Joshua Weitz (Week 4): Viral Strategies and Dynamics from Lysis to Latency
Objective: Viral infections can lead to the lysis of microbes and the release of organic matter back into the environment. This organic matter can then be taken up by other organisms, promoting new growth (e.g., by heterotrophic bacteria). Yet, not all viral infections end in lysis. Temperate bacteriophage can integrate their genomes into the chromosome of the bacterial host forming a lysogen. The integrated phage genome (or ‘prophage’) can be stably passed from mother to daughter cells. Over time, the prophage can also induce, reinitiating the lytic pathway, leading to the lysis of the bacterial host and the release of virions back into the environment. Notably, both the ‘decision’ to lyse or integrate upon infection and the ‘decision’ to induce from the lysogenic state are modulated by viral, cellular, and environmental factors. The aim of this short course is to develop a foundational theoretical framework as well as practical computational skills to analyze such decisions in a dynamical systems context. To do so, the short course will provide students with the necessary ecological, theoretical, and computational foundations to explore problems independently. The course will include background information on nonlinear dynamical systems, local stability analysis, invasion analysis, as well as core computational methods for analyzing the joint dynamics of viruses and their microbial hosts. Students are expected to work independently or in small groups to analyze how the invasion fitness of viral strategies depends on ecological context and how distinct viral strategies interact.
Course Schedule
Principles and Introduction: Monday-Tuesday
The central goal will be to introduce the broad ecological principles underlying the short course and the necessary mathematical and computational toolkits to assess the question of the adaptive benefits of viral strategies in a dynamical (eco-evolutionary) systems context.
Monday August 9, 8am-9:30am Pacific – The Entangled Fates of Viruses and Their Microbial Hosts (public lecture; targeted to both course participants and general workshop audience)
Tuesday August 10, 8am-9:30am Pacific –Tutorial on ‘Local stability, thresholds, and viral invasion fitness’ (interactive, targeted to course participants)
Independent Work Focus: Wed-Friday
Independent work will focus on an interwoven set of problems: (i) assess adaptive benefits of viral strategies by calculating the basic reproduction number and growth rates of distinct viral strategies across a continuum from lysis to latency as a function of environmental state; (ii) explore how links between resource availability and growth rate can impact viral invasion; (iii) evaluate the interactions between virulent and temperate strategies in a community context, given protective benefits of immunity. Coding support will be provided primarily in Matlab and Python via the Office Hours.
Wednesday August 11, Office Hours (Drs. Demory and Harris, Georgia Tech ~1.5 hrs)
Thursday August 12, Office Hours (Drs. Demory and Harris, Georgia Tech ~1.5 hrs)
Friday August 13, 8am-9:30am Pacific – Presentations by students on findings
Reading (from JSW group + collaborators)
1. Correa, A.M.S., Buchan A., Sullivan, M.B., and Weitz, J.S. (2021). Rules of life for viruses of microorganisms. Nat. Reviews Microbiology
2. Li, G., Cortez, M.H. and Weitz, J.S. (2020) When to be temperate: on the benefits of lysogeny vs. lysis, Virus Evolution
3. Weitz, J.S., #Li, G., Gulbudak, H., Cortez, M.H., and Whitaker, R.J. (2019) Viral invasion fitness across a continuum from lysis to latency. Virus Evolution. 5: vez006
Additional Key Readings
1. Wahl, L.M. et al. (2019) Evolutionary stability of the lysis-lysogeny decision: why be virulent? Evolution
2. Berngruber, T.W. et al., (2013) Evolution of virulence in emerging epidemics. PLoS Pathogens.
________________________________________________________________________________
Tami Lieberman and Shijie Zhao (Week 5): Adaptive Evolution within Gut Microbiomes.
https://www.sciencedirect.com/science/article/pii/S1931312819301593
Monday Lecture:
- Paper presentation & discussion
- SNP calling: Examples of real and artifactual calls and their causes
- Tree building and dating
Monday assignment
- Try to figure out filter parameters to call SNPs
- Try to build a tree with calls
- Bonus: Try to infer molecular clock
Tuesday Lecture
- Teach how you would identify recombination
- Introduce evolutionary theory about ancestral allele
- Show them how to play with figtree
- Typical tree problems
- Teach molecular clock, why you might need to normalize for coverage
- More about tree building
- What mutations are considered the same and why (A->G = T->C)
Tuesday assignment
- Continue tree building and clock from yesterday
- Use outgroups to infer ancestral allele and improve clock
- Mutational spectrum of L08 hypermutator
Weds - independent study
Thursday Lecture
- Parallel evolution
- Signature for selection
- dN/dS in theory
- Mechanics of how dN/dS is calculated in practice
Thursday assignment
- Search for parallel evolution
- Build null models for parallel evolution
- Easy thing first: N/S whole genome vs genes under selection (no model)
- Calculate dN/dS
Friday Lecture
- Review results, discussion
- Gain and loss analysis
- List some outstanding questions for future exploration
Friday assignment
- Optional: Do gain and loss analyses