Tag Archives: population

Modelling from the cell through the individual to the host population

During the lock-down in the UK due to the coronavirus pandemic, I have been reading about viruses and the modelling of them.  It is a multi-disciplinary and multi-scale problem; so, something that engineers should be well-equipped to tackle.  It is a multi-scale because we need to understand the spread of the virus in the human population so that we can control it, we need to understand the process of infection in individuals so that we can protect them, and we need to understand the mechanisms of virus-cell interaction so that we can stop the replication of the virus.  At each size scale, models capable of representing the real-world processes will help us explore different approaches to arresting the progress of the virus and will need to be calibrated and validated against measurements.  This can be represented in the sort of model-test pyramid shown in the top graphic that has been used in the aerospace industry [1-2] for many years [see ‘Hierarchical modelling in engineering and biology’ on March 14th, 2018] and which we have recently introduced in the nuclear fission [3] and fusion [4] industries [see ‘Thought leadership in fusion engineering’ on October 9th, 2019].  At the top of the pyramid, the spread of the virus in the population is being modelled by epidemiologists, such as Professor Neil Ferguson [5], using statistical models based on infection data.  However, I am more interested in the bottom of the pyramid because the particles of the coronavirus are about the same size as the nanoparticles that I have been studying for some years [see ‘Slow moving nanoparticles’ on December 13th, 2017] and their motion appears to be dominated by diffusion processes [see ‘Salt increases nanoparticle diffusion’ on April 22nd, 2020] [6-7].  The first step towards virus infection of a cell is diffusion of the virus towards the cell which is believed to be a relatively slow process and hence a good model of diffusion would assist in designing drugs that could arrest or decelerate infection of cells [8].  Many types of virus on entering the cell make their way to the nucleus where they replicate causing the cell to die, afterwhich the virus progeny are dispersed to repeat the process.  You can see part of this sequence for coronavirus (SARS-COV-2) in this sequence of images. The trafficking across the cytoplasm of the cell to the nucleus can occur in a number of ways including the formation of a capsule or endosome that moves across the cell towards the nuclear membrane where the virus particles leave the endosome and travel through microtubules into the nucleus.  Holcman & Schuss [9] provide a good graphic illustrating these transport mechanisms.  In 2019, Briane et al [10] reviewed models of diffusion of intracellular particles inside living eukaryotic cells, i.e. cells with a nuclear enclosed by a membrane as in all animals.  Intracellular diffusion is believed to be driven by Brownian motion and by motor-proteins including dynein, kinesin and myosin that enable motion through microtubules.  They observed that the density of the structure of cytoplasm, or cytoskeleton, can hinder the free displacement of a particle leading to subdiffusion; while, cytoskeleton elasticity and thermal bending can accelerate it leading to superdiffusion.  These molecular and cellular interactions are happening at disparate spatial and temporal scales [11] which is one of the difficulties encountered in creating predictive simulations of virus-cell interactions.  In other words, the bottom layers of the model-test pyramid appear to be constructed from many more strata when you start to look more closely.  And, you need to add a time dimension to it.  Prior to the coronavirus pandemic, more modelling efforts were perhaps focussed on understanding the process of infection by Human Immunodeficiency Virus (HIV), including by a multi-national group of scientists from Chile, France, Morocco, Russia and Spain [12-14].  However, the current coronavirus pandemic is galvanising researchers who are starting to think about novel ways of building multiscale models that encourage multidisciplinary collaboration by dispersed groups, [e.g. 15].

References

[1] Harris GL, Computer models, laboratory simulators, and test ranges: meeting the challenge of estimating tactical force effectiveness in the 1980’s, US Army Command and General Staff College, May 1979.

[2] Trevisani DA & Sisti AF, Air Force hierarchy of models: a look inside the great pyramid, Proc. SPIE 4026, Enabling Technology for Simulation Science IV, 23 June 2000.

[3] Patterson EA, Taylor RJ & Bankhead M, A framework for an integrated nuclear digital environment, Progress in Nuclear Energy, 87:97-103, 2016.

[4] Patterson EA, Purdie S, Taylor RJ & Waldon C, An integrated digital framework for the design, build and operation of fusion power plants, Royal Society Open Science, 6(10):181847, 2019.

