The melding of immunodynamics, epidemiology and evolutionary biology to explore how pathogen genetic variation is modulated by host immunity, transmission bottlenecks and epidemic dynamics to determine the wide range of pathogen phylogenies observed at scales from individual host to population.
A blend of expertise in many different disciplines is required to investigate pathogen phylodynamics effectively. CIDD brings together researchers with backgrounds in a wide range of highly relevant fields — from phylogenetics and immunology to epidemiological modeling.
RNA virus phylodynamics
Mutation, recombination, reassortment and gene rearrangement can all generate variability in RNA virus genomes. This variability is acted on by selection, particularly:
- Within hosts: for instance, the host immune system eliminates some viral genotypes.
- During transmission: a pathogen's ability to infect new hosts depends on intrinsic characteristics of pathogen and host (such as the pathogen's ability to withstand dessication, if it is transmitted by aerosol), and also on extrinsic variables such as the spatial distribution of host populations (for example, this can affect the time needed to find a new host).
The high mutation rates and short generation times of RNA viruses allow us to explore evolution on relatively short timescales. We are examining what characteristics of viral genomes enable them to survive within hosts and get transmitted under different circumstances.
A key issue: quantifying pathogen variability
We are empirically quantifying levels of variability in RNA viral populations — at different spatial and temporal scales — in order to identify major selection processes and their effects. For instance, we are measuring variability:
- Within hosts: in naive hosts and in hosts with various histories of exposure to related and unrelated pathogens
- Pre- and post-transmission: how pathogen variability changes during transmission from one host to the next; what characteristics enable or hamper transmission under different circumstances
We are extending these ideas to systems other than RNA viruses. In particular, we are quantifying changes in variability in the bacterium Bordetella bronchiseptica during transmission between hosts (mice).
Importance for control strategies
Phylodynamic studies will allow us to tease out the biological mechanisms underlying the observed evolution of pathogen species. Understanding these is crucial to devising effective control strategies for important human and animal diseases, including emerging zoonotic and other diseases.
For instance, the formulation of influenza vaccines before each 'flu season is essentially a process of evolutionary prediction. A phylodynamic understanding of how influenza evolution works — at host and population levels — is highly relevant to this procedure.