--- _id: '10135' abstract: - lang: eng text: "Plants maintain the capacity to develop new organs e.g. lateral roots post-embryonically throughout their whole life and thereby flexibly adapt to ever-changing environmental conditions. Plant hormones auxin and cytokinin are the main regulators of the lateral root organogenesis. Additionally to their solo activities, the interaction between auxin and\r\ncytokinin plays crucial role in fine-tuning of lateral root development and growth. In particular, cytokinin modulates auxin distribution within the developing lateral root by affecting the endomembrane trafficking of auxin transporter PIN1 and promoting its vacuolar degradation (Marhavý et al., 2011, 2014). This effect is independent of transcription and\r\ntranslation. Therefore, it suggests novel, non-canonical cytokinin activity occuring possibly on the posttranslational level. Impact of cytokinin and other plant hormones on auxin transporters (including PIN1) on the posttranslational level is described in detail in the introduction part of this thesis in a form of a review (Semeradova et al., 2020). To gain insights into the molecular machinery underlying cytokinin effect on the endomembrane trafficking in the plant cell, in particular on the PIN1 degradation, we conducted two large proteomic screens: 1) Identification of cytokinin binding proteins using\r\nchemical proteomics. 2) Monitoring of proteomic and phosphoproteomic changes upon cytokinin treatment. In the first screen, we identified DYNAMIN RELATED PROTEIN 2A (DRP2A). We found that DRP2A plays a role in cytokinin regulated processes during the plant growth and that cytokinin treatment promotes destabilization of DRP2A protein. However, the role of DRP2A in the PIN1 degradation remains to be elucidated. In the second screen, we found VACUOLAR PROTEIN SORTING 9A (VPS9A). VPS9a plays crucial role in plant’s response to cytokin and in cytokinin mediated PIN1 degradation. Altogether, we identified proteins, which bind to cytokinin and proteins that in response to\r\ncytokinin exhibit significantly changed abundance or phosphorylation pattern. By combining information from these two screens, we can pave our way towards understanding of noncanonical cytokinin effects." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Hana full_name: Semerádová, Hana id: 42FE702E-F248-11E8-B48F-1D18A9856A87 last_name: Semerádová citation: ama: Semerádová H. Molecular mechanisms of the cytokinin-regulated endomembrane trafficking to coordinate plant organogenesis. 2021. doi:10.15479/at:ista:10135 apa: Semerádová, H. (2021). Molecular mechanisms of the cytokinin-regulated endomembrane trafficking to coordinate plant organogenesis. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:10135 chicago: Semerádová, Hana. “Molecular Mechanisms of the Cytokinin-Regulated Endomembrane Trafficking to Coordinate Plant Organogenesis.” Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:10135. ieee: H. Semerádová, “Molecular mechanisms of the cytokinin-regulated endomembrane trafficking to coordinate plant organogenesis,” Institute of Science and Technology Austria, 2021. ista: Semerádová H. 2021. Molecular mechanisms of the cytokinin-regulated endomembrane trafficking to coordinate plant organogenesis. Institute of Science and Technology Austria. mla: Semerádová, Hana. Molecular Mechanisms of the Cytokinin-Regulated Endomembrane Trafficking to Coordinate Plant Organogenesis. Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:10135. short: H. Semerádová, Molecular Mechanisms of the Cytokinin-Regulated Endomembrane Trafficking to Coordinate Plant Organogenesis, Institute of Science and Technology Austria, 2021. date_created: 2021-10-13T13:42:48Z date_published: 2021-10-13T00:00:00Z date_updated: 2024-01-25T10:53:29Z day: '13' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: EvBe doi: 10.15479/at:ista:10135 file: - access_level: closed checksum: ce7108853e6cec6224f17cd6429b51fe content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cziletti date_created: 2021-10-27T07:45:37Z date_updated: 2022-12-20T23:30:05Z embargo_to: open_access file_id: '10186' file_name: Hana_Semeradova_Disertation_Thesis_II_Revised_3.docx file_size: 28508629 relation: source_file - access_level: open_access checksum: 0d7afb846e8e31ec794de47bf44e12ef content_type: application/pdf creator: cziletti date_created: 2021-10-27T07:45:57Z date_updated: 2022-12-20T23:30:05Z embargo: 2022-10-28 file_id: '10187' file_name: Hana_Semeradova_Disertation_Thesis_II_Revised_3PDFA.pdf file_size: 10623525 relation: main_file file_date_updated: 2022-12-20T23:30:05Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version project: - _id: 261821BC-B435-11E9-9278-68D0E5697425 grant_number: '24746' name: Molecular mechanisms of the cytokinin regulated endomembrane trafficking to coordinate plant organogenesis. publication_identifier: isbn: - 978-3-99078-014-5 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '9160' relation: part_of_dissertation status: public status: public supervisor: - first_name: Eva full_name: