ASU Scholarship Showcase

Background: Tissue-specific RNA plasticity broadly impacts the development, tissue identity and adaptability of all organisms, but changes in composition, expression levels and its impact on gene regulation in different somatic tissues are largely unknown. Here we developed a new method, polyA-tagging and sequencing (PAT-Seq) to isolate high-quality tissue-specific mRNA from Caenorhabditis elegans intestine, pharynx and body muscle tissues and study changes in their tissue-specific transcriptomes and 3’UTRomes.

Results: We have identified thousands of novel genes and isoforms differentially expressed between these three tissues. The intestine transcriptome is expansive, expressing over 30% of C. elegans mRNAs, while muscle transcriptomes are smaller but contain characteristic unique gene signatures. Active promoter regions in all three tissues reveal both known and novel enriched tissue-specific elements, along with putative transcription factors, suggesting novel tissue-specific modes of transcription initiation. We have precisely mapped approximately 20,000 tissue-specific polyadenylation sites and discovered that about 30% of transcripts in somatic cells use alternative polyadenylation in a tissue-specific manner, with their 3’UTR isoforms significantly enriched with microRNA targets.

Conclusions: For the first time, PAT-Seq allowed us to directly study tissue specific gene expression changes in an in vivo setting and compare these changes between three somatic tissues from the same organism at single-base resolution within the same experiment. We pinpoint precise tissue-specific transcriptome rearrangements and for the first time link tissue-specific alternative polyadenylation to miRNA regulation, suggesting novel and unexplored tissue-specific post-transcriptional regulatory networks in somatic cells.

Background: 3′untranslated regions (3′UTRs) are poorly understood portions of eukaryotic mRNAs essential for post-transcriptional gene regulation. Sequence elements in 3′UTRs can be target sites for regulatory molecules such as RNA binding proteins and microRNAs (miRNAs), and these interactions can exert significant control on gene networks. However, many such interactions remain uncharacterized due to a lack of high-throughput (HT) tools to study 3′UTR biology. HT cloning efforts such as the human ORFeome exemplify the potential benefits of genomic repositories for studying human disease, especially in relation to the discovery of biomarkers and targets for therapeutic agents. Currently there are no publicly available human 3′UTR libraries. To address this we have prepared the first version of the human 3′UTRome (h3′UTRome v1) library. The h3′UTRome is produced to a single high quality standard using the same recombinational cloning technology used for the human ORFeome, enabling universal operating methods and high throughput experimentation. The library is thoroughly sequenced and annotated with simple online access to information, and made publicly available through gene repositories at low cost to all scientists with minimal restriction.

Results: The first release of the h3′UTRome library comprises 1,461 human 3′UTRs cloned into Gateway® entry vectors, ready for downstream analyses. It contains 3′UTRs for 985 transcription factors, 156 kinases, 171 RNA binding proteins, and 186 other genes involved in gene regulation and in disease. We demonstrate the feasibility of the h3′UTRome library by screening a panel of 87 3′UTRs for targeting by two miRNAs: let-7c, which is implicated in tumorigenesis, and miR-221, which is implicated in atherosclerosis and heart disease. The panel is enriched with genes involved in the RAS signaling pathway, putative novel targets for the two miRNAs, as well as genes implicated in tumorigenesis and heart disease.

Conclusions: The h3′UTRome v1 library is a modular resource that can be utilized for high-throughput screens to identify regulatory interactions between trans-acting factors and 3′UTRs, Importantly, the library can be customized based on the specifications of the researcher, allowing the systematic study of human 3′UTR biology.

On-going efforts to understand the dynamics of coupled social-ecological (or more broadly, coupled infrastructure) systems and common pool resources have led to the generation of numerous datasets based on a large number of case studies. This data has facilitated the identification of important factors and fundamental principles which increase our understanding of such complex systems. However, the data at our disposal are often not easily comparable, have limited scope and scale, and are based on disparate underlying frameworks inhibiting synthesis, meta-analysis, and the validation of findings. Research efforts are further hampered when case inclusion criteria, variable definitions, coding schema, and inter-coder reliability testing are not made explicit in the presentation of research and shared among the research community. This paper first outlines challenges experienced by researchers engaged in a large-scale coding project; then highlights valuable lessons learned; and finally discusses opportunities for further research on comparative case study analysis focusing on social-ecological systems and common pool resources. Includes supplemental materials and appendices published in the International Journal of the Commons 2016 Special Issue. Volume 10 - Issue 2 - 2016.