[5] Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker C, Imai N, Cuomo-Dannenburg G, Thompson H, Walker PGT, Fu H, Dighe A, Griffin JT, Baguelin M, Bhatia S, Boonyasiri A, Cori A, Cucunubá Z, FitzJohn R, Gaythorpe K, Green W, Hamlet A, Hinsley W, Laydon D, Nedjati-Gilani G, Riley S, van Elsland S, Volz E, Wang H, Wang Y, Xi X, Donnelly CA, Ghani AC, Ferguson NM, Estimates of the severity of coronavirus disease 2019: a model-based analysis., Lancet Infectious Diseases, 2020.

[6] Coglitore D, Edwardson SP, Macko P, Patterson EA, Whelan MP, Transition from fractional to classical Stokes-Einstein behaviour in simple fluids, Royal Society Open Science, 4:170507, 2017.

[7] Giorgi F, Coglitore D, Curran JM, Gilliland D, Macko P, Whelan M, Worth A & Patterson EA, The influence of inter-particle forces on diffusion at the nanoscale, Scientific Reports, 9:12689, 2019.

[8] Gilbert P-A, Kamen A, Bernier A & Garner A, A simple macroscopic model for the diffusion and adsorption kinetics of r-Adenovirus, Biotechnology & Bioengineering, 98(1):239-251,2007.

[9] Holcman D & Schuss Z, Modeling the early steps of viral infection in cells, Chapter 9 in Stochastic Narrow Escape in Molecular and Cellular Biology, New York: Springer Science+Business Media, 2015.

[10] Braine V, Vimond M & Kervrann C, An overview of diffusion models for intracellular dynamics analysis, Briefings in Bioinformatics, Oxford University Press, pp.1-15, 2019.

[11] Holcman D & Schuss Z, Time scale of diffusion in molecular and cellular biology, J. Physics A: Mathematical and Theoretical, 47:173001, 2014.

[12] Bocharov G, Chereshnev V, Gainov I, Bazhun S, Bachmetyev B, Argilaguet J, Martinez J & Meyerhans A, Human immunodeficiency virus infection: from biological observations to mechanistic mathematical modelling, Math. Model. Nat. Phenom., 7(5):78-104, 2012.

[13] Bocharov G, Meyerhans A, Bessonov N, Trofimchuk S & Volpert V, Spatiotemporal dynamics of virus infection spreading in tissues, PLOS One, 11(12):e)168576, 2016.

[14] Bouchnita A, Bocharov G, Meyerhans A & Volpert V, Towards a multiscale model of acute HIV infection, Computation, 5(6):5010006, 2017.

[15] Sego TJ, Aponte-Serrano JO, Ferrari-Gianlupi J, Heaps S, Quardokus EM & Glazier JA, A modular framework for multiscale spatial modeling of viral infection and immune respons in epithelial tissue, bioRxiv. 2020.

Citizens of the world

Last week in Liverpool, we hosted a series of symposia for participants in a dual PhD programme involving the University of Liverpool and National Tsing Hua University, in Taiwan, that has been operating for nearly a decade.  On the first day, we brought together about dozen staff from each university, who had not met before, and asked them to present overviews of their research and explore possible collaborations using as a theme: UN Sustainable Development Goal No.11: Sustainable Cities and Communities.  The expertise of the group included biology, computer science, chemistry, economics, engineering, materials science and physics; so, we had wide-ranging discussions.  On the second and third day, we connected a classroom on each campus using a video conferencing system and the two dozen PhD students in the dual programme presented updates on their research from whichever campus they are currently resident.  Each student has a supervisor in each university and divides their time between the two universities exploiting the expertise and facilities in the two institutions.

The range of topics covered in the student presentations was probably even wider than on the first day; extending from deep neural networks, through nuclear reactor technology, battery design and three-dimensional cell culturing to policy impacts on households.  One student spoke about the beauty of mathematical equations she is working on that describe the propagation of waves in lattice structures; while, another told us about his investigation of the causes of declining fertility rates across the world.  Data from the UN DESA Population Division show that live births per woman in the Americas & Europe have already fallen below the 2.1 required to sustain the population, while it is projected to fall below this level in south-east Asia within the next five years and in the world by 2060.  This made me think that perhaps the Gaia principle, proposed by James Lovelock, is operating and that human population is self-regulating as it interacts with constraints imposed by the Earth though perhaps not in a fashion originally envisaged.

