Summary
Phagocytosis is required for a broad range of physiological functions, from pathogen defense to tissue homeostasis, but mechanisms required for phagocytosis of diverse substrates remain incompletely understood. Here, we develop a rapid magnet-based phenotypic screening strategy, and perform eight genome-wide CRISPR screens in human cells to identify genes regulating phagocytosis of distinct substrates. After validating select hits in focused mini-screens, orthogonal assays and primary human macrophages, we demonstrate that 1) the previously-uncharacterized gene NHLRC2 is a central player in phagocytosis, regulating RhoA-Rac1 signaling cascades that control actin polymerization and filopodia formation, 2) very long chain fatty acids are essential for efficient phagocytosis of certain substrates, and 3) the previously-uncharacterized Alzheimer’s disease-associated gene TM2D3 can preferentially influence uptake of amyloid-β aggregates. These findings illuminate new regulators and core principles of phagocytosis, and more generally establish an efficient method for unbiased identification of cellular uptake mechanisms across diverse physiological and pathological contexts.
smMIP-based genetic testing enables automated and reliable analysis of the coding sequences of BRCA1 and BRCA2. The use of single-molecule tags, double-tiled targeted enrichment, and capturing and sequencing in duplo, in combination with automated library preparation and data analysis, results in a robust process and reduces routine turnaround times. Furthermore, smMIP-based copy number variation analysis could make independent copy number variation tools like multiplex ligation-dependent probes amplification dispensable.
This paper uses a reflective method to gather findings with relation to a collaborative governance approach for the sociotechnical transition to a low carbon society in a regional context. As top-down and bottom-up approaches to sustainable transitions have proven insufficient in bringing about the necessary changes required to meet the demands of climate action, more collaborative approaches between local communities, national public bodies and research organisations are warranted. Within this, there is a need to understand the dynamics of collaborative governance for participants in the process. Through a process of reflective practice, this paper outlines the networks, personal capacities, organisational capacities, benefits and challenges of collaborative governance partnerships for sustainable transitions from the perspective of individuals within a collaborative committee working on a regional transition project on the Dingle Peninsula, Co Kerry, Ireland. Alongside this, some solutions to challenges outlined through reflection are highlighted. This research paper highlights the need for the incorporation of reflective practice within collaborative governance for the socio-technical transition to a low-carbon society.
The paper develops a methodological approach that acts as a tool for active change agents working in community and just transition contexts to increase their capacity to engage a wider public in planning. An innovative contribution is made to the literature through the development of a participatory action research (PAR) based approach to social network analysis using a participatory mapping method with relation to sustainable transitions. The method comprises a participatory network mapping approach, adapted from the Net-Map toolkit, which is applied to a multi-stakeholder approach to realising a regional sustainability transition in the Republic of Ireland. Dingle Peninsula 2030 is an initiative aiming to transition a geographic region in the South West of Ireland to a low-carbon society by 2030 across the sectors of energy, agriculture, transport, education, employment, marine and tourism. Due to the scope of the overall project, a diverse range of stakeholders are involved. The method developed is used to undertake a qualitative collaborative social network analysis. The paper focuses on method, by analysing and reflecting upon the use of this participatory approach, in the initial stages of the overall project, in addressing complex sustainability and just transition challenges as they are revealed through a multi-stakeholder approach. Within this, the themes of participatory justice, social learning and visualising complexity are explored; and benefits and future improvements are outlined through reflections from both the researcher and the participant community.
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