YY-EEID US-UK XXXX: Eco-Evolutionary dynamics of infectious diseases in host population networks.

Lead Research Organisation: Cardiff University
Department Name: School of Biosciences

Abstract

Natural host populations are often fragmented, consisting of several small populations that are linked to one another by animal movement. Fragmented population structures may occur naturally, due to patchy distributions of suitable habitat, or result from human activity and transformations of the landscape. Understanding how changes in population network topology (e.g. size and degree of connectivity between populations) affects disease transmission is an urgent priority, because we are continuously, though often inadvertently, changing network topology. This is particularly important when we consider the transmission of infections across hosts in these networks. Our proposed work will combine data collected from wild desert bighorn sheep (DBH) with new theoretical approaches (e.g. network models) to investigate how infection risks change in populations with different levels of fragmentation. Further, because the kinds of infections animals have will, over evolutionary time, alter the types of infection they are able to respond to, we will also determine how network topology affects the genetic adaptation of immune defense. This is particularly important because, the immune responses in host populations will affect that populations' vulnerability to emerging infectious diseases and so animals in different networks are likely to have different abilities to resist new 'emerging' infections.
We propose that the level of connectivity and animal movement between populations will change which parasites and microbes are able to persist within each network. Further, as more than one species of parasite can infect an animal and these parasite species can often interact, we propose that the structure of the parasite community in individual hosts will then be driven by these. To investigae our hypotheses, we will take faecal samples from sheep followed over extended periods, to uncover the landscape-level parasite community patterns in desert bighorns across three differently fragmented populations. Then focusing in on the well-studied network from the Mojave desert, we will combine these longitudinal observational data with experimental approaches to determine how parasite interactions structure the within-host parasite communities. We will also measure immune responses and survey immunogenetic profiles of sheep to estimate how different parasite communities may drive natural selection across 14 bighorn sheep populations. We will then use our empirical data to parameterize and test mathematical network models exploring how ecological and host evolutionary processes shape disease dynamics in bighorns in particular, and across population networks in general. The broad scope and ambitious goals of the proposed work are attainable because reasons: (i) the DBH provid replicate host populations that vary in population connectivity and parasite communities, but are otherwise similar. (ii) We can harness the power of novel molecular techniques to track communities of different groups of parasite. (iii) We will develop innovative modeling approaches, which will integrate our field data on the transmission of microbes and parasites with detailed measured of host immunity. Our modeling framework will allow us to explore both general questions (e.g. How does host population fragmentation impact which parasites persist and spread?) and more tactical concerns (e.g. How will particular changes in landscape connectivity -- e.g. highway construction / animal movement restrictions - affect infection risk?). Host population networks are everywhere - from desert bighorn sheep on mountain tops, to networks of protected areas, through to farms and cities. The proposed study would allow us to develop and test a mathematical framework for exploring ecological and evolutionary dynamics of infectious diseases in different host population networks, potentially transforming how we think about variation in exposure risks among populations over space and time.

Technical Summary

Natural host populations often occur as fragmented metapopulations. Understanding how changes in population network topology affect disease transmission is an increasingly urgent priority, as humans continue to manipulate landscapes and alter connectivity between popoulations.
At ecological time scales, disease transmission in host networks is a balance, between rapid spread throughout the network and the virulence caused in individual hosts. Changes in network topology are likely to shift this balance leading to loss of some parasite species. We hypothesise that network topology will determine the distribution of parasite taxa across the metapopulation, while within-host parasite interactions will structure local parasite communities. At evolutionary time scales, each population's exposure profile - the incidence and types of parasite that occur in the population - will shape host immunogenetic adaptation resulting in differential patterns of vulnerability to infection.
We will study the dynamics of host-associated bacteria, protozoa and helminths (host-associated taxa - HAT) in three bighorn sheep metapopulations with different network topologies asking how does (1) How does network topology structure HAT communities? (2) How does variation among populations in HAT communities drive local immunogenetic adaptation? and (3) How does network topology shape infection risks and disease dynamics? We expect that differences in HAT communities across populations mediate differential selection on immunogenetic loci, resulting in variation in immune responses and local immunogenetic adaptation. Further, we hypothesize that feedbacks between the ecological and evolutionary processes drive the dynamics of HAT communities in host population networks, resulting in differential vulnerability to emerging infections across populations.

Planned Impact

General Public
Emerging diseases threaten human health, food security and conservation efforts, all of which are of interest and importance to the public. Most populations can be considered as metapopulations - i.e. networks connected by animal / human movement and we propose that the structure of these networks alters the capacity of populations to resist infection. Our work will determine how networks topology alters disease resistance and will therefore benefit the public by improving our capacity to undertand and control disease.Desert big horn sheep are an iconic species which are affected by controversial land use issues such as energy installations and open-range grazing of domestic livestock. They therefoe provided a perfect example with which to engage public interest in the research from our work. We will achieve this engagement, through the range of outreach activities explored in the Pathways to Impact Statement.

Agricultural and Public Health Policy Makers.
Emerging infectious disease is one of the most significant threats to human and animal health and welfare, with recent epidemics and pandemics (e.g. ebola, avian influenza, swine flu) highlighting this issue. The vast majority of these infectious diseases (approximately 80%) arise from wildlife reservoirs. Understanding how anthropogenic changes to wildlife metapopulation network structure impacts parasite communities and host immunogenetics is key to understanding risk of emerging infections. This study will allow us to determine what network features promote or defend against novel pathogen invasion. Specifically, we will a) determine whether disrupted wildlife metapopulations networks infer more risk as sources of infection spill-over and b) how restriction in contact networks among human and agricultural populations may influence the risk of those populations to such spill-over.