Benková, Eva id: 38F4F166-F248-11E8-B48F-1D18A9856A87 last_name: Benková orcid: 0000-0002-8510-9739 title: Molecular mechanisms of the cytokinin-regulated endomembrane trafficking to coordinate plant organogenesis type: dissertation user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2021' ... --- _id: '9728' abstract: - lang: eng text: "Most real-world flows are multiphase, yet we know little about them compared to their single-phase counterparts. Multiphase flows are more difficult to investigate as their dynamics occur in large parameter space and involve complex phenomena such as preferential concentration, turbulence modulation, non-Newtonian rheology, etc. Over the last few decades, experiments in particle-laden flows have taken a back seat in favour of ever-improving computational resources. However, computers are still not powerful enough to simulate a real-world fluid with millions of finite-size particles. Experiments are essential not only because they offer a reliable way to investigate real-world multiphase flows but also because they serve to validate numerical studies and steer the research in a relevant direction. In this work, we have experimentally investigated particle-laden flows in pipes, and in particular, examined the effect of particles on the laminar-turbulent transition and the drag scaling in turbulent flows.\r\n\r\nFor particle-laden pipe flows, an earlier study [Matas et al., 2003] reported how the sub-critical (i.e., hysteretic) transition that occurs via localised turbulent structures called puffs is affected by the addition of particles. In this study, in addition to this known transition, we found a super-critical transition to a globally fluctuating state with increasing particle concentration. At the same time, the Newtonian-type transition via puffs is delayed to larger Reynolds numbers. At an even higher concentration, only the globally fluctuating state is found. The dynamics of particle-laden flows are hence determined by two competing instabilities that give rise to three flow regimes: Newtonian-type turbulence at low, a particle-induced globally fluctuating state at high, and a coexistence state at intermediate concentrations.\r\n\r\nThe effect of particles on turbulent drag is ambiguous, with studies reporting drag reduction, no net change, and even drag increase. The ambiguity arises because, in addition to particle concentration, particle shape, size, and density also affect the net drag. Even similar particles might affect the flow dissimilarly in different Reynolds number and concentration ranges. In the present study, we explored a wide range of both Reynolds number and concentration, using spherical as well as cylindrical particles. We found that the spherical particles do not reduce drag while the cylindrical particles are drag-reducing within a specific Reynolds number interval. The interval strongly depends on the particle concentration and the relative size of the pipe and particles. Within this interval, the magnitude of drag reduction reaches a maximum. These drag reduction maxima appear to fall onto a distinct power-law curve irrespective of the pipe diameter and particle concentration, and this curve can be considered as the maximum drag reduction asymptote for a given fibre shape. Such an asymptote is well known for polymeric flows but had not been identified for particle-laden flows prior to this work." acknowledged_ssus: - _id: M-Shop alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Nishchal full_name: Agrawal, Nishchal id: 469E6004-F248-11E8-B48F-1D18A9856A87 last_name: Agrawal citation: ama: Agrawal N. Transition to turbulence and drag reduction in particle-laden pipe flows. 2021. doi:10.15479/at:ista:9728 apa: Agrawal, N. (2021). Transition to turbulence and drag reduction in particle-laden pipe flows. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:9728 chicago: Agrawal, Nishchal. “Transition to Turbulence and Drag Reduction in Particle-Laden Pipe Flows.” Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:9728. ieee: N. Agrawal, “Transition to turbulence and drag reduction in particle-laden pipe flows,” Institute of Science and Technology Austria, 2021. ista: Agrawal N. 2021. Transition to turbulence and drag reduction in particle-laden pipe flows. Institute of Science and Technology Austria. mla: Agrawal, Nishchal. Transition to Turbulence and Drag Reduction in Particle-Laden Pipe Flows. Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:9728. short: N. Agrawal, Transition to Turbulence and Drag Reduction in Particle-Laden Pipe Flows, Institute of Science and Technology Austria, 2021. date_created: 2021-07-27T13:40:30Z date_published: 2021-07-29T00:00:00Z date_updated: 2024-02-28T13:14:39Z day: '29' ddc: - '532' degree_awarded: PhD department: - _id: GradSch - _id: BjHo doi: 10.15479/at:ista:9728 file: - access_level: closed checksum: 77436be3563a90435024307b1b5ee7e8 content_type: application/x-zip-compressed creator: nagrawal date_created: 2021-07-28T13:32:02Z date_updated: 2022-07-29T22:30:05Z embargo_to: open_access file_id: '9744' file_name: Transition to Turbulence and Drag Reduction in Particle-Laden Pipe Flows.zip file_size: 22859658 relation: source_file - access_level: open_access checksum: 72a891d7daba85445c29b868c22575ed content_type: application/pdf creator: nagrawal date_created: 2021-07-28T13:32:05Z date_updated: 2022-07-29T22:30:05Z embargo: 2022-07-28 file_id: '9745' file_name: Transition to Turbulence and Drag Reduction in Particle-Laden Pipe Flows.pdf file_size: 18658048 relation: main_file file_date_updated: 2022-07-29T22:30:05Z has_accepted_license: '1' keyword: - Drag Reduction - Transition to Turbulence - Multiphase Flows - particle Laden Flows - Complex Flows - Experiments - Fluid Dynamics language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '118' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6189' relation: part_of_dissertation status: public status: public supervisor: - first_name: Björn full_name: Hof, Björn id: 3A374330-F248-11E8-B48F-1D18A9856A87 last_name: Hof orcid: 0000-0003-2057-2754 title: Transition to turbulence and drag reduction in particle-laden pipe flows tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2021' ... --- _id: '10336' abstract: - lang: eng text: Biological membranes can dramatically accelerate the aggregation of normally soluble protein molecules into amyloid fibrils and alter the fibril morphologies, yet the molecular mechanisms through which this accelerated nucleation takes place are not yet understood. Here, we develop a coarse-grained model to systematically explore the effect that the structural properties of the lipid membrane and the nature of protein–membrane interactions have on the nucleation rates of amyloid fibrils. We identify two physically distinct nucleation pathways—protein-rich and lipid-rich—and quantify how the membrane fluidity and protein–membrane affinity control the relative importance of those molecular pathways. We find that the membrane’s susceptibility to reshaping and being incorporated into the fibrillar aggregates is a key determinant of its ability to promote protein aggregation. We then characterize the rates and the free-energy profile associated with this heterogeneous nucleation process, in which the surface itself participates in the aggregate structure. Finally, we compare quantitatively our data to experiments on membrane-catalyzed amyloid aggregation of α-synuclein, a protein implicated in Parkinson’s disease that predominately nucleates on membranes. More generally, our results provide a framework for understanding macromolecular aggregation on lipid membranes in a broad biological and biotechnological context. acknowledgement: We thank T. C. T. Michaels for reading the manuscript. This work was supported by the Academy of Medical Science (J.K. and A.Š.), the Cambridge Center for Misfolding Diseases (T.P.J.K.), the Biotechnology and Biological Sciences Research Council (T.P.J.K.), the Frances and Augustus Newman Foundation (T.P.J.K.), the European Research Council Grant PhysProt Agreement 337969, the Wellcome Trust (A.Š. and T.P.J.K.), the Royal Society (A.Š.), the Medical Research Council (J.K. and A.Š.), and the UK Materials and Molecular Modeling Hub for computational resources, which is partially funded by Engineering and Physical Sciences Research Council Grant EP/P020194/1. article_processing_charge: No article_type: original author: - first_name: Johannes full_name: Krausser, Johannes last_name: Krausser - first_name: Tuomas P. J. full_name: Knowles, Tuomas P. J. last_name: Knowles - first_name: Anđela full_name: Šarić, Anđela id: bf63d406-f056-11eb-b41d-f263a6566d8b last_name: Šarić orcid: 0000-0002-7854-2139 citation: ama: Krausser J, Knowles TPJ, Šarić A. Physical mechanisms of amyloid nucleation on fluid membranes. Proceedings of the National Academy of Sciences. 2020;117(52):33090-33098. doi:10.1073/pnas.2007694117 apa: Krausser, J., Knowles, T. P. J., & Šarić, A. (2020). Physical mechanisms of amyloid nucleation on fluid membranes. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.2007694117 chicago: Krausser, Johannes, Tuomas P. J. Knowles, and Anđela Šarić. “Physical Mechanisms of Amyloid Nucleation on Fluid Membranes.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2007694117. ieee: J. Krausser, T. P. J. Knowles, and A. Šarić, “Physical mechanisms of amyloid nucleation on fluid membranes,” Proceedings of the National Academy of Sciences, vol. 117, no. 52. National Academy of Sciences, pp. 33090–33098, 2020. ista: Krausser J, Knowles TPJ, Šarić A. 2020. Physical mechanisms of amyloid nucleation on fluid membranes. Proceedings of the National Academy of Sciences. 