Genetic Engineering and Society Center

Research Thrust 1 (RT1) combines multi-omic investigations to determine the mechanisms of microbial colonization and aims to develop sensor and tracking technologies for diagnosing built environment health at varying resolutions (i.e., personal, room, and building level).

RT1 researchers will develop tracking tools that combine phylogenetic and functional aspects through the integration of personal and environmental microbiome data with microbial dark matter characteristics. These tools will include genome-enabled approaches that can target uncultivated microbial taxa and increase our understanding of microbial diversity, phylogenetic relationships, metabolic capabilities, and interactions in the built environment as well as functional approaches via meta-omics. In combination, these approaches will deepen our databases enabling the identification of key molecules and the development of sensors for health assessment of the built environment.

Projects in RT1 will apply and expand fundamental knowledge in microbiome monitoring. We will begin by developing approaches for monitoring and connecting the personal and the environmental microbiome as well as determine functional signatures that can diagnose built environment health. RT1 data will provide the early building blocks for monitoring the built environment microbiome as well that of its occupants, identifying the biomarkers that signal a healthy built environment, and inform PreMiEr’s future sensor development work.

Projects in Research Thrust 2 (RT2) will build the toolbox needed for targeting the delivery/removal of desired genetic features or vectors in the built environment as well as enabling functional modulation in an established microbial community.

RT2 researchers will use their knowledge of delivery systems and nanoparticle transport in complex environments to develop the requisite toolbox for microbiome engineering in the built environment. Initial projects will focus on limiting the spread of animicrobial resistance (AMR) in built microbiomes as well as targeting the built environment water microbiome as there is a critical body of work linking the microbiome of premise plumbing to adverse effects in the built environment. Later efforts will transition to engineering solutions to limiting pathogens and bioaerosols as PreMiEr’s research matures.

Projects in Research Thrust 3 (RT3) will develop predictive models that incorporate spatiotemporal methods, generative modeling concepts, and machine learning approaches to analyze built environment microbiomes.

RT3 projects will focus on the development of predictive models that identify factors that contribute to microbiome compositional variations, and microbiome signatures that associate with specific health outcomes, which in turn will inform built environment health signature identification.

Initial projects will focus on various facets of the predictive models using existing large datasets and then incorporate PreMiEr datasets from Research Thrust 1 as those are generated. Spatial-temporal statistical models for microbiome compositions will be constructed that can characterize the personalized equilibrium of an individual’s microbiome compositions and detect anomalies, or deviation from the normal equilibrium. This information will be crucial in linking to the environmental microbiome. Another project will integrate functional information to decipher the functional meanings of the signals identified in the predictive models. Finally, improvements in the bioinformatic preprocessing pipelines using machine learning approaches will enhance the sensitivity and specificity of the predictive models.

In Research Core A, PreMiEr’s microbiome tracking devices (personal and environmental sensors), targeted delivery tools and predictive microbiome modeling framework will be integrated to measure, predict and improve the health of the built environment microbiome in six model testbed environments:

1. Environmental Chambers
2. Artificial Gut
3. Tiny House
4. Duke University Smart Home
5. Hospitals, and
6. Bolivian Homes

The PreMiEr Data Analytics Core is an integral part of the success of the ERC by supporting the hardware and software needs of all other research thrusts. Its goals can be broken down into three main areas.

1. A seamless, central repository with core services providing

• Scientific data processing and analysis support
• Report and figure creation services
• Seamless and automated ability to start and modify processes and analyses

2. Ensuring transparency and reproducibility

• Eliminate “silos” of data
• Allow teams to easily work together
• Publish results that fully expose the processing pipeline and publish virtualized containers
• Support version control

3. Being “hardware agnostic”

• Allow any PreMiEr researcher (or other interested scientist) to faithfully reproduce analyses regardless of hardware
• Provide virtualized containers for on-campus and other systems, including a primary system at UNC-Charlotte, the ViCAR system at North Carolina A&T, and the cloud

All research and activities within PreMiEr are guided and done in collaboration with the Societal and Ethical Implications (SEI) Core.

PreMiEr’s work evokes a diverse range of SEI issues at the intersection of health and environmental risk, medical ethics, research ethics, environmental release of GMOs, public trust and perceptions, social equity, gender and racial inequities, privacy and regulation, and responsible governance.

PreMiEr provides a unique opportunity to engage researchers, engineers, stakeholders, and publics in emerging conversations about engineered microbiomes in built environments

The ERC also enables novel and ground-breaking scholarly examination of SEI aspects of microbiome engineering for built environments

Diversity and Culture of Inclusion Overview
PreMiEr prioritizes diversity and culture of inclusion (DCI) recognizing that our ERC cannot maximize impacts without intentional efforts to foster both and promote an equitable environment where all can thrive. PreMiEr grew out of an existing 5-year partnership between Duke (HWI) and North Carolina A&T (HBCU). This partnership taught both universities lessons on the practical implementation of diversity and culture of inclusion. The addition of North Carolina State (NC State), UNC Chapel Hill (UNC-CH), and UNC Charlotte (UNC-C) to this team has provided us with an even greater opportunity to institutionalize DCI in every aspect of PreMiEr’s function.

