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The ecology within: health implications of within-host ecology

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Title: The ecology within: health implications of within-host ecology
Author: Murall, Carmen Lia
Department: Department of Integrative Biology
Program: Integrative Biology
Advisor: Bauch, ChrisMcCann, Kevin
Abstract: Many of the medical problems that continue to elude us involve complex networks of interacting cells, biochemicals, and microorganisms. These within-host dynamical systems constitute the ecology that happens inside of us, and we are only beginning to explore these systems as ecological systems. In this thesis, I investigate how untangling these webs of interactions and their corresponding dynamics can help us mechanistically understand many diseases, particularly those caused by infections. I address how to further apply ecological theory to within-host systems and demonstrate how deeper ecological understanding of an infection can reveal unexpected behaviours that may hinder the long-term effectiveness of the vaccines we develop to combat such infections. I begin by proposing that some lessons from ecology, specifically from community ecology, have not been fully harnessed in our studies of the dynamics of infections. For instance, within-host trade-offs are poorly understood and rarely sought after empirically. And yet, with a simple mathematical model of viral dynamics I showed that within-host trade-offs strongly determine the outcomes of chronic and acute infections. For instance, I showed how simple human behaviours that affect immunity, like smoking, can alter these within-host trade-offs and favour infections dominated by more virulent strains. Unfortunately, studies to identify what evolutionary and ecological processes shape infectious diseases are not usually undertaken before we develop control methods against them. I consider the specific example of Human Papillomavirus (HPV), where discussions about the ecology and evolution of HPV types did not seriously begin until after the launch of a new type-specific vaccine. After developing novel viral dynamics model of HPV co-infections that incorporated the essential patchiness of lesion dynamics, I investigated competing hypotheses of HPV type interactions. I found that ‘neutral’ interactions, the prevailing assumption in the literature, do not best explain the (limited) within-host co-infection data that we have. This suggests that neutrality between HPV types could be a fallacy, and the consequence could be that the vaccine is releasing types not targeted by the vaccine from competitive pressures. Similarly, with another within-host model I found that the vaccine within-host environment also releases HPV from important selection pressures which could consequently allow the virulence level of HPV to increase. I demonstrate, then, that understanding ecological conditions inside hosts allows us to make predictions about the potential evolutionary responses of pathogens against control methods such as vaccines. Overall, this dissertation highlights that more studies into the ecology happening within the body are needed in order to improve our confidence in the long-term successes of our medical strategies.
Date: 2013-08
Rights: Attribution-NonCommercial-NoDerivs 2.5 Canada
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Attribution-NonCommercial-NoDerivs 2.5 Canada Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 2.5 Canada