Ruprecht Karls Universität Heidelberg

Seminar Physics of viruses

This interdisciplinary seminar addressed advanced bachelor and master students from physics and biology. It is jointly organized by Ulrich Schwarz and Falko Ziebert (ITP) and Frederik Graw (BioQuant). Due to the corona crisis, it will be conducted as virtual block seminar. Our four block will be the mornings of June 21 and 28, and the afternoons of June 25 and July 2 2021, as discussed during our preparatory meeting on April 14 2021.

Scientific scope

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. Interestingly, X-ray diffraction today is less important than it used to be, being more and more replaced by cryo electron microscopy (Nobel Prize Chemistry 2017).

Another important physical aspect is quantification of virus dynamics, 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). And of course it is used to estimate the daily R-number from measured data (nowcasting).

Because viruses are essentially genomes wrapped by some protective coat, they are ideal systems to study genetics, in particular the dynamics of mutations. 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, in particular against new variants which invariably emerge if many people are being infected. Phylogenetics as exemplified by the nextstrain database allows us to follow how viruses spread, to predict future developments and to design mitigation strategies.

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 and their evolutionary dynamics.

Given the current situation, we will of course also discuss SARS-CoV-2, which shares some similarities with Ebola, Influenza and HIV viruses, which are also enveloped RNA-viruses. We will also discuss that progress on SARS-CoV-2 has been fast also because we already know so much about SARS-CoV and MERS-CoV. All of these viruses are under current investigation at Heidelberg. In general, however, this seminar is concerned with the generic physical aspects of viruses and less with one specific virus like SARS-CoV-2.

Administration

To participate, you had to register through the physics teaching database. 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 14 2021 at 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.

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 (deadline September 30, extension possible upon request). Everybody is welcome to ask questions to the organizers when preparing the presentation, possibly during one-on-one virtual meetings.

List of subjects and schedule

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

Some helpful reviews

  • Roos, W. H., R. Bruinsma, and G. J. L. Wuite. "Physical virology." Nature physics 6.10 (2010): 733-743.
  • Bruinsma, Robijn F., Gijs JL Wuite, and Wouter H. Roos. "Physics of viral dynamics." Nature Reviews Physics 3.2 (2021): 76-91.
  • 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.
  • Petrova, Velislava N., and Colin A. Russell. "The evolution of seasonal influenza viruses." Nature Reviews Microbiology 16.1 (2018): 47-60.
  • Zlotnick, Adam. "Theoretical aspects of virus capsid assembly." Journal of Molecular Recognition: An Interdisciplinary Journal 18.6 (2005): 479-490.
  • 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.
  • Yinon M. Bar-On, Ron Sender, Avi I. Flamholz, Rob Phillips, Ron Milo, "Quantitative clarification of key questions about COVID-19 epidemiology", https://arxiv.org/abs/2007.05362.