117(52), 33090–33098. mla: Krausser, Johannes, et al. “Physical Mechanisms of Amyloid Nucleation on Fluid Membranes.” Proceedings of the National Academy of Sciences, vol. 117, no. 52, National Academy of Sciences, 2020, pp. 33090–98, doi:10.1073/pnas.2007694117. short: J. Krausser, T.P.J. Knowles, A. Šarić, Proceedings of the National Academy of Sciences 117 (2020) 33090–33098. date_created: 2021-11-25T15:07:09Z date_published: 2020-12-16T00:00:00Z date_updated: 2021-11-25T15:35:58Z day: '16' doi: 10.1073/pnas.2007694117 extern: '1' external_id: pmid: - '33328273' intvolume: ' 117' issue: '52' language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/10.1101/2019.12.22.886267v2 month: '12' oa: 1 oa_version: Published Version page: 33090-33098 pmid: 1 publication: Proceedings of the National Academy of Sciences publication_identifier: eissn: - 1091-6490 issn: - 0027-8424 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' scopus_import: '1' status: public title: Physical mechanisms of amyloid nucleation on fluid membranes type: journal_article user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 volume: 117 year: '2020' ... --- _id: '10342' abstract: - lang: eng text: The blood-brain barrier is made of polarized brain endothelial cells (BECs) phenotypically conditioned by the central nervous system (CNS). Although transport across BECs is of paramount importance for nutrient uptake as well as ridding the brain of waste products, the intracellular sorting mechanisms that regulate successful receptor-mediated transcytosis in BECs remain to be elucidated. Here, we used a synthetic multivalent system with tunable avidity to the low-density lipoprotein receptor–related protein 1 (LRP1) to investigate the mechanisms of transport across BECs. We used a combination of conventional and super-resolution microscopy, both in vivo and in vitro, accompanied with biophysical modeling of transport kinetics and membrane-bound interactions to elucidate the role of membrane-sculpting protein syndapin-2 on fast transport via tubule formation. We show that high-avidity cargo biases the LRP1 toward internalization associated with fast degradation, while mid-avidity augments the formation of syndapin-2 tubular carriers promoting a fast shuttling across. acknowledgement: 'Funding: G.B. thanks the ERC for the starting grant (MEViC 278793) and consolidator award (CheSSTaG 769798), EPSRC/BTG Healthcare Partnership (EP/I001697/1), EPSRC Established Career Fellowship (EP/N026322/1), EPSRC/SomaNautix Healthcare Partnership EP/R024723/1, and Children with Cancer UK for the research project (16-227). X.T. and G.B. thank that Anhui 100 Talent program for facilitating data sharing and research visits. A.D.-C. and L.R. acknowledge the Royal Society for a Newton fellowship and the Marie Skłodowska-Curie Actions for a European Fellowship. Author contributions: X.T. prepared and characterized POs, performed all the fast imaging in both conventional and STED microscopy, set up the initial BBB model, encapsulated the PtA2 in POs, and supervised the PtA2-PO animal work. D.M.L. prepared and characterized POs; performed all the permeability studies, PLA assays, WB and associated data analysis, and part of the colocalization assays; and performed experiments with the shRNA for knockdown of syndapin-2. E.S. prepared and characterized POs and performed part of colocalization assays and Cy7-labeled PO animal experiments. S.N. prepared and characterized POs and performed part of the colocalization and inhibition assays. G.F. designed, performed, and analyzed the agent-based simulations of transcytosis. J.F. designed the image-based algorithm to analyze the PLA data. D.M. prepared and characterized POs and helped with Cy7-labeled PO animal experiments. A.A. performed TEM imaging of the POs. A.P. and A.D.-C. synthesized the dye- and peptide-functionalized and pristine copolymers. M.V., L.H.-K., and A.Š. designed, performed, and analyzed the MD simulations. Z.Z. supervised and supported STED imaging. P.X., B.F., and Y.T. synthesized and characterized the PtA2 compound. L.L. performed some of the animal work. L.R. supported and helped with the BBB characterization. G.B. analyzed all fast imaging and supervised and coordinated the overall work. X.T., D.M.L., E.S., and G.B. wrote the manuscript. Competing interests: The authors declare that part of the work is associated with the UCL spin-out company SomaNautix Ltd. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.' article_number: 'eabc4397 ' article_processing_charge: No article_type: original author: - first_name: Xiaohe full_name: Tian, Xiaohe last_name: Tian - first_name: Diana M. full_name: Leite, Diana M. last_name: Leite - first_name: Edoardo full_name: Scarpa, Edoardo last_name: Scarpa - first_name: Sophie full_name: Nyberg, Sophie last_name: Nyberg - first_name: Gavin full_name: Fullstone, Gavin last_name: Fullstone - first_name: Joe full_name: Forth, Joe last_name: Forth - first_name: Diana full_name: Matias, Diana last_name: Matias - first_name: Azzurra full_name: Apriceno, Azzurra last_name: Apriceno - first_name: Alessandro full_name: Poma, Alessandro last_name: Poma - first_name: Aroa full_name: Duro-Castano, Aroa last_name: Duro-Castano - first_name: Manish full_name: Vuyyuru, Manish last_name: Vuyyuru - first_name: Lena full_name: Harker-Kirschneck, Lena last_name: Harker-Kirschneck - first_name: Anđela full_name: Šarić, Anđela id: bf63d406-f056-11eb-b41d-f263a6566d8b last_name: Šarić orcid: 0000-0002-7854-2139 - first_name: Zhongping full_name: Zhang, Zhongping last_name: Zhang - first_name: Pan full_name: Xiang, Pan last_name: Xiang - first_name: Bin full_name: Fang, Bin last_name: Fang - first_name: Yupeng full_name: Tian, Yupeng last_name: Tian - first_name: Lei full_name: Luo, Lei last_name: Luo - first_name: Loris full_name: Rizzello, Loris last_name: Rizzello - first_name: Giuseppe full_name: Battaglia, Giuseppe last_name: Battaglia citation: ama: 'Tian X, Leite DM, Scarpa E, et al. On the shuttling across the blood-brain barrier via tubule formation: Mechanism and cargo avidity bias. Science Advances. 