| 1. |
- Hillier, Charles, et al.
(författare)
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Landscape of the Plasmodium Interactome Reveals Both Conserved and Species-Specific Functionality
- 2019
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Ingår i: Cell Reports. - : Elsevier. - 2211-1247. ; 28:6, s. 1635-1647
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Tidskriftsartikel (refereegranskat)abstract
- Malaria represents a major global health issue, and the identification of new intervention targets remains an urgent priority. This search is hampered by more than one-third of the genes of malaria-causing Plasmodium parasites being uncharacterized. We report a large-scale protein interaction network in Plasmodium schizonts, generated by combining blue native-polyacrylamide electrophoresis with quantitative mass spectrometry and machine learning. This integrative approach, spanning 3 species, identifies > 20,000 putative protein interactions, organized into 600 protein clusters. We validate selected interactions, assigning functions in chromatin regulation to previously unannotated proteins and suggesting a role for an EELM2 domain-containing protein and a putative microrchidia protein as mechanistic links between AP2-domain transcription factors and epigenetic regulation. Our interactome represents a high-confidence map of the native organization of core cellular processes in Plasmodium parasites. The network reveals putative functions for uncharacterized proteins, provides mechanistic and structural insight, and uncovers potential alternative therapeutic targets.
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| 2. |
- Holm, Poul, et al.
(författare)
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Collaboration between the natural, social and human sciences in Global Change Research
- 2013
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Ingår i: Environmental Science and Policy. - : Elsevier BV. - 1462-9011. ; 28, s. 25-35
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Tidskriftsartikel (refereegranskat)abstract
- In nearly all domains of Global Change Research (GCR), the role of humans is a key factor as a driving force, a subject of impacts, or an agent in mitigating impacts and adapting to change. While advances have been made in the conceptualisation and practice of interdisciplinary Global Change Research in fields such as climate change and sustainability, approaches have tended to frame interdisciplinarity as actor-led, rather than understanding that complex problems which cut across disciplines may require new epistemological frameworks and methodological practices that exceed any one discipline. GCR studies must involve from their outset the social, human, natural and technical sciences in creating the spaces of interdisciplinarity, its terms of reference and forms of articulation. We propose a framework for funding excellence in interdisciplinary studies, named the Radically Inter- and Trans-disciplinary Environments (RITE) framework. RITE includes the need for a realignment of funding strategies to ensure that national and international research bodies and programmes road-map their respective strengths and identified areas for radical interdisciplinary research; then ensure that these areas can and are appropriately funded and staffed by talented individuals who want to apply their creative scientific talents to broader issues than their own field in the long term, rather than on limited scope (5 year and less) research projects. While our references are mostly to Europe, recommendations may be applicable elsewhere. (C) 2012 Elsevier Ltd. All rights reserved.
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| 3. |
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| 4. |
- Palsson, Gisli, et al.
(författare)
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Reconceptualizing the 'Anthropos' in the Anthropocene : Integrating the social sciences and humanities in global environmental change research
- 2013
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Ingår i: Environmental Science and Policy. - : Elsevier BV. - 1462-9011 .- 1873-6416. ; 28, s. 3-13
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Tidskriftsartikel (refereegranskat)abstract
- There is growing recognition that humans are faced with a critical and narrowing window of opportunity to halt or reverse some of the key indicators involved in the environmental crisis. Given human activities' scale and impact, as well as the overly narrow perspectives of environmental research's dominant natural sciences, a major effort is necessary to place the perspectives and insights of the humanities' and social sciences' perspectives and insights at the forefront. Such effort will require developing integrated approaches, projects, and institutions that truly do so. This article's goal is to help mobilize the social sciences and the humanities on the topic of sustainability transitions, but also call for a meaningful research agenda to acknowledge the profound implications of the advent of the Anthropocene epoch. We formulate the need for an innovative research agenda based on a careful consideration of the changing human condition as linked to global environmental change. The humanities and social sciences will need to change and adapt to this pressing, historic task.
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| 5. |
- Russell, Andrew J.C., et al.
(författare)
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Regulators of male and female sexual development are critical for the transmission of a malaria parasite
- 2023
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Ingår i: Cell Host and Microbe. - : Cell Press. - 1931-3128 .- 1934-6069. ; 31:2, s. 305-319.e10
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Tidskriftsartikel (refereegranskat)abstract
- Malaria transmission to mosquitoes requires a developmental switch in asexually dividing blood-stage parasites to sexual reproduction. In Plasmodium berghei, the transcription factor AP2-G is required and sufficient for this switch, but how a particular sex is determined in a haploid parasite remains unknown. Using a global screen of barcoded mutants, we here identify genes essential for the formation of either male or female sexual forms and validate their importance for transmission. High-resolution single-cell transcriptomics of ten mutant parasites portrays the developmental bifurcation and reveals a regulatory cascade of putative gene functions in the determination and subsequent differentiation of each sex. A male-determining gene with a LOTUS/OST-HTH domain as well as the protein interactors of a female-determining zinc-finger protein indicate that germ-granule-like ribonucleoprotein complexes complement transcriptional processes in the regulation of both male and female development of a malaria parasite.
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| 6. |
- Zhang, Wensheng, et al.
(författare)
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The BAF and PRC2 Complex Subunits Dpf2 and Eed Antagonistically Converge on Tbx3 to Control ESC Differentiation
- 2019
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Ingår i: Cell Stem Cell. - : CELL PRESS. - 1934-5909 .- 1875-9777. ; 24:1, s. 138-
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Tidskriftsartikel (refereegranskat)abstract
- BAF complexes are composed of different subunits with varying functional and developmental roles, although many subunits have not been examined in depth. Here we show that the Baf45 subunit Dpf2 maintains pluripotency and ESC differentiation potential. Dpf2 co-occupies enhancers with Oct4, Sox2, p300, and the BAF subunit Brg1, and deleting Dpf2 perturbs ESC self-renewal, induces repression of Tbx3, and impairs mesendodermal differentiation without dramatically altering Brg1 localization. Mesendodermal differentiation can be rescued by restoring Tbx3 expression, whose distal enhancer is positively regulated by Dpf2-dependent H3K27ac maintenance and recruitment of pluripotency TFs and Brg1. In contrast, the PRC2 subunit Eed binds an intragenic Tbx3 enhancer to oppose Dpf2-dependent Tbx3 expression and mesendodermal differentiation. The PRC2 subunit Ezh2 likewise opposes Dpf2-dependent differentiation through a distinct mechanism involving Nanog repression. Together, these findings delineate distinct mechanistic roles for specific BAF and PRC2 subunits during ESC differentiation.
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