PreMiEr is dedicated to building a diverse faculty and trainee population as a means to broaden participation in STEM. This will be achieved by leveraging recruitment of underserved populations across all campuses and working to develop research pipelines between Duke, UNC-CH, UNC-C, NCSU and NCAT. We see the key to this effort stemming from PreMiEr advancing a bold and reimagined research agenda that not only benefits the historically privileged but also addresses the needs of historically marginalized communities. We recognize that while diversity is known to impact creativity by fueling innovation, diversity without an inclusive culture and equitable framework can significantly limit creativity and decrease participants’ commitment levels. Thus, our primary goal is to develop an inclusive and equitable culture where voices from diverse stakeholders are acknowledged and all participants are treated with respect and their ideas evaluated with the highest standards of scientific integrity.

PreMiEr’s commitment to DCI is evidenced by the composition of our ERC. Our leadership team is composed of 60% females and 20% URM faculty, while our senior personnel is composed of 43.6% females and 12.8% faculty from racially marginalized communities. We are committed to promoting an equitable academic and social environment where minority scholars can flourish. This will be achieved through leadership development for ERC leaders/mentors including effective communication strategies, fostering a thriving & engaging environment, and promoting an inclusive environment; and 3) feedback from PreMiEr’s advisory boards to our Executive and Steering Committees.

The four Diversity and Culture of Inclusion goals are to:

1. Continue to prioritize and increase diversity, equity and inclusion across PreMiEr’s institutional ecosystem
2. Promote an equitable academic and social environment where minority scholars can flourish
3. Prioritize the recruitment and retention of diverse trainees
4. Broaden participation in microbiome sciences

Award Abstract # 2133504: NSF Engineering Research Center for Precision Microbiome Engineering (PreMiEr)

Microbes have colonized and adapted to most every environment on Earth, including the built environments that humans have created, such as the homes where we live and the pipes that bring us drinking water. It has been well established that microbial communities, or microbiomes, that colonize people have a direct influence on human health. The microbiome of the built environment, in particular, has gained increasing recognition for its key role in human health through its interaction with the human microbiome. However, despite this knowledge, no systematic infrastructure exists to decipher how microbial systems adapt to and grow within built environments, impeding our ability to diagnose built environment health and harness the power inherent to those microbiomes.

The Engineering Research Center for Precision Microbiome Engineering (PreMiEr) will create microbiome-based diagnostic tools and develop microbiome engineering approaches to monitor and operate built environments that maximize human health protection. Informed by societal needs and research-stakeholder teams, PreMiEr’s research design will work to prevent the spread of infectious agents, promote the colonization of beneficial microorganisms, and lead to strategies for controlling pandemics and antibiotic resistance—phenomena that have led to over six million deaths worldwide (as of June 2022) and cost the global economy an estimated $8 trillion in the last year alone. Integral to its research vision, PreMiEr will create diverse and inclusive interdisciplinary research and training hubs where engineers, microbiologists, social scientists, and ethicists work alongside theorists, model builders, and computational scientists to develop technologies that enable transformative engineering discoveries in safe, sustainable and responsible ways.

Our capacity to engineer microbiomes requires a fundamental understanding of concepts of community ecology and an ability to track, control, and model those interactions. To apply microbiome engineering to real-world systems, community level interactions must be integrated into a comprehensive, scalable modeling framework that requires iterative evaluation and validation in model testbeds. PreMiEr’s research organization is designed to generate fundamental understanding across these levels and functionalities, culminating in the development of a framework that enables the biodesign of smart and healthy built environments. PreMiEr will leverage advances in high-throughput genomic sequencing, high-resolution mass spectrometry, computational performance, and statistical modeling to unravel previously unknown mechanistic interactions. Enabling technologies will be developed to detect and define interactions in the built environment, including approaches that probe microbial dark matter for the development of built-environment health diagnostic tools; methods for targeted delivery of desired genetic features and microbial vectors; tools for fine in situ functional tuning; and predictive scalable statistical microbiome engineering models that consider high dimensionality, sparsity, and heterogeneity. These new technology elements will enable us to test hypotheses related to microbiome assembly and function.

Importantly, by incorporating social scientists and ethicists into PreMiEr’s research framework, non-social scientists’ work will be informed by consideration of the ethical, societal, and policy implications of their microbiome engineering discoveries. Through rigorous evaluation and iterative refinement of curricula, and institutional practices designed to support a culture of convergence and the dissemination of findings, PreMiEr will contribute to best practices in domestic training. The PreMiEr ERC will include targeted recruitment of trainees from underrepresented groups, building upon existing partnerships with our nation’s largest HBCU, and will provide immersion in research and training at the interface of multiple disciplines to address complex challenges. PreMiEr will train the next generation of diverse and highly motivated engineers and scientists in technical and professional skills to compete in the emerging arenas of microbial science and engineering. Ultimately, our work will advance collaborations and discovery focused on environmental microbiomes to engineer healthy built environments.