which is important for gene expression.
Another Grand Challenge is the nanoscale design of functional material, which aims at engineering desired properties into the materials by using new principles rather than proceeding by trial and error. In the proposed programme I address different classes of functional and energy materials. One example are particle suspensions, which are fundamental in encapsulation technologies used in consumer products like foods, beverages, cleaning agents, personal care products, paints and inks or in the petrochemical industry or the micro-technological sector with lab-on-a-chip devices. Nanostructured charged soft materials are a new and highly promising avenue to more efficient, safer energy producing or storing devices and have great potential to fill technological gaps in the design of batteries and electrodes or the storage of renewable energy.
A third Grand Challenge is the emergence and physics far from thermodynamic equilibrium. As life itself is a process far away from equilibrium, the context of this research is also closely related to aspects of living matter and often challenges the classical theories of statistical physics.

The software that I will produce during this Fellowship will be open source and freely available for download from public repositories. Parts of it are likely to form later a key contribution to a highly optimised and standardised library of micro-, meso- and macroscale algorithms and a European infrastructure for the simulation of complex fluids. The software and research programme will be undertaken at the University of Edinburgh in collaboration with project partners at the University of Cambridge, the University of Oxford, University College London, the University of Barcelona, Spain and Sandia National Laboratories, USA.

Planned Impact

We are currently undergoing a transition to a new economy, which will be characterised by a deep and detailed understanding of the functioning mechanisms of DNA, RNA and their interaction with proteins. This transition will create new opportunities and industries and will have a transformative character on our societies, similar to that of the automotive, telecommunication and computer industry.

A concrete example of genetic technologies is genetically modified foods that have allowed for the introduction of new crop traits and far greater control over a food's genetic structure than previously afforded by traditional methods like selective breeding and mutation. An emerging example is personalised medicine, the customisation of healthcare using molecular analysis and a patient's genetic information for tailored gene therapies and medical decisions. The fundamental insights that my software will enable will undoubtedly create opportunities for improvement and enhancement of the two above mentioned, well-established applications of genetic technologies and open up completely new possibilities.

Recently, non-biological applications such as DNA-nanotechnology have sparked great interest, and the sequence-specific coarse-grained models for DNA and RNA are directly targeting this field. DNA origami for example is the programmable bottom-up approach of designing nanoscale materials and two- and three-dimensional shapes in a self-assembled manner by using the specificity of the interaction between complementary base pairs. There is great desire among experimentalists to get a computational feedback that is needed to reduce the financial cost and time required to design nanoscale self-assembled materials. Coarse-grained DNA models are the only candidates that could fill this technological gap.

The nanoscale design of new functional soft materials is another focus of this proposal. Particle suspensions are fundamentally important for encapsulation technologies in consumer products like foods, beverages, cleaning agents, personal care products, paints and inks or in the petrochemical industry or micro-technological sector with lab-on-a-chip devices. Nanostructured charged soft materials are a new avenue to more efficient energy producing or storing devices and have great potential to fill technological gaps in the design of batteries and electrodes or storage of renewable energy. But before these insights can be turned into a competitive advantage for our industrial collaborators a detailed understanding of the behaviour of these systems needs to be first acquired. This can only be achieved through accurate descriptions of the complex morphology and dynamics of their different constituents, which my software will enable.

The field of active matter is very new and burgeoning with novel scientific insights that challenge the traditional beliefs of statistical physics and sometimes constitute new physics. The consequences of this are rather profound and can only be probed by a body of numerical simulations that account for all non-linearities and couplings in the underlying equations of motion.

While the software that I will develop is essential for the research community of computational soft matter and biological physics, the impact of the research originating from this software will often go beyond academia. I envisage its use will extend to many other communities. I anticipate that engineers, material scientists, physical chemists, biochemists, cell or molecular biologists as well as workers in industry are likely to engage in the future with many of the codes which I will provide. The software will be open source and also form an essential contribution to a future European infrastructure for the simulation of complex fluids.

