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1.
Bioessays ; 41(9): e1900048, 2019 09.
Article in English | MEDLINE | ID: mdl-31264253

ABSTRACT

The organization of the genome into topologically associated domains (TADs) appears to be a fundamental process occurring across a wide range of eukaryote organisms, and it likely plays an important role in providing an architectural foundation for gene regulation. Initial studies emphasized the remarkable parallels between TAD organization in organisms as diverse as Drosophila and mammals. However, whereas CCCTC-binding factor (CTCF)/cohesin loop extrusion is emerging as a key mechanism for the formation of mammalian topological domains, the genome organization in Drosophila appears to depend primarily on the partitioning of chromatin state domains. Recent work suggesting a fundamental conserved role of chromatin state in building domain architecture is discussed and insights into genome organization from recent studies in Drosophila are considered.


Subject(s)
CCCTC-Binding Factor/chemistry , Cell Cycle Proteins/metabolism , Chromatin/metabolism , Chromosomal Proteins, Non-Histone/metabolism , Drosophila Proteins/chemistry , Drosophila/genetics , Amino Acid Sequence , Animals , CCCTC-Binding Factor/metabolism , Chromatin/chemistry , Chromatin/genetics , Conserved Sequence , Drosophila Proteins/metabolism , Genome, Insect/genetics , Mammals/genetics , Protein Domains , Transcription, Genetic , Cohesins
2.
Metab Eng ; 60: 168-182, 2020 07.
Article in English | MEDLINE | ID: mdl-32335188

ABSTRACT

Bio-based production of industrial chemicals using synthetic biology can provide alternative green routes from renewable resources, allowing for cleaner production processes. To efficiently produce chemicals on-demand through microbial strain engineering, biomanufacturing foundries have developed automated pipelines that are largely compound agnostic in their time to delivery. Here we benchmark the capabilities of a biomanufacturing pipeline to enable rapid prototyping of microbial cell factories for the production of chemically diverse industrially relevant material building blocks. Over 85 days the pipeline was able to produce 17 potential material monomers and key intermediates by combining 160 genetic parts into 115 unique biosynthetic pathways. To explore the scale-up potential of our prototype production strains, we optimized the enantioselective production of mandelic acid and hydroxymandelic acid, achieving gram-scale production in fed-batch fermenters. The high success rate in the rapid design and prototyping of microbially-produced material building blocks reveals the potential role of biofoundries in leading the transition to sustainable materials production.


Subject(s)
Bacteria/metabolism , Industrial Microbiology/methods , Metabolic Engineering/methods , Benchmarking , Biosynthetic Pathways , Chemical Industry , Computer Simulation , Fermentation , Mandelic Acids/metabolism , Stereoisomerism
3.
PLoS One ; 15(11): e0242516, 2020.
Article in English | MEDLINE | ID: mdl-33211749

ABSTRACT

Small (s)RNAs play crucial roles in the regulation of gene expression and genome stability across eukaryotes where they direct epigenetic modifications, post-transcriptional gene silencing, and defense against both endogenous and exogenous viruses. It is known that Chlamydomonas reinhardtii, a well-studied unicellular green algae species, possesses sRNA-based mechanisms that are distinct from those of land plants. However, definition of sRNA loci and further systematic classification is not yet available for this or any other algae. Here, using data-driven machine learning approaches including Multiple Correspondence Analysis (MCA) and clustering, we have generated a comprehensively annotated and classified sRNA locus map for C. reinhardtii. This map shows some common characteristics with higher plants and animals, but it also reveals distinct features. These results are consistent with the idea that there was diversification in sRNA mechanisms after the evolutionary divergence of algae from higher plant lineages.


Subject(s)
Chlamydomonas reinhardtii/genetics , Genetic Loci , RNA, Antisense/genetics , RNA, Plant/genetics , Base Composition , Cluster Analysis , DNA Methylation , Evolution, Molecular , Gene Expression Regulation, Plant , Gene Library , Machine Learning , Molecular Sequence Annotation
4.
Sustain Prod Consum ; 20: 58-73, 2019 Oct.
Article in English | MEDLINE | ID: mdl-32051840

ABSTRACT

Emerging technologies are increasingly promoted on the promise of tackling the grand challenge of sustainability. A range of assessment and governance approaches seek to evaluate these claims, but these tend to be applied disparately and lack widespread operationalisation. They also face specific challenges, such as high levels of uncertainty, when it comes to emerging technologies. Building and reflecting on both theory and practice, this article develops a framework for Constructive Sustainability Assessment (CSA) that enables the application of sustainability assessments to emerging technologies as part of a broader deliberative approach. In order to achieve this, we discuss and critique current approaches to analytical sustainability assessment and review deliberative social science governance frameworks. We then develop the conceptual basis of CSA - blending life-cycle thinking with principles of responsible research and innovation. This results in four design principles - transdisciplinarity, opening-up, exploring uncertainty and anticipation - that can be followed when applying sustainability assessments to emerging technologies. Finally, we discuss the practical implementation of the framework through a three-step process to (a) formulate the sustainability assessment in collaboration with stakeholders, (b) evaluate potential sustainability implications using methods such as anticipatory life-cycle assessment and (c) interpret and explore the results as part of a deliberative process. Through this, CSA facilitates a much-needed transdisciplinary response to enable the governance of emerging technologies towards sustainability. The framework will be of interest to scientists, engineers, and policy-makers working with emerging technologies that have sustainability as an explicit or implicit motivator.

5.
Sci Rep ; 9(1): 19033, 2019 12 13.
Article in English | MEDLINE | ID: mdl-31836745

ABSTRACT

Tackling the pressing sustainability needs of society will require the development and application of new technologies. Biotechnology, emboldened by recent advances in synthetic biology, offers to generate sustainable biologically-based routes to chemicals and materials as alternatives to fossil-derived incumbents. Yet, the sustainability potential of biotechnology is not without trade-offs. Here, we probe this capacity for sustainability for the case of bio-based nylon using both deliberative and analytical approaches within a framework of Constructive Sustainability Assessment. We highlight the potential for life cycle CO2 and N2O savings with bio-based processes, but report mixed results in other environmental and social impact categories. Importantly, we demonstrate how this knowledge can be generated collaboratively and constructively within companies at an early stage to anticipate consequences and to inform the modification of designs and applications. Application of the approach demonstrated here provides an avenue for technological actors to better understand and become responsive to the sustainability implications of their products, systems and actions.

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