2020;6(48). doi:10.1126/sciadv.abc4397' apa: 'Tian, X., Leite, D. M., Scarpa, E., Nyberg, S., Fullstone, G., Forth, J., … Battaglia, G. (2020). On the shuttling across the blood-brain barrier via tubule formation: Mechanism and cargo avidity bias. Science Advances. American Association for the Advancement of Science. https://doi.org/10.1126/sciadv.abc4397' chicago: 'Tian, Xiaohe, Diana M. Leite, Edoardo Scarpa, Sophie Nyberg, Gavin Fullstone, Joe Forth, Diana Matias, et al. “On the Shuttling across the Blood-Brain Barrier via Tubule Formation: Mechanism and Cargo Avidity Bias.” Science Advances. American Association for the Advancement of Science, 2020. https://doi.org/10.1126/sciadv.abc4397.' ieee: 'X. Tian et al., “On the shuttling across the blood-brain barrier via tubule formation: Mechanism and cargo avidity bias,” Science Advances, vol. 6, no. 48. American Association for the Advancement of Science, 2020.' ista: 'Tian X, Leite DM, Scarpa E, Nyberg S, Fullstone G, Forth J, Matias D, Apriceno A, Poma A, Duro-Castano A, Vuyyuru M, Harker-Kirschneck L, Šarić A, Zhang Z, Xiang P, Fang B, Tian Y, Luo L, Rizzello L, Battaglia G. 2020. On the shuttling across the blood-brain barrier via tubule formation: Mechanism and cargo avidity bias. Science Advances. 6(48), eabc4397.' mla: 'Tian, Xiaohe, et al. “On the Shuttling across the Blood-Brain Barrier via Tubule Formation: Mechanism and Cargo Avidity Bias.” Science Advances, vol. 6, no. 48, eabc4397, American Association for the Advancement of Science, 2020, doi:10.1126/sciadv.abc4397.' short: X. Tian, D.M. Leite, E. Scarpa, S. Nyberg, G. Fullstone, J. Forth, D. Matias, A. Apriceno, A. Poma, A. Duro-Castano, M. Vuyyuru, L. Harker-Kirschneck, A. Šarić, Z. Zhang, P. Xiang, B. Fang, Y. Tian, L. Luo, L. Rizzello, G. Battaglia, Science Advances 6 (2020). date_created: 2021-11-26T06:40:28Z date_published: 2020-11-27T00:00:00Z date_updated: 2021-11-26T07:00:24Z day: '27' ddc: - '611' doi: 10.1126/sciadv.abc4397 extern: '1' external_id: pmid: - '33246953' file: - access_level: open_access checksum: 3ba2eca975930cdb0b1ce1ae876885a7 content_type: application/pdf creator: cchlebak date_created: 2021-11-26T06:50:09Z date_updated: 2021-11-26T06:50:09Z file_id: '10343' file_name: 2020_SciAdv_Tian.pdf file_size: 10381298 relation: main_file success: 1 file_date_updated: 2021-11-26T06:50:09Z has_accepted_license: '1' intvolume: ' 6' issue: '48' keyword: - multidisciplinary language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/10.1101/2020.04.04.025866v1 month: '11' oa: 1 oa_version: Published Version pmid: 1 publication: Science Advances publication_identifier: issn: - 2375-2548 publication_status: published publisher: American Association for the Advancement of Science quality_controlled: '1' scopus_import: '1' status: public title: 'On the shuttling across the blood-brain barrier via tubule formation: Mechanism and cargo avidity bias' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 volume: 6 year: '2020' ... --- _id: '10344' abstract: - lang: eng text: In this study, we investigate the role of the surface patterning of nanostructures for cell membrane reshaping. To accomplish this, we combine an evolutionary algorithm with coarse-grained molecular dynamics simulations and explore the solution space of ligand patterns on a nanoparticle that promote efficient and reliable cell uptake. Surprisingly, we find that in the regime of low ligand number the best-performing structures are characterized by ligands arranged into long one-dimensional chains that pattern the surface of the particle. We show that these chains of ligands provide particles with high rotational freedom and they lower the free energy barrier for membrane crossing. Our approach reveals a set of nonintuitive design rules that can be used to inform artificial nanoparticle construction and the search for inhibitors of viral entry. acknowledgement: We acknowledge support from EPSRC (J. C. F.), MRC (B. B. and A. Š.), the ERC StG 802960 “NEPA” (J. K. and A. Š.), the Royal Society (A. Š.), and the United Kingdom Materials and Molecular Modelling Hub for computational resources, which is partially funded by EPSRC (EP/P020194/1). article_number: '228101' article_processing_charge: No article_type: original author: - first_name: Joel C. full_name: Forster, Joel C. last_name: Forster - first_name: Johannes full_name: Krausser, Johannes last_name: Krausser - first_name: Manish R. full_name: Vuyyuru, Manish R. last_name: Vuyyuru - first_name: Buzz full_name: Baum, Buzz last_name: Baum - first_name: Anđela full_name: Šarić, Anđela id: bf63d406-f056-11eb-b41d-f263a6566d8b last_name: Šarić orcid: 0000-0002-7854-2139 citation: ama: Forster JC, Krausser J, Vuyyuru MR, Baum B, Šarić A. Exploring the design rules for efficient membrane-reshaping nanostructures. Physical Review Letters. 