 

Engineering correspondents needed

Society’s perception  of scientists and engineers is not well-balanced; scientists tend to get the headlines when they make new discoveries while engineers are only in the headlines when things go wrong.  Even worse, when I was a student, the successes of the NASA’s space shuttle were usually reported as scientific achievements while its problems were engineering failures; when the whole programme was an enormous feat of engineering!  Perhaps this is because news organisations tend to have science correspondents and editors but no engineering correspondents.  When you search for engineering journalism jobs most of the results relate to roles associated with the technology of journalism; whereas a search for science journalism jobs results in dozens of vacancies for science writers, correspondents and editors.  The lack of engineering correspondents has been evident in the UK during the past week in reporting about the potential bursting of the dam at Toddbrock Reservoir and flooding of the town of Whaley Bridge in Derbyshire UK.  A 188 year old dam has been damaged by the turbulent flow of water over its spillway following unprecedented levels of rainfall (e.g. https://www.bbc.co.uk/news/uk-england-derbyshire-49222956). There is little discussion of the significant achievement of the Victorian engineers who designed and built a dam in the 1831 that has lasted 188 years or that climate change is causing shifts in weather patterns which have altered the design specifications for engineering infrastructure including dams, bridges and sea defences.  We need more journalists to write about engineering and preferable more journalists who have been educated as engineers particularly as society starts to face the potential existential threat caused by climate change and over-population.

For more on the nature of engineering, and its relationship to science, see ‘Making things happen‘ on September 26th, 2018; ‘Engineering is all about ingenuity‘ on September 14th, 2016 and ‘Life takes engineering‘ on April 22nd 2015.

And on the communication skills of engineers: ‘Poetasting engineers‘ on March 4th, 2015 and ‘Einstein and public engagement‘ on August 8th, 2018.

Planetary Emergency

Global energy budget from Trenberth et al 2009

This week’s lecture in my thermodynamics course for first-year undergraduate students was about thermodynamic systems and the energy flows in and out of them. I concluded the lecture by talking about our planet as a thermodynamic system using the classic schematic in the thumbnail [see ‘Ample sufficiency of solar energy‘ on October 25th, 2017 for more discussion on this schematic].  This is usually a popular lecture but this year it had particular resonance because of the widely publicised strikes by students for action on climate change.  I have called before for individuals to take responsibility given the intransigence of governments [see ‘Are we all free riders‘ on June 6th, 2016 or ‘New Year Resolution‘ on December 31st, 2014]; so, it is good to see young people making their views and feelings known.

Weather-related events, such as widespread flooding and fires, are reported so frequently in the media that perhaps we have started to ignore them as portents of climate change.  For me, three headlines events have reinforced the gravity of the situation:

  1. The publication earlier this month of a joint report by UNICEF and the Royal College of Paediatrics and Child Health that air pollution in the UK so high that it is infringing the fundamental rights of children to grow up in a clean and safe environment; and, under the Government’s current plans, air pollution in the UK is expected to remain at dangerous levels for at least another 10 years.
  2. The warning earlier this month from the Meteorological Office in London that global warming could exceed 1.5C above pre-industrial levels within five years.  In my lecture, I highlighted that a 2C rise would be equal to the temperature 3 million years ago when sea levels were 25 to 35m high; and, a 1m rise in sea level would displace 145 million people globally [according to Blockstein & Weigmann, 2010].
  3. The suspension of construction of the new nuclear power station on Anglesey by Hitachi, which leaves the UK Government’s energy strategy in disarray with only one of the six planned new power stations under construction.  This leaves the UK unable to switch from fossil-fuelled to electric vehicles and dependent on fossil fuel to meet current electricity demand.

I apologise for my UK focus this week but whereever you are reading this blog you could probably find similar headlines in your region.  For instance, the 2016 UNICEF report states that one in seven children worldwide live in toxic air and air pollution is a major contributing factor in the deaths of around 600,000 children under five every year.  These three headlines illustrate that there is a planetary emergency because climate change is rapidly and radically altering the ecosystem with likely dire consequences for all living things; that despite a near-existential threat to the next generation as a consequence of air pollution most governments are effectively doing nothing; and that in the UK we are locked into a fossil-fuel dependency for the foreseeable future due to a lack of competent planning and commitment from the government which will compound the air pollution and climate change problems.

Our politicians need to stop arguing about borders and starting worrying about the whole planet.  We are all in this together and no man-made border will protect us from the impact of making the planet a hostile environment for life.