Wildlife Conservation Policy Makers.
Infectious diseases are a serious and increasing threat to the stability of established wildlife populations and to the recovery of endangered species. While pathogen transmission across networks has been studied before, our study will be the first to explore the role that network topology plays in driving the distribution and structure of whole parasite communities. This work will allow us to ascertain how these structural changes in parasite community influence the likelihood that these different metapopulations resist invasion by an emergent pathogen. This work has direct implications for the endangered study species, Big Horn sheep, which are vulnerable to spill-over of infections from domestic and other animal species (e.g. Mycoplasma from domestic sheep.) In addition, the general principles we explore and that are validated in this host species, can be applied to other vulnerable species existing in metapopulations.

Publications

10 25 50
 
Title Novel immunological and diagnostic macrophage assays. 
Description The team has developed novel immunological and diagnostic macrophage assays for us in the Bighorn sheep project. 
Type Of Material Technology assay or reagent 
Year Produced 2021 
Provided To Others? No  
Impact These assays are still under development but will result in technical publications and will be used by other researchers in the fields of eco-immunology and disease ecology upon their refinement and subsequent publication. 
 
Title Bighorn sheep captures 
Description In November 2020, in collaboration with the California Department of Fish and Wildlife, we participated in the capture of 100 Desert bighorn sheep from 8 Mojave populations and 65 from the Peninsular recovery regions. 
Type Of Material Data handling & control 
Year Produced 2020 
Provided To Others? No  
Impact Using the samples collected at captures, we have run some immune assays to assess the immune responses of individuals. Further analyses will include host genetics and characterization of the microbiome and parasite communities. For the Mojave populations, all 100 animals were fitted with VHF and GPS collars, with 50 of these individuals also receiving rumen internal transmitters (RITs) which monitor metabolic functions (specifically, body temperature and heart rate). 
 
Title Bioinformatic pipeline 
Description The research team previously published a bioinformatics pipeline from samples collected from our Bighorn Sheep study population - the results fo which served as preliminary data for this grant. These previous efforts had quantified some measures of the microbiome community including across subpopulations: relative abundance of key phyla, richness, and diversity. In preparation for the larger dataset that is being collected as part of this grant, Erin Gorsich (University of Warwick) developed statistics to specifically assess parasite/pathogen/microbiome community structure in fragmented host metapopulations. These statistics are commonly applied to ecological communities (often in the absence of phylogenetic information), and can be applied to the larger dataset. Specifically, we explored community nestedness and conducted an indicator species analysis. Nestedness is a measure of how taxa are distributed across hosts and populations, where nested communities indicate that taxa present in hosts/populations with low microbiome richness are subsets of the taxa in hosts or populations with rich microbiomes. The indicator species analyses evaluated if groups of microbiome taxa can be used to predict host population identity. More recently, Gorsich learned methods used for the project's bioinformatics pipeline through coordinating with Tom Sharpton's lab (CoI on grant; Oregon). This included how raw sequence reads are trimmed, filtered, and aligned in the Bioconductor workflow in R as well as the DADA2 method for inferring ribosomal sequence variants (RSV). This is essential to ensure a clear understanding of how the data collection methodology informs inference on community composition. 
Type Of Material Data handling & control 
Year Produced 2020 
Provided To Others? No  
Impact The further development of this process is essential to ensure a clear understanding of how the data collection methodology informs inference on community composition. 
 
Title Longitudinal study 
Description Three intensive 2-month (60 days) field sampling sessions. These sampling sessions occurred in February-March, June-July, and Oct-Nov. Each individual animal was tracked and a non-invasive fecal sample collected approximately every 20 days (3 samples per 60 day period). Samples were collected as soon as possible after being deposited and stored on dry ice until being transferred to -80C storage facilities at Oregon State University. This method preserves the integrity of the fecal sample for downstream microbiome and parasite community analyses. 
Type Of Material Data handling & control 
Year Produced 2021 
Provided To Others? No  
Impact Availability of data for parasitome, microbiome, animal movement and immunological analyses. 
 
Title Preliminary Gut Macroparasite Data 
Description A preliminary gut helminth dataset, collated by a post-graduate student (Oregon State) from a limited number of big horn sheep faecal samples collected from one of our study communities, prior to Covid disruptions. 
Type Of Material Data handling & control 
Year Produced 2020 
Provided To Others? No  
Impact This simple first step has provided a broad picture of the parasite diversity and abundance, as measured by egg counts using standard faecal floatation and microscopy techniques. 
 
Title Preliminary sheep ID parasitome and microbiome analysis 
Description We submitted 244 of our samples collected as part of the Peninsular region cross-sectional study for genotyping, with 160 individuals being identified from these. In addition, based on some of Mojave capture and Peninsula samples, initial microbiome and parasite community analyses were conducted to establish whether our choice of DNA extraction method would significantly affect our downstream results. 
Type Of Material Data handling & control 
Year Produced 2021 
Provided To Others? No  
Impact The findings from these analyses were that our preferred method, using robotic extractions, did not differ significantly from more conventional extraction methods, and will be our employed method in future analyses. We have also developed novel immunological assays to assess the function of macrophages and lymphocytes in bighorn sheep, which we tested during the captures in November 2020. We have had some success, and are continuously perfecting this assay for use with Desert bighorn sheep. 
 
Description Development of K-12 curriculum 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Discussions with schools regarding incorporation of disease ecology and bighorn sheep ecology into lesson plans.
Year(s) Of Engagement Activity 2021
 
Description Undergraduate research experience 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact The student (Ms Maisy Haley) presented a poster, entitled "The structure of bighorn sheep gut microbiome" at an undergraduate research symposium at the University of Warwick (online due to pandemic). The poster detailed the research undertaken during a competitively awarded summer project of the same name.
Year(s) Of Engagement Activity 2020