Publications

10 25 50

Related Projects

Project Reference Relationship Related To Start End Award Value
EP/N019180/1 31/07/2016 30/06/2017 £489,605
EP/N019180/2 Transfer EP/N019180/1 01/07/2017 31/07/2021 £409,704
 
Description Although the award is still active, one key result has been the implementation and upgrade of the oxDNA code into the LAMMPS code. The model is now provided as a USER-package and available for download from the central LAMMPS repository. We applied the model to simulate single-stranded DNA, an area which has so far been under-investigated. I am also working on a direct comparison between different coarse-grained DNA models with new colleagues at the University of Strathclyde, Glasgow.
Exploitation Route The software is in use at the University of Strathclyde, Glasgow, the University of Edinburgh, University of Oxford and at SISSA, Trieste, Italy. Current applications include DNA supercoiling and DNA hybridisation. I expect the range of applications to increase substantially over the coming years.
Sectors Agriculture, Food and Drink,Digital/Communication/Information Technologies (including Software),Energy,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL http://lammps.sandia.gov
 
Title LAMMPS implementation of the oxDNA model 
Description The oxDNA model is now available through the LAMMPS code, which is a community code for molecular dynamics simulations 
Type Of Material Improvements to research infrastructure 
Year Produced 2017 
Provided To Others? Yes  
Impact It is too early to state any concrete impact. However, I had a few requests from the UK, Europe and the USA about the usage of this implementation, etc. 
URL http://lammps.sandia.gov/doc/Section_packages.html#user-cgdna-package
 
Description Implementation of the oxDNA model into the LAMMPS code 
Organisation Imperial College London
Department Department of Bioengineering
Country United Kingdom 
Sector Academic/University 
PI Contribution The implementation was carried out by myself. I was also the lead scientist on a documenting article about this implementation.
Collaborator Contribution Dr Thomas E. Ouldridge helped with the implementation and verification of the code and provided consulting services for applications.
Impact The oxDNA model has been implemented into the LAMMPS code and is available for download from the central LAMMPS repository.
Start Year 2016
 
Title LAMMPS package USER-CGDNA 
Description LAMMPS is a classical molecular dynamics code, and an acronym for Large-scale Atomic/Molecular Massively Parallel Simulator. The oxDNA model for coarse-grained modelling of DNA is now also available as LAMMPS USER-package. 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact The oxDNA model is now more easily accessible to a global user community of the LAMMPS code. 
URL http://lammps.sandia.gov
 
Title Ludwig Soft Matter Simulation Software 
Description The lattice-Boltzmann simulation package for soft matter and complex fluid 'Ludwig' is developed in a longterm collaboration between the School of Physics, University of Edinburgh and the Edinburgh Parallel Computing Centre. 
Type Of Technology Software 
Year Produced 2016 
Open Source License? Yes  
Impact New improvements in the electrokinetic and liquid-crystalline functionalities have been implemented and were released. The user base has been extended and includes now new researchers at the University of Cambridge and Oxford, who will be using Ludwig for their research. 
URL http://ludwig.epcc.ed.ac.uk
 
Description Public Engagement with Sutton Trust 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact An introduction into computational physics was given to about 30 secondary class pupils who visited the University of Edinburgh. This activity was initiated by the Sutton Trust, a charitable organisation which has the goal to improve social mobility through education. The students were very motivated and requested source code that was used in the interactive demonstration of epidemiological models. The feedback for this activity was throughout very positive.
Year(s) Of Engagement Activity 2016
 
Description oxDNA Webinar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact An extended webinar outlining the oxDNA user-package was broadcasted to the ARCHER user community. The webinar was recorded and is available for future reference. Members of the scientific community are showing interest in this functionality and the world-wide user community of the LAMMPS code, on which this package is based, will facilitate its dissemination.
Year(s) Of Engagement Activity 2016