Integrating protein-protein interaction networks with phenotypes reveals signs of interactions

A major objective of systems biology is to organize molecular interactions as networks and to characterize information-flow within networks. We describe a computational framework to integrate protein-protein interaction (PPI) networks and genetic screens to predict the “signs” of interactions (i.e. activation/inhibition relationships). We constructed a Drosophila melanogaster signed PPI network, consisting of 6,125 signed PPIs connecting 3,352 proteins that can be used to identify positive and negative regulators of signaling pathways and protein complexes. We identified an unexpected role for the metabolic enzymes Enolase and Aldo-keto reductase as positive and negative regulators of proteolysis, respectively. Characterization of the activation/inhibition relationships between physically interacting proteins within signaling pathways will impact our understanding of many biological functions, including signal transduction and mechanisms of disease

The one health landscape in sub-Saharan African countries

OBJECTIVES : One Health is transiting from multidisciplinary to transdisciplinary concepts and its viewpoints should move from ‘proxy for zoonoses’, to include other topics (climate change, nutrition and food safety, policy and planning, welfare and well-being, antimicrobial resistance (AMR), vector-borne diseases, toxicosis and pesticides issues) and thematic fields (social sciences, geography and economics). This work was conducted to map the One Health landscape in Africa. METHODS : An assessment of existing One Health initiatives in Sub-Saharan African (SSA) countries was conducted among selected stakeholders using a multi-method approach. Strengths, weaknesses, opportunities and threats to One Health initiatives were identified, and their influence, interest and impacts were semi-quantitatively evaluated using literature reviews, questionnaire survey and statistical analysis. RESULTS : One Health Networks and identified initiatives were spatiotemporally spread across SSA and identified stakeholders were classified into four quadrants. It was observed that imbalance in stakeholders' representations led to hesitation in buying-in into One Health approach by stakeholders who are outside the main networks like stakeholders from the policy, budgeting, geography and sometimes, the environment sectors. CONCLUSION : Inclusion of theory of change, monitoring and evaluation frameworks, and tools for standardized evaluation of One Health policies are needed for a sustained future of One Health and future engagements should be outputs- and outcomes-driven and not activity-driven. National roadmaps for One Health implementation and institutionalization are necessary, and proofs of concepts in One Health should be validated and scaled-up.https://www.journals.elsevier.com/one-healtham2022Veterinary Tropical Disease

Optimized gene editing technology for Drosophila melanogaster using germ line-specific Cas9

The ability to engineer genomes in a specific, systematic, and cost-effective way is critical for functional genomic studies. Recent advances using the CRISPR-associated single-guide RNA system (Cas9/sgRNA) illustrate the potential of this simple system for genome engineering in a number of organisms. Here we report an effective and inexpensive method for genome DNA editing in Drosophila melanogaster whereby plasmid DNAs encoding short sgRNAs under the control of the U6b promoter are injected into transgenic flies in which Cas9 is specifically expressed in the germ line via the nanos promoter. We evaluate the off-targets associated with the method and establish a Web-based resource, along with a searchable, genome-wide database of predicted sgRNAs appropriate for genome engineering in flies. Finally, we discuss the advantages of our method in comparison with other recently published approaches.Multidisciplinary SciencesSCI(E)46ARTICLE4719012-1901711

FlyRNAi.org—the database of the Drosophila RNAi screening center and transgenic RNAi project: 2017 update

The FlyRNAi database of the Drosophila RNAi Screening Center (DRSC) and Transgenic RNAi Project (TRiP) at Harvard Medical School and associated DRSC/TRiP Functional Genomics Resources website (http://fgr.hms.harvard.edu) serve as a reagent production tracking system, screen data repository, and portal to the community. Through this portal, we make available protocols, online tools, and other resources useful to researchers at all stages of high-throughput functional genomics screening, from assay design and reagent identification to data analysis and interpretation. In this update, we describe recent changes and additions to our website, database and suite of online tools. Recent changes reflect a shift in our focus from a single technology (RNAi) and model species (Drosophila) to the application of additional technologies (e.g. CRISPR) and support of integrated, cross-species approaches to uncovering gene function using functional genomics and other approaches