This article was published by the Office of Research and Economic Development in the October 2019 Scholars and Researchers newsletter. IMCI supports Zebrafish research through modeling via the Evolution of Tandemly-Replicated Opsin Genes: Molecular Models That Predict Spectral Shifts (which led to an article featured on the cover of Science magazine) and Bioinformatic Analysis of Immune-Dell-Derived, Regeneration-Specific Transcripts in Zebrafish Modeling Access Grants (MAG). MAGs are the bridge between a great idea and an actual project. The joint purchase of these new zebrafish aquatic housing systems is just one example of our focus on interdisciplinary, collaborative research.
Humans and zebrafish
have more in common than one might think. They share 70 percent of the same DNA
coding; and zebrafish muscles, blood, immune system, kidneys and even eyes
share many human features. Consequently, zebrafish are an important animal model
for human biomedical research.
Recognizing this, Professor Deborah Stenkamp and Assistant Professor Diana Mitchell, both cellular and molecular biology experts in U of I’s College of Science, proposed to conduct retinal regeneration and developmental studies on zebrafish. Such research could help us understand the mechanisms behind the successful regeneration and regulation of genes governing color vision. These studies can also help pave the way for new approaches to help treat humans with vision loss — and possibly other disorders that can deteriorate the nervous system.
To conduct these studies, Stenkamp and Mitchell needed a clean, contained environment to keep these disease-susceptible animals safe and healthy. Several U of I entities stepped in to provide $73,000 in funding for the solution: three stand-alone ‘fish rack’ containment systems with advanced filtration features. The Office of Research and Economic Development, College of Science, Department of Biological Sciences, Idaho NIH IDeA Network of Biomedical Research Excellence (INBRE) program, Institute for Bioinformatics and Evolutionary Studies (IBEST), and Institute for Modeling Collaboration and Innovation (IMCI) all helped support the effort.
racks will allow Stenkamp and Mitchell to perform ‘clean’ experiments on
zebrafish tissue regeneration and development – without any pathogenic microbes
that could complicate their experimental outcomes. The system, located in U of
I’s Laboratory Animal Research Facility (LARF), will also help future U of I
researchers conduct similar biomedical studies on zebrafish.
The three racks
feature a variety of small and large tanks, all monitored and controlled by a
computerized system that ensures a healthy environment for the fish. These
computers bring precise amounts of sodium bicarbonate – better known as baking
soda – into the water to ensure pH balance; deliver exact measurements of brine
to simulate brackish waters, where some zebrafish naturally live; and perform
various other functions. Water storage tanks are also included in the system as
a safeguard in case of system leaks or other water loss events.
Title: DNA and protein modeling for P/asmodium falciparum dhfr and dhps sequences derived from an existing study in Kenya
Project Team: Shirley Luckhart, Dharmesh Patel, JT Van Leuven
Start Date: June, 2019
The UI, USUHS, and USAMRU-K teams have collected human blood samples from study-enrolled Kenyan adults for an NIH-funded project focused on defining the impacts of HIV-malaria co-infection and HIV treatment.
We have completed deep sequencing, cleaning and clustering of dhfr and dhps genotypes and have identified frequencies for the dhfr and dhps SNPs known to be associated with sulfadoxine-pyrimethamine drug resistance.
However, given the AT-rich codon bias and mutation frequency of P. falciparum per asexual parasite cycle, we have noted other nucleotide substitutions in our sequences that we would like to explore with modeling.
We seek to classify whether these nucleotide changes are:
(1) substitutions that affect codon frequency but are synonymous,
(2) non-synonymous substitutions that are conservative, and
(3) non-synonymous substitutions that are non-conservative,
all of which could be predicted to alter protein structure or function.
Project Team: Paul Rowley, Jagdish Patel, Dharmesh Patel
Start Date: May 2019
Molecular dynamics simulations will help Principal Investigators Rowley and Jagdish Patel analyze FoldX. The team expects this research to lead to a publication and serve as the foundation for future grants to investigate haptoglobin evolution in other mammalian species that serve as reservoirs of trypanosomes.
Project Team: Kristopher Waynant, Darren Thompson, Tyler Siegford, Jacob Kennedy, Dharmesh Patel
Start Date: February 1, 2019
In preparation for a grant proposal to the National Institute for Dental and Craniofacial Research, CMCI Postdoctoral Fellow Dharmesh Patel will be dedicating some of his time over the next few months to prepare models for Chemistry faculty Kristopher Waynant and Darren Thompson.
The project title is, “Exploring glycosylation dependence on the bacterial affinity of the Mucin7 repeat peptide sequence with modeled and synthesized carbon-linked amino acid conjugates.”
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?