2020;125(22). doi:10.1103/physrevlett.125.228101 apa: Forster, J. C., Krausser, J., Vuyyuru, M. R., Baum, B., & Šarić, A. (2020). Exploring the design rules for efficient membrane-reshaping nanostructures. Physical Review Letters. American Physical Society. https://doi.org/10.1103/physrevlett.125.228101 chicago: Forster, Joel C., Johannes Krausser, Manish R. Vuyyuru, Buzz Baum, and Anđela Šarić. “Exploring the Design Rules for Efficient Membrane-Reshaping Nanostructures.” Physical Review Letters. American Physical Society, 2020. https://doi.org/10.1103/physrevlett.125.228101. ieee: J. C. Forster, J. Krausser, M. R. Vuyyuru, B. Baum, and A. Šarić, “Exploring the design rules for efficient membrane-reshaping nanostructures,” Physical Review Letters, vol. 125, no. 22. American Physical Society, 2020. ista: Forster JC, Krausser J, Vuyyuru MR, Baum B, Šarić A. 2020. Exploring the design rules for efficient membrane-reshaping nanostructures. Physical Review Letters. 125(22), 228101. mla: Forster, Joel C., et al. “Exploring the Design Rules for Efficient Membrane-Reshaping Nanostructures.” Physical Review Letters, vol. 125, no. 22, 228101, American Physical Society, 2020, doi:10.1103/physrevlett.125.228101. short: J.C. Forster, J. Krausser, M.R. Vuyyuru, B. Baum, A. Šarić, Physical Review Letters 125 (2020). date_created: 2021-11-26T07:10:43Z date_published: 2020-11-23T00:00:00Z date_updated: 2021-11-30T08:33:14Z day: '23' ddc: - '530' doi: 10.1103/physrevlett.125.228101 extern: '1' external_id: pmid: - '33315453' file: - access_level: open_access checksum: fbf2e1415e332d6add90222d60401a1d content_type: application/pdf creator: cchlebak date_created: 2021-11-26T07:16:49Z date_updated: 2021-11-26T07:16:49Z file_id: '10345' file_name: 2020_PhysRevLett_Forster.pdf file_size: 844353 relation: main_file success: 1 file_date_updated: 2021-11-26T07:16:49Z has_accepted_license: '1' intvolume: ' 125' issue: '22' language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/10.1101/2020.02.27.968149v1 month: '11' oa: 1 oa_version: Published Version pmid: 1 publication: Physical Review Letters publication_identifier: eissn: - 1079-7114 issn: - 0031-9007 publication_status: published publisher: American Physical Society quality_controlled: '1' scopus_import: '1' status: public title: Exploring the design rules for efficient membrane-reshaping nanostructures tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 volume: 125 year: '2020' ... --- _id: '10341' abstract: - lang: eng text: Tracing the motion of macromolecules, viruses, and nanoparticles adsorbed onto cell membranes is currently the most direct way of probing the complex dynamic interactions behind vital biological processes, including cell signalling, trafficking, and viral infection. The resulting trajectories are usually consistent with some type of anomalous diffusion, but the molecular origins behind the observed anomalous behaviour are usually not obvious. Here we use coarse-grained molecular dynamics simulations to help identify the physical mechanisms that can give rise to experimentally observed trajectories of nanoscopic objects moving on biological membranes. We find that diffusion on membranes of high fluidities typically results in normal diffusion of the adsorbed nanoparticle, irrespective of the concentration of receptors, receptor clustering, or multivalent interactions between the particle and membrane receptors. Gel-like membranes on the other hand result in anomalous diffusion of the particle, which becomes more pronounced at higher receptor concentrations. This anomalous diffusion is characterised by local particle trapping in the regions of high receptor concentrations and fast hopping between such regions. The normal diffusion is recovered in the limit where the gel membrane is saturated with receptors. We conclude that hindered receptor diffusivity can be a common reason behind the observed anomalous diffusion of viruses, vesicles, and nanoparticles adsorbed on cell and model membranes. Our results enable direct comparison with experiments and offer a new route for interpreting motility experiments on cell membranes. acknowledgement: We thank Jessica McQuade for her input at the start of the project. We acknowledge support from the ERASMUS Placement Programme (V. E. D.), the UCL Institute for the Physics of Living Systems (V. E. D. and A. Š.), the UCL Global Engagement Fund (L. M. C. J.), and the Royal Society (A. Š.). article_processing_charge: No article_type: original author: - first_name: V. E. full_name: Debets, V. E. last_name: Debets - first_name: L. M. C. full_name: Janssen, L. M. C. last_name: Janssen - first_name: Anđela full_name: Šarić, Anđela id: bf63d406-f056-11eb-b41d-f263a6566d8b last_name: Šarić orcid: 0000-0002-7854-2139 citation: ama: Debets VE, Janssen LMC, Šarić A. Characterising the diffusion of biological nanoparticles on fluid and cross-linked membranes. Soft Matter. 