Explore the words cloud of the PRION2020 project. It provides you a very rough idea of what is the project "PRION2020" about.
The following table provides information about the project.
|Coordinator Country||Switzerland [CH]|
|Total cost||2˙500˙000 €|
|EC max contribution||2˙500˙000 € (100%)|
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
|Duration (year-month-day)||from 2015-11-01 to 2020-10-31|
Take a look of project's partnership.
|1||UNIVERSITAT ZURICH||CH (Zürich)||coordinator||2˙500˙000.00|
Transmissible spongiform encephalopathies (TSE) are caused by the ordered aggregation of PrPC into prions consisting of PrPSc. Similar pathogenetic principles operate in Alzheimer’s and Parkin-son’s disease, and a growing list of further diseases whose prevalence is steadily rising. Familial TSE are invariably associated with PrPC mutations, and the dearth of genetic modifiers has hampered our understanding of prion diseases. Therefore, the first objective of my proposal utilizes a cell-based high-throughput quantitative prion replication assay (developed during my previous ERC instalment) for genome-wide unbiased screens employing new genetics tools (CRISPR, siRNA li-braries, next-gen sequencing) to identify modifiers of prion uptake, replication, and secretion. The second objective aims at clarifying the basis of prion neurotoxicity and will be developed along two alleys: (a) we will uncover the molecular basis of spongiosis (the neuronal vacuolation characteristic of prion diseases), which we suspect to be a main driver of pathology, and (b) we will perform CRISPR-based synthetic lethality screens to identify genes that become essential to prion-infected cell lines (which do not experience prion toxicity) and may not be expressed by neurons. The third objective is to understand the function of PrPC in cellular physiology, and focuses on our evidence that (a) PrPC interacts with an orphan G-protein coupled receptor to maintain peripheral myelin integrity and (b) that PrPC may trigger cell death in response to ER stressors. While certain pathways of degeneration will undoubtedly be specific to prion infections, I expect that some targets will prove common to a variety of protein aggregation diseases including Alzheimer’s and Parkinson’s disease, and may perhaps translate into novel diagnostics and therapeutics. Hence the proposed project may not only open new perspectives in prion biology but also yield insights applicable to much more common diseases.
|year||authors and title||journal||last update|
Marie-Angela Wulf, Assunta Senatore, Adriano Aguzzi
The biological function of the cellular prion protein: an update
published pages: , ISSN: 1741-7007, DOI: 10.1186/s12915-017-0375-5
|BMC Biology 15/1||2019-07-05|
Ballmer, Boris A.; Moos, Rita; Liberali, Prisca; Pelkmans, Lucas; Hornemann, Simone; Aguzzi, Adriano
Modifiers of prion protein biogenesis and recycling identified by a highly parallel endocytosis kinetics assay
published pages: 8356-8368., ISSN: 0021-9258, DOI: 10.5167/uzh-136555
|Journal of Biological Chemistry 292(20)||2019-07-05|
Mario Nuvolone, Mario Hermann, Silvia Sorce, Giancarlo Russo, Cinzia Tiberi, Petra Schwarz, Eric Minikel, Despina Sanoudou, Pawel Pelczar, Adriano Aguzzi
Strictly co-isogenic C57BL/6J- Prnp âˆ’/âˆ’ mice: A rigorous resource for prion science
published pages: 313-327, ISSN: 0022-1007, DOI: 10.1084/jem.20151610
|The Journal of Experimental Medicine 213/3||2019-07-05|
Karl Frontzek, Manuela Pfammatter, Silvia Sorce, Assunta Senatore, Petra Schwarz, Rita Moos, Katrin Frauenknecht, Simone Hornemann, Adriano Aguzzi
