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Development of an Agent-Based Model for Understanding Mechanisms of Pneumonia Transmission in Bighorn Sheep

We have a new MAG!

Project Team: Ryan Long (PI), Nicole Bilodeau, Aniruddha Belsare

Start Date: October 1, 2018

The models developed during this MAG project will be used to develop a better understanding of pneumonia dynamics in bighorn sheep populations and guide further research questions. The long-term goal of our work is to support the Idaho Department of Fish and Game in developing locale-specific disease management strategies for bighorn sheep populations. We will use the results of our model to develop and support a new NSF-EEID proposal to be submitted in November 2019.

Pneumonia in bighorn sheep (Ovis canadensis) is a multifactorial, microbiologically complex disease that poses a significant threat to populations of bighorn sheep throughout their range. Recurrent spillover events and prolonged persistence of pathogens in bighorn sheep populations have contributed to numerous die-offs in the lower 48 states. The bacterium, Mycoplasma ovipneumoniae, has been shown to be a primary agent necessary for initiating epizootics. Though M. ovipneumoniae does not act alone, it is the first species to invade the lungs and predispose sheep to polymicrobial pneumonia.

M. ovipneumoniae is commonly carried by domestic sheep and goats, and strain typing data support the occurrence of recurrent spillover of M. ovipneumoniae from domestic small ruminants into bighorn sheep populations. Typically, affected bighorn sheep herds have an all-age die-off with 15-100% mortality. Following such all-age die-offs, some of the infected adults remain a persistent source of M. ovipneumoniae (asymptomatic carriage; Besser et al. 2013). These ‘carriers’ underpin the persistence of the disease in bighorn sheep populations and its population-limiting effect. Carriers primarily transmit the pathogen to naïve lambs and are responsible for low lamb survival to weaning for several years following die-offs (Cassirer et al.2013; Manlove et al. 2016). However, pathogen transmission risk is not constant across all infected hosts – Manlove et al. (2017) show that the transmission risk is much higher from infected dams than from dry ewes and yearlings.

Bighorn pneumonia represents a highly complex and heterogenous disease system. Furthermore, the uncertainties associated with our understanding of this system contribute to conflict among wildlife and livestock stakeholders over land use and management practices. This is particularly relevant because current disease management strategies mainly focus on reducing spillover from domestic sheep and goats.

One of the main purposes of this modeling work is to provide a decision-making context for effective management of pneumonia in wild populations of bighorn sheep. For example, we hope to answer questions such as: i) How would varying group dynamics and levels of connectivity among populations influence disease transmission?; ii) How can the landscape be modified to reduce the risk of disease transmission?; iii) How do varying levels of home-range fidelity change population dynamics?; iv) How do various levels of behavioral plasticity influence the ability of bighorn to utilize the nutritional landscape optimally?; v) Can ‘superspreaders’ explain the observed patterns of disease in bighorn sheep populations?; vi) How will climate change affect use of the landscape by bighorn?

Modeling Access Grants

Project 4: Bridging Mathematical and Statistical Models of Microbial Populations

Project Director: Chris Remien

Project Team: Benjamin Ridenhour, Janet Williams, Mark McGuire

The human body is host to a myriad of microbial communities, many of which are thought to perform tasks critical to maintaining health and avoiding disease. Understanding how microbes interact with each other and their environment is critical to the longer-term goals of manipulating microbiomes to promote health, designing synthetic microbial communities to perform tasks, and inferring stability to assess risk. This research will provide a critical step in enhancing our ability to infer interactions governing the population dynamics of constituent members of microbiomes over time.

Research Projects

Undergraduate Research at the U of I

CMCI is pleased to contribute to the research efforts at the University of Idaho and provide opportunities for students to gain hands-on field experience. Why is it important? President Chuck Staben recently asked David Pfeiffer, Director of the Office of Undergraduate Research, the same question and shared his answer in the Friday Letter –

President Chuck Staben: Why is undergraduate research, scholarship and creative activity so important? What do such opportunities mean for students?

David Pfeiffer: Research projects, scholarly activities and creative activities are fundamentally different from class work and the experience of doing them can engage students in wholly different ways. They demand a kind of tenacity and creativity that often isn’t fully realized in traditional classes and labs. Collectively, they are recognized as among a handful of high-impact educational practices that help foster critical thinking skills, innovation and independence in students. As such, these experiences help better prepare students for success during their degrees and beyond, regardless of their career path. Employers are not in the dark on this, and they are increasingly looking for evidence of these types of experiences on students’ resumés.

To read some of the current stories on campus about on-going research projects, check out Vandals in Focus 2018, which features some of the fascinating experiences available to students.

Research Projects

Determining the Role of Albumin Conformation in Enhanced Bone Repair and Regeneration

Project Team: Matthew Bernards, Nathan Schiele, Dharmeshkumar Patel, Stephanie Haag

In the US, over 130,000 surgical procedures each year require a bone graft material, but almost 30% of grafts fail. Recent studies have implicated albumin as important during bone repair and it has been adapted for improving scaffold integration with bone tissue. This is important because albumin is abundant and cost-effective. In contrast, however, are studies that demonstrate albumin blocking cell adhesion to biomaterials. These contradictions indicate that albumin is bioactive only when in specific conformations. The over-arching goal of this research effort is to deliver bioactive albumin via a tissue engineering platform for enhanced bone repair and regeneration. The development of this platform will address the clinical need for a bone graft with reduced failure rates. To achieve this goal, the bioactive conformation of albumin responsible for bone repair must be identified before it can be incorporated into a scaffold, and this is the objective of the proposed investigation. Our central hypothesis is that albumin has a bioactive conformation that promotes bone repair, that is imparted to albumin upon calcium binding.

First, we will use molecular modeling to determine the conformational landscape of calcium-free and calcium-bound albumin. The conformational preferences of albumin for various calcium-bound conditions will be determined using molecular modeling. Determining conformational preferences of a protein is a challenging problem in molecular modeling so we will tackle it using molecular dynamics or Monte Carlo simulations of coarse-grained protein models. These approaches allow for large-scale conformational changes within the timescale of the simulations. If our hypothesis is correct then changing the binding pattern for calcium will make specific conformation(s) more stable – and these conformations will promote cell adhesion. In parallel, we will identify conformation changes in albumin induced by calcium with Fourier transform infrared spectroscopy (FTIR). The conformational states of albumin adsorbed to tissue culture polystyrene in both a cell adhesive and nonadhesive conformation will be probed using FTIR. After identifying the critical calcium concentration that induces a cell adhesive conformation to albumin, we will use FTIR to quantify differences in the secondary structure of the adsorbed species. These will be directly compared to molecular modeling results obtained in Aim 1, to better delineate conformational changes that facilitate cell adhesion. If our hypothesis is correct then there should be significant changes in the secondary structure upon exposure to calcium.

By pairing molecular modeling with empirical evidence of the secondary structure of albumin it will be possible to delineate the bioactive region of albumin more clearly. This represents a significant step towards the therapeutic application of albumin or subdomains of albumin for bone tissue repair from an implanted scaffold.

Pilot Programs