Seminar Physics of viruses
This interdisciplinary seminar addressed advanced bachelor and master students from physics and biology. It is jointly organized by Ulrich Schwarz (ITP and BioQuant) and Frederik Graw (BioQuant). Due to the corona crisis, it will be conducted as virtual block seminar. We will discuss the distribution of talks and dates for your meetings in a first introductory meeting on Wednesday April 22 2020, 4 pm. For more administrative details, see below.
Viruses have always fascinated physicists and the history of virology is full of important contributions by physicists. For example, Francis Crick (a theoretical physicist) together with Jim Watson first suggested that virus capsids must be made from only one or a few identical proteins (Nature paper 1956), a prediction that later was verified e.g. by Aaaron Klug (also a physicist) using electron microscopy and X-ray diffraction (Nobel prize 1982). Today structure determination by physical methods is daily routine when investigating the molecular structure of viruses. In the current corona crisis, the first steps of analysis were sequencing of the SARS-CoV-2 genome and structural characterization of its surface spike proteins.
Another important physical aspect is quantification of experiments with viruses, which often is easier than for other more complex biological systems. The most impressive historical evidence in this direction is the work of Max Delbrück, by training a theoretical physicist, who was inspired by the work of Erwin Schrödinger and around 1940 started the famous phage group at Cold Spring Harbor Laboratory in the USA, together with the geneticist Salvador Luria. Their quantitative experiments on bacteriophages (viruses attacking bacteria) lead to an understanding of the decisive steps in virus replication and later earned them the Nobel prize. Today we have a fairly good understanding of the different steps in the life of many viruses inside their host cells, including uptake, transport, replication, assembly and exit. For all of these steps mathematical models exist that capture their essential physical aspects. What is much less understood, however, is how viruses spread between host cells, because this depends on many extracellular factors.
Spreading of viruses becomes more amendable to mathematical analysis if we consider it on the population level, where many details average out. This is evidenced by the huge success of the SIR-model (kinetic model with classes Susceptible, Infectious and Recovered). First analyzed by Kermack and McKendrick in 1927, the SIR-model and related kinetic models describe the typical time course of an infection (initially exponential growth, then peak and finally decline). The SIR-model has been extended and modified in many ways, including seasonal forcing, stochastic effects, age structure, the role of space and the spread on networks. In the current corona crisis, it has been used many times to predict the future course of the pandemics and the effect of possible control strategies (in particular social distancing). It also has been used to prove that the interventions in Germany on March 6 and 16 did in fact constitute change points in the spreading dynamics.
Because viruses are essentially genomes wrapped by some protective coat, they are ideal systems to study genetics, in particular the dynamics of mutuations. Historically, the study of viruses was essential to decipher the genetic code and the difference between DNA and RNA. Today we need to understand their mutation dynamics to predict their evolution and to develop vaccines (most prominently for the annual influenza wave during winter; many viruses have seasonal variation, but the exact reasons for this are not always clear).
In this seminar, we will discuss the current state of the art regarding our quantitative understanding of viruses. This includes all the aspects described above, including their structure and assembly, uptake and exit processes, spreading in the extracellular environment, spreading on the population level (especially on aviation and social contact networks) and their evolutionary dynamics. The later subjects are especially important to develop mitigation strategies and forecasting.
Given the current situation, we will also discuss SARS-CoV-2, but here one has to be careful for several reasons. First we do not yet know much about it and our main knowledge comes from SARS-CoV (the virus responsible for the SARS-outbreak in 2002/2003). Second SARS-CoV-2 virus is not the most typical virus (very large RNA-genome, virus capsid not really characterized yet, very large corona surrounding the particle, entry pathway might depend on host cell type) and many aspects of the associated disease COVID-19 are not really understood yet (individual susceptibility of patients is very variable, strong impact on the elderly, affects multiple organs, seasonal dependance unclear, role of children for transmission also unclear). In general, this seminar is concerned with the generic physical aspects of viruses and less with one specific virus like SARS-CoV-2. Due to the background and own work by the organizers, we will in particular discuss HIV and influenza, which are very strong research subjects at Heidelberg (also in the context of SFB 1129 on quantitative analysis of pathogen replication and spread).