2020;16(47):10628-10639. doi:10.1039/d0sm00712a apa: Debets, V. E., Janssen, L. M. C., & Šarić, A. (2020). Characterising the diffusion of biological nanoparticles on fluid and cross-linked membranes. Soft Matter. Royal Society of Chemistry. https://doi.org/10.1039/d0sm00712a chicago: Debets, V. E., L. M. C. Janssen, and Anđela Šarić. “Characterising the Diffusion of Biological Nanoparticles on Fluid and Cross-Linked Membranes.” Soft Matter. Royal Society of Chemistry, 2020. https://doi.org/10.1039/d0sm00712a. ieee: V. E. Debets, L. M. C. Janssen, and A. Šarić, “Characterising the diffusion of biological nanoparticles on fluid and cross-linked membranes,” Soft Matter, vol. 16, no. 47. Royal Society of Chemistry, pp. 10628–10639, 2020. ista: Debets VE, Janssen LMC, Šarić A. 2020. Characterising the diffusion of biological nanoparticles on fluid and cross-linked membranes. Soft Matter. 16(47), 10628–10639. mla: Debets, V. E., et al. “Characterising the Diffusion of Biological Nanoparticles on Fluid and Cross-Linked Membranes.” Soft Matter, vol. 16, no. 47, Royal Society of Chemistry, 2020, pp. 10628–39, doi:10.1039/d0sm00712a. short: V.E. Debets, L.M.C. Janssen, A. Šarić, Soft Matter 16 (2020) 10628–10639. date_created: 2021-11-26T06:29:41Z date_published: 2020-10-06T00:00:00Z date_updated: 2021-11-26T07:00:33Z day: '06' doi: 10.1039/d0sm00712a extern: '1' external_id: pmid: - '33084724' intvolume: ' 16' issue: '47' keyword: - condensed matter physics - general chemistry language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/10.1101/2020.05.01.071761v1 month: '10' oa: 1 oa_version: Published Version page: 10628-10639 pmid: 1 publication: Soft Matter publication_identifier: issn: - 1744-683X - 1744-6848 publication_status: published publisher: Royal Society of Chemistry quality_controlled: '1' scopus_import: '1' status: public title: Characterising the diffusion of biological nanoparticles on fluid and cross-linked membranes type: journal_article user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 volume: 16 year: '2020' ... --- _id: '10346' abstract: - lang: eng text: One of the most robust examples of self-assembly in living organisms is the formation of collagen architectures. Collagen type I molecules are a crucial component of the extracellular matrix, where they self-assemble into fibrils of well-defined axial striped patterns. This striped fibrillar pattern is preserved across the animal kingdom and is important for the determination of cell phenotype, cell adhesion, and tissue regulation and signaling. The understanding of the physical processes that determine such a robust morphology of self-assembled collagen fibrils is currently almost completely missing. Here, we develop a minimal coarse-grained computational model to identify the physical principles of the assembly of collagen-mimetic molecules. We find that screened electrostatic interactions can drive the formation of collagen-like filaments of well-defined striped morphologies. The fibril axial pattern is determined solely by the distribution of charges on the molecule and is robust to the changes in protein concentration, monomer rigidity, and environmental conditions. We show that the striped fibrillar pattern cannot be easily predicted from the interactions between two monomers but is an emergent result of multibody interactions. Our results can help address collagen remodeling in diseases and aging and guide the design of collagen scaffolds for biotechnological applications. acknowledgement: We thank Melinda Duer, Patrick Mesquida, Lucy Colwell, Lucie Liu, Daan Frenkel, and Ivan Palaia for helpful discussions. We acknowledge support from the Engineering and Physical Sciences Research Council (A.E.H., L.K.D., and A.Š.), Biotechnology and Biological Sciences Research Council LIDo programme (N.G.G. and C.A.B.), the Royal Society (A.Š.), and the UK Materials and Molecular Modelling Hub for computational resources, which is partially funded by EPSRC ( EP/P020194/1). article_processing_charge: No article_type: original author: - first_name: Anne E. full_name: Hafner, Anne E. last_name: Hafner - first_name: Noemi G. full_name: Gyori, Noemi G. last_name: Gyori - first_name: Ciaran A. full_name: Bench, Ciaran A. last_name: Bench - first_name: Luke K. full_name: Davis, Luke K. last_name: Davis - first_name: Anđela full_name: Šarić, Anđela id: bf63d406-f056-11eb-b41d-f263a6566d8b last_name: Šarić orcid: 0000-0002-7854-2139 citation: ama: Hafner AE, Gyori NG, Bench CA, Davis LK, Šarić A. Modeling fibrillogenesis of collagen-mimetic molecules. Biophysical Journal. 