In partial fulfillment of the requirements for the degree of

Doctor of Philosophy in Biology

In the

School of Biological Sciences

Tim O’Sullivan

Will defend his dissertation

The Dynamics of death:

determining the relationship between within-host pathogen dynamics and host mortality

Tuesday, August 11th, 2020

1:00 PM

https://bluejeans.com/373440017/

Meeting ID: 373 440 017

 Thesis Advisor:

Dr. Sam Brown

School of Biological Sciences

Georgia Institute of Technology

Co-Advisor:

Dr. Kristofer Wollein Waldetoft

School of Biological Sciences

Georgia Institute of Technology

Committee Members:

Dr. Patrick McGrath

School of Biological Sciences

Georgia Institute of Technology

Dr. Steve Diggle

School of Biological Sciences

Georgia Institute of Technology

Dr. Nicole Vega

Department of Biology

Emory University

ABSTRACT

Infectious diseases remain a major cause of global mortality, yet basic questions concerning the relationship between within-host pathogen processes and epidemiological patterns of mortality remain obscure. First, I develop a conceptual framework to link pathogen dynamics (pathogen burden p(t) as a function of time since infection t) with instantaneous host mortality m(t), and show that multiple math models are consistent with observed accelerating m(t) infection data, using existing data from multiple experimental infection models.  Second,  I develop an experimental C. elegans / Pseudomonas aeruginosa infection model platform to allow non-invasive tracking of p(t), along with time of death t* and population-scale mortality m(t) across a cohort of infected animals, including a novel bioinformatic methodology for analysis. Finally, I link my conceptual questions to empirical data gathered with my developed platform. Using a 46 worm cohort, I show that that pathogen burden p(t) is a weakly declining function of time since infection in the majority of individual worms, and across worms the estimated instantaneous risk of death m(t) accelerates in time. These results are not consistent with models where pathogen expansion is the cause of death, and indicate instead that initial high (and lethal) pathogen gut inocula are being partially cleared. This work offers a high throughput platform to link within-host pathogen dynamics to epidemiological parameters using a robust, genetically tractable host / pathogen system.