Governing common pool resources (CPR) in the face of disturbances such as globalization and climate change is challenging. The outcome of any CPR governance regime is the influenced by local combinations of social, institutional, and biophysical factors, as well as cross-scale interdependencies. In this study, we take a step towards understanding multiple-causation of CPR outcomes by analyzing 1) the co-occurrence of Design Principles (DP) by activity (irrigation, fishery and forestry), and 2) the combination(s) of DPs leading to social and ecological success. We analyzed 69 cases pertaining to three different activities: irrigation, fishery, and forestry. We find that the importance of the design principles is dependent upon the natural and hard human made infrastructure (i.e. canals, equipment, vessels etc.). For example, clearly defined social boundaries are important when the natural infrastructure is highly mobile (i.e. tuna fish), while monitoring is more important when the natural infrastructure is more static (i.e. forests or water contained within an irrigation system). However, we also find that congruence between local conditions and rules and proportionality between investment and extraction are key for CPR success independent from the natural and human hard made infrastructure. We further provide new visualization techniques for co-occurrence patterns and add to qualitative comparative analysis by introducing a reliability metric to deal with a large meta-analysis dataset on secondary data where information is missing or uncertain.

Includes supplemental materials and appendices publications in International Journal of the Commons 2016 Special Issue. Volume 10 - Issue 2 - 2016

In 2013, the community of mathematical scientists and educators focused its collective attention on the mathematics of planet Earth. In the course of the year, a grassroots organization grew into an international partnership of more than 150 scientific societies, universities, research institutes, and organizations. The project, known as “Mathematics of Planet Earth 2013” (MPE2013), received the patronage of UNESCO and was a truly unique event. It brought the challenges facing our planet to the attention of the mathematics research community in numerous lectures, seminars, workshops, and special sessions at conferences of the professional societies; it sponsored the development of curriculum materials for all educational levels; it organized many outreach activities, including an international juried exhibit of virtual and physical displays for use in museums and schools; and it presented a series of public lectures by renowned scientists showing the public how mathematics contributes to our understanding of planet Earth, the nature of the challenges our planet is facing, and how mathematicians contribute to their solution. At the end of the year, MPE2013 morphed into “Mathematics of Planet Earth” (MPE).

Climate change and its interactions with complex socioeconomic dynamics dictate the need for decision makers to move from incremental adaptation toward transformation as societies try to cope with unprecedented and uncertain change. Developing pathways toward transformation is especially difficult in regions with multiple contested resource uses and rights, with diverse decision makers and rules, and where high uncertainty is generated by differences in stakeholders’ values, understanding of climate change, and ways of adapting. Such a region is the Murray-Darling Basin, Australia, from which we provide insights for developing a process to address these constraints. We present criteria for sequencing actions along adaptation pathways: feasibility of the action within the current decision context, its facilitation of other actions, its role in averting exceedance of a critical threshold, its robustness and resilience under diverse and unexpected shocks, its effect on future options, its lead time, and its effects on equity and social cohesion. These criteria could potentially enable development of multiple stakeholder-specific adaptation pathways through a regional collective action process. The actual implementation of these multiple adaptation pathways will be highly uncertain and politically difficult because of fixity of resource-use rights, unequal distribution of power, value conflicts, and the likely redistribution of benefits and costs. We propose that the approach we outline for building resilient pathways to transformation is a flexible and credible way of negotiating these challenges.

