A Methodology for the Assessment and Prioritization of Genetic Biocontainment Technologies for Engineered Microbes.

Introduction: Organisms engineered with synthetic genes and genomes have the potential to play critical roles to address important issues in the environment, human health, and manufacturing. Engineered genetic biocontainment technologies are needed to manage the risks of unintended consequences when deploying these biological systems in consultation with the biosafety and biosecurity communities. Metrics measuring genetic biocontainment and a methodology to apply them are required to determine which genetic biocontainment technologies warrant further development for real-world applications.

A Machine Learning Method for Genome Engineering Design Tool Attribution.

As the ability to engineer biological systems improves with increasingly advanced technology, the risk of accidental or intentional release of a dangerous genetically modified organism becomes greater. It is important that authorities can carry out attribution for the source of a genetically modified biological agent release. In the absence of evidence that ties a release directly to the individuals responsible, attribution can be carried out in part by discovering the tools used to design the engineered genetic components, which can leave a signature in the DNA of the organism.

An in vitro platform for study of the human gut microbiome under an oxygen gradient.

The complex, dynamic environment of the human lower gastrointestinal tract is colonized by hundreds of bacterial species that impact health and performance. Ex vivo study of the functional interactions between microbial community members in conditions representative of those in the gut is an ongoing challenge. We have developed an in vitro 40-plex platform that provides an oxygen gradient to support simultaneous maintenance of microaerobic and anaerobic microbes from the gut microbiome that can aid in rapid characterization of microbial interactions and direct comparison of individual microbiome samples.

Demographic Patterns and Increasing Incidence of Cutaneous T-Cell Lymphoma in Louisiana.

This cohort study examines the demographic characteristics associated with the incidence of cutaneous T-cell lymphoma from 2000 to 2018 in Louisiana.

Standardizing Automated DNA Assembly: Best Practices, Metrics, and Protocols Using Robots.

The advancement of synthetic biology requires the ability to create new DNA sequences to produce unique behaviors in biological systems. Automation is increasingly employed to carry out well-established assembly methods of DNA fragments in a multiplexed, high-throughput fashion, allowing many different configurations to be tested simultaneously. However, metrics are required to determine when automation is warranted based on factors such as assembly methodology, protocol details, and number of samples.

Rate of serious infection in patients who are prescribed systemic biologic or nonbiologic agents for psoriasis: A large, single center, retrospective, observational cohort study.

Background: Systemic biologic and nonbiologic agents used to treat psoriasis may or may not contribute to serious infection (SI) risk. Safety data, particularly for biologic agents, and associated risk for SI, are scarce. The study's aim was to explore the risk for SI in psoriasis patients exposed to systemic biologic or nonbiologic agents.

Evidence for the association of Hashimoto's thyroiditis with psoriasis: a cross-sectional retrospective study.

Background: Current information indicates that psoriasis is a metabolic disorder with systemic manifestations. Reports have revealed an association between psoriasis and several chronic autoimmune disorders. For one of these disorders, Hashimoto's thyroiditis (HT), there are scarce, and relatively unconfirmed, reports of an association with psoriasis.

Determination of a Screening Metric for High Diversity DNA Libraries.

The fields of antibody engineering, enzyme optimization and pathway construction rely increasingly on screening complex variant DNA libraries. These highly diverse libraries allow researchers to sample a maximized sequence space; and therefore, more rapidly identify proteins with significantly improved activity. The current state of the art in synthetic biology allows for libraries with billions of variants, pushing the limits of researchers' ability to qualify libraries for screening by measuring the traditional quality metrics of fidelity and diversity of variants.

Improved PCR Amplification of Broad Spectrum GC DNA Templates.

Many applications in molecular biology can benefit from improved PCR amplification of DNA segments containing a wide range of GC content. Conventional PCR amplification of DNA sequences with regions of GC less than 30%, or higher than 70%, is complex due to secondary structures that block the DNA polymerase as well as mispriming and mis-annealing of the DNA. This complexity will often generate incomplete or nonspecific products that hamper downstream applications.

Redirector: designing cell factories by reconstructing the metabolic objective.

Advances in computational metabolic optimization are required to realize the full potential of new in vivo metabolic engineering technologies by bridging the gap between computational design and strain development. We present Redirector, a new Flux Balance Analysis-based framework for identifying engineering targets to optimize metabolite production in complex pathways. Previous optimization frameworks have modeled metabolic alterations as directly controlling fluxes by setting particular flux bounds.

Research, collaboration, and open science using web 2.0.

There is little doubt that the Internet has transformed the world in which we live. Information that was once archived in bricks and mortar libraries is now only a click away, and people across the globe have become connected in a manner inconceivable only 20 years ago. Although many scientists and educators have embraced the Internet as an invaluable tool for research, education and data sharing, some have been somewhat slower to take full advantage of emerging Web 2.

Large-scale identification of genetic design strategies using local search.

In the past decade, computational methods have been shown to be well suited to unraveling the complex web of metabolic reactions in biological systems. Methods based on flux-balance analysis (FBA) and bi-level optimization have been used to great effect in aiding metabolic engineering. These methods predict the result of genetic manipulations and allow for the best set of manipulations to be found computationally.

A pathway and genetic factors contributing to elevated gene expression noise in stationary phase.

Previous studies have identified factors associated with transcription and translation efficiency, such as promoter strength and mRNA sequences, that can affect stochasticity in gene expression. Here we present evidence for a pathway and associated genetic factors (namely, the ribosome modulation factor RMF and ppGpp) in Escherichia coli that contribute to heightened levels of gene expression noise during stationary phase. Endogenous cellular mechanisms that globally affect gene expression noise, such as those identified in this study, could provide phenotypic diversity under adverse conditions such as stationary phase.

A bottom-up approach to gene regulation.

The ability to construct synthetic gene networks enables experimental investigations of deliberately simplified systems that can be compared to qualitative and quantitative models. If simple, well-characterized modules can be coupled together into more complex networks with behaviour that can be predicted from that of the individual components, we may begin to build an understanding of cellular regulatory processes from the 'bottom up'. Here we have engineered a promoter to allow simultaneous repression and activation of gene expression in Escherichia coli.