Neurotoxic Antibodies against the Prion Protein Do Not Trigger Prion Replication
published pages: e0163601, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0163601
|PLOS ONE 11/9||2019-07-05|
Adriano Aguzzi, Asvin K.K. Lakkaraju, Karl Frontzek
Toward Therapy of Human Prion Diseases
published pages: 331-351, ISSN: 0362-1642, DOI: 10.1146/annurev-pharmtox-010617-052745
|Annual Review of Pharmacology and Toxicology 58/1||2019-07-05|
Claudia Scheckel, Adriano Aguzzi
Prions, prionoids and protein misfolding disorders
published pages: 405-418, ISSN: 1471-0056, DOI: 10.1038/s41576-018-0011-4
|Nature Reviews Genetics 19/7||2019-07-05|
Caihong Zhu, Uli S. Herrmann, Jeppe Falsig, Irina Abakumova, Mario Nuvolone, Petra Schwarz, Katrin Frauenknecht, Elisabeth J. Rushing, Adriano Aguzzi
A neuroprotective role for microglia in prion diseases
published pages: 1047-1059, ISSN: 0022-1007, DOI: 10.1084/jem.20151000
|The Journal of Experimental Medicine 213/6||2019-07-05|
KÃ¼ffer, Alexander; Lakkaraju, Asvin K. K.; Mogha, Amit; Petersen, Sarah C.; Airich, Kristina; Doucerain, CÃ©dric; Marpakwar, Rajlakshmi; Bakirci, Pamela; Senatore, Assunta; Monnard, Arnaud; Schiavi, Carmen; Nuvolone, Mario; Grosshans, Bianka; Hornemann, Simone; Bassilana, Frederic; Monk, Kelly R.; Aguzzi, Adriano
The prion protein is an agonistic ligand of the G protein-coupled receptor Adgrg6
published pages: , ISSN: 0028-0836, DOI: 10.5167/uzh-125485
Pfammatter, Manuela; Andreasen, Maria; Meisl, Georg; Taylor, Christopher G; Adamcik, Jozef; Bolisetty, Sreenath; Sanchez-Ferrer, Antoni; Klenerman, David; Dobson, Christopher M; Mezzenga, Raffaele; Knowles, Tuomas P J; Aguzzi, Adriano A; Hornemann, Simone
Absolute Quantification of Amyloid Propagons by Digital Microfluidics
published pages: 12306-12313, ISSN: 0003-2700, DOI: 10.5167/uzh-141180
|Analytical Chemistry 89(22)||2019-07-05|
Despoina Goniotaki, Asvin K. K. Lakkaraju, Amulya N. Shrivastava, Pamela Bakirci, Silvia Sorce, Assunta Senatore, Rajlakshmi Marpakwar, Simone Hornemann, Fabrizio Gasparini, Antoine Triller, Adriano Aguzzi
Inhibition of group-I metabotropic glutamate receptors protects against prion toxicity
published pages: e1006733, ISSN: 1553-7374, DOI: 10.1371/journal.ppat.1006733
|PLOS Pathogens 13/11||2019-07-05|
Henning Leske, Simone Hornemann, Uli Simon Herrmann, Caihong Zhu, Paolo Dametto, Bei Li, Florent Laferriere, Magdalini Polymenidou, Pawel Pelczar, Regina Rose Reimann, Petra Schwarz, Elisabeth Jane Rushing, Kurt WÃ¼thrich, Adriano Aguzzi
Protease resistance of infectious prions is suppressed by removal of a single atom in the cellular prion protein
published pages: e0170503, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0170503
|PLOS ONE 12/2||2019-07-05|
Regina R. Reimann, Tiziana Sonati, Simone Hornemann, Uli S. Herrmann, Michael Arand, Simon Hawke, Adriano Aguzzi
Differential Toxicity of Antibodies to the Prion Protein
published pages: e1005401, ISSN: 1553-7374, DOI: 10.1371/journal.ppat.1005401
|PLOS Pathogens 12/1||2019-07-05|
Reimann, Regina R; Aguzzi, Adriano
Intrinsic Toxicity of Antibodies to the Globular Domain of the Prion Protein
published pages: , ISSN: 0006-3223, DOI: 10.5167/uzh-151650
|Biological Psychiatry 12 April 2018||2019-07-05|
Adriano Aguzzi, Asvin K.K. Lakkaraju
Cell Biology of Prions and Prionoids: A Status Report
published pages: 40-51, ISSN: 0962-8924, DOI: 10.1016/j.tcb.2015.08.007
|Trends in Cell Biology 26/1||2019-07-05|
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