Globalization, the process by which local social-ecological systems (SESs) are becoming linked in a global network, presents policy scientists and practitioners with unique and difficult challenges. Although local SESs can be extremely complex, when they become more tightly linked in the global system, complexity increases very rapidly as multi-scale and multi-level processes become more important. Here, we argue that addressing these multi-scale and multi-level challenges requires a collection of theories and models. We suggest that the conceptual domains of sustainability, resilience, and robustness provide a sufficiently rich collection of theories and models, but overlapping definitions and confusion about how these conceptual domains articulate with one another reduces their utility. We attempt to eliminate this confusion and illustrate how sustainability, resilience, and robustness can be used in tandem to address the multi-scale and multi-level challenges associated with global change.

Social roles are thought to play an important role in determining the capacity for collective action in a community regarding the use of shared resources. Here we report on the results of a study using a behavioral experimental approach regarding the relationship between social roles and the performance of social-ecological systems. The computer-based irrigation experiment that was the basis of this study mimics the decisions faced by farmers in small-scale irrigation systems. In each of 20 rounds, which are analogous to growing seasons, participants face a two-stage commons dilemma. First they must decide how much to invest in the public infrastructure, e.g., canals and water diversion structures. Second, they must decide how much to extract from the water made available by that public infrastructure. Each round begins with a 60-second communication period before the players make their investment and extraction decisions. By analyzing the chat messages exchanged among participants during the communication stage of the experiment, we coded up to three roles per participant using the scheme of seven roles known to be important in the literature: leader, knowledge generator, connector, follower, moralist, enforcer, and observer. Our study supports the importance of certain social roles (e.g., connector) previously highlighted by several case study analyses. However, using qualitative comparative analysis we found that none of the individual roles was sufficient for groups to succeed, i.e., to reach a certain level of group production. Instead, we found that a combination of at least five roles was necessary for success. In addition, in the context of upstream-downstream asymmetry, we observed a pattern in which social roles assumed by participants tended to differ by their positions. Although our work generated some interesting insights, further research is needed to determine how robust our findings are to different action situations, such as biophysical context, social network, and resource uncertainty.

Large-N comparative studies have helped common pool resource scholars gain general insights into the factors that influence collective action and governance outcomes. However, these studies are often limited by missing data, and suffer from the methodological limitation that important information is lost when we reduce textual information to quantitative data. This study was motivated by nine case studies that appeared to be inconsistent with the expectation that the presence of Ostrom’s Design Principles increases the likelihood of successful common pool resource governance. These cases highlight the limitations of coding and analyzing Large-N case studies.

We examine two issues: 1) the challenge of missing data and 2) potential approaches that rely on context (which is often lost in the coding process) to address inconsistencies between empirical observations theoretical predictions. For the latter, we conduct a post-hoc qualitative analysis of a large-N comparative study to explore 2 types of inconsistencies: 1) cases where evidence for nearly all design principles was found, but available evidence led to the assessment that the CPR system was unsuccessful and 2) cases where the CPR system was deemed successful despite finding limited or no evidence for design principles. We describe inherent challenges to large-N comparative analysis to coding complex and dynamically changing common pool resource systems for the presence or absence of design principles and the determination of “success”. Finally, we illustrate how, in some cases, our qualitative analysis revealed that the identity of absent design principles explained inconsistencies hence de-facto reconciling such apparent inconsistencies with theoretical predictions. This analysis demonstrates the value of combining quantitative and qualitative analysis, and using mixed-methods approaches iteratively to build comprehensive methodological and theoretical approaches to understanding common pool resource governance in a dynamically changing context.

Institutions, the rules of the game that shape repeated human interactions, clearly play a critical role in helping groups avoid the inefficient use of shared resources such as fisheries, freshwater, and the assimilative capacity of the environment. Institutions, however, are intimately intertwined with the human, social, and biophysical context within which they operate. Scholars typically are careful to take this context into account when studying institutions and Ostrom’s Institutional Design Principles are a case in point. Scholars have tested whether Ostrom’s Design Principles, which specify broad relationships between institutional arrangements and context, actually support successful governance of shared resources. This article further contributes to this line of research by leveraging the notion of institutional design to outline a research trajectory focused on coupled infrastructure systems in which institutions are seen as one class of infrastructure among many that dynamically interact to produce outcomes over time.