To participate, you had to register through the physics teaching database. We are sorry to say that due to the strong demand, registration had to be closed already after one day. Our meetings will be conducted on zoom. Please install the zoom app ahead of the meeting (free version sufficient). During our first meeting on Wednesday April 22 2020 4 pm, participants can choose their topic from a prepared list with literature. Typically two participants together will give a 30 min talk and answer questions during a 15 min discussion. We will have one block on May 18 and 19 on the structure of viruses, and one block on June 22 and 23 on spreading of viruses.
For physics bachelor students, participation and talk give two credit points. This will be counted as obligatory seminar for bachelor students (PSEM) and a mark will be reported for your transcript. For physics master students, you can get six credit points and a mark for an obligatory master seminar (MVSem), but for this you also have to hand in a 15-20 pages written paper on your subject after the seminar is finished (typically within 1-2 months). Everybody is welcome to ask questions to the organizers when preparing the presentation, possibly during one-on-one virtual meetings.
Material by the organizers
Recommended background reading
- Rob Philipps, Jane Kondev and Julie Theriot, Physical biology of the cell, 2nd edition, Taylor and Francis 2012
- Bruce Alberts et al., Molecular Biology of the Cell, 6th edition 2014
- David M. Knipe and Peter M. Howley, Fields virology, 6th edition 2013
- Matt J Keeling and Pejman Rohani, Modeling infectious diseases in humans and animals, Princeton University Press 2008
- Hakan Andersson and Tom Britton, Stochastic Epidemic Models and their Statistical Analysis by Hakan Andersson and Tom Britton, Springer 2000
- Theoretical biophysics script (PDF) by Ulrich Schwarz
- Kumberger, Peter, et al. "Multiscale modeling of virus replication and spread." FEBS letters 590.13 (2016): 1972-1986.
- Perelson, Alan S. "Modelling viral and immune system dynamics." Nature Reviews Immunology 2.1 (2002): 28-36.
- Zlotnick, Adam. "Theoretical aspects of virus capsid assembly." Journal of Molecular Recognition: An Interdisciplinary Journal 18.6 (2005): 479-490.
- Roos, W. H., R. Bruinsma, and G. J. L. Wuite. "Physical virology." Nature physics 6.10 (2010): 733-743.
- Zhang, Sulin, Huajian Gao, and Gang Bao. "Physical principles of nanoparticle cellular endocytosis." ACS nano 9.9 (2015): 8655-8671.
- Hagan, Michael F. "Modeling viral capsid assembly." Advances in chemical physics 155 (2014): 1.
- Perlmutter, Jason D., and Michael F. Hagan. "Mechanisms of virus assembly." Annual review of physical chemistry 66 (2015): 217-239.
- Bar-On, Yinon M., et al. "Science Forum: SARS-CoV-2 (COVID-19) by the numbers." Elife 9 (2020): e57309.
Websites related to SARS-CoV-2
- Johns Hopkins University Dashboard https://arcg.is/0fHmTX
- Worldometer https://www.worldometers.info/coronavirus/
- Dirk Brockmann, HU Berlin http://rocs.hu-berlin.de/corona/docs/forecast/results_by_country/
- Richard Neher, Basel https://covid19-scenarios.org
- Nextstrain https://nextstrain.org
- CMMID London https://epiforecasts.io/covid/posts/global/
- Data against covid https://www.data-against-covid.org
- Data on masks https://www.n95decon.org
- Covid-19 website by Deep Knowledge group https://www.dkv.global/covid
- Covid-19 modelling website by David Odde at Minnesota https://iem-covid19.com