2020;119(9):1791-1799. doi:10.1016/j.bpj.2020.09.013 apa: Hafner, A. E., Gyori, N. G., Bench, C. A., Davis, L. K., & Šarić, A. (2020). Modeling fibrillogenesis of collagen-mimetic molecules. Biophysical Journal. Cell Press. https://doi.org/10.1016/j.bpj.2020.09.013 chicago: Hafner, Anne E., Noemi G. Gyori, Ciaran A. Bench, Luke K. Davis, and Anđela Šarić. “Modeling Fibrillogenesis of Collagen-Mimetic Molecules.” Biophysical Journal. Cell Press, 2020. https://doi.org/10.1016/j.bpj.2020.09.013. ieee: A. E. Hafner, N. G. Gyori, C. A. Bench, L. K. Davis, and A. Šarić, “Modeling fibrillogenesis of collagen-mimetic molecules,” Biophysical Journal, vol. 119, no. 9. Cell Press, pp. 1791–1799, 2020. ista: Hafner AE, Gyori NG, Bench CA, Davis LK, Šarić A. 2020. Modeling fibrillogenesis of collagen-mimetic molecules. Biophysical Journal. 119(9), 1791–1799. mla: Hafner, Anne E., et al. “Modeling Fibrillogenesis of Collagen-Mimetic Molecules.” Biophysical Journal, vol. 119, no. 9, Cell Press, 2020, pp. 1791–99, doi:10.1016/j.bpj.2020.09.013. short: A.E. Hafner, N.G. Gyori, C.A. Bench, L.K. Davis, A. Šarić, Biophysical Journal 119 (2020) 1791–1799. date_created: 2021-11-26T07:27:24Z date_published: 2020-09-23T00:00:00Z date_updated: 2021-11-26T07:45:24Z day: '23' doi: 10.1016/j.bpj.2020.09.013 extern: '1' external_id: pmid: - '33049216' intvolume: ' 119' issue: '9' keyword: - biophysics language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/10.1101/2020.06.08.140061v1 month: '09' oa: 1 oa_version: Published Version page: 1791-1799 pmid: 1 publication: Biophysical Journal publication_identifier: issn: - 0006-3495 publication_status: published publisher: Cell Press quality_controlled: '1' scopus_import: '1' status: public title: Modeling fibrillogenesis of collagen-mimetic molecules type: journal_article user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 volume: 119 year: '2020' ... --- _id: '10350' abstract: - lang: eng text: The misfolding and aberrant aggregation of proteins into fibrillar structures is a key factor in some of the most prevalent human diseases, including diabetes and dementia. Low molecular weight oligomers are thought to be a central factor in the pathology of these diseases, as well as critical intermediates in the fibril formation process, and as such have received much recent attention. Moreover, on-pathway oligomeric intermediates are potential targets for therapeutic strategies aimed at interrupting the fibril formation process. However, a consistent framework for distinguishing on-pathway from off-pathway oligomers has hitherto been lacking and, in particular, no consensus definition of on- and off-pathway oligomers is available. In this paper, we argue that a non-binary definition of oligomers' contribution to fibril-forming pathways may be more informative and we suggest a quantitative framework, in which each oligomeric species is assigned a value between 0 and 1 describing its relative contribution to the formation of fibrils. First, we clarify the distinction between oligomers and fibrils, and then we use the formalism of reaction networks to develop a general definition for on-pathway oligomers, that yields meaningful classifications in the context of amyloid formation. By applying these concepts to Monte Carlo simulations of a minimal aggregating system, and by revisiting several previous studies of amyloid oligomers in light of our new framework, we demonstrate how to perform these classifications in practice. For each oligomeric species we obtain the degree to which it is on-pathway, highlighting the most effective pharmaceutical targets for the inhibition of amyloid fibril formation. acknowledgement: We are grateful to the Schiff Foundation (AJD), Peterhouse, Cambridge (TCTM), the Swiss National Science foundation (TCTM), Ramon Jenkins Fellowship, Sidney Sussex, Cambridge (GM), the Royal Society (AŠ), the Academy of Medical Sciences and Wellcome Trust (AŠ), the Danish Research Council (MK), the Lundbeck Foundation (MK), the Swedish Research Council (SL), the Wellcome Trust (TPJK), the Cambridge Centre for Misfolding Diseases (TPJK), the BBSRC (TPJK), the Frances and Augustus Newman Foundation (TPJK) for financial support. The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) through the ERC grants PhysProt (agreement no. 337969), MAMBA (agreement no. 340890) and NovoNordiskFonden (SL). article_processing_charge: No article_type: original author: - first_name: Alexander J. full_name: Dear, Alexander J. last_name: Dear - first_name: Georg full_name: Meisl, Georg last_name: Meisl - first_name: Anđela full_name: Šarić, Anđela id: bf63d406-f056-11eb-b41d-f263a6566d8b last_name: Šarić orcid: 0000-0002-7854-2139 - first_name: Thomas C. T. full_name: Michaels, Thomas C. T. last_name: Michaels - first_name: Magnus full_name: Kjaergaard, Magnus last_name: Kjaergaard - first_name: Sara full_name: Linse, Sara last_name: Linse - first_name: Tuomas P. J. full_name: Knowles, Tuomas P. J. last_name: Knowles citation: ama: Dear AJ, Meisl G, Šarić A, et al. Identification of on- and off-pathway oligomers in amyloid fibril formation. Chemical Science. 2020;11(24):6236-6247. doi:10.1039/c9sc06501f apa: Dear, A. J., Meisl, G., Šarić, A., Michaels, T. C. T., Kjaergaard, M., Linse, S., & Knowles, T. P. J. (2020). Identification of on- and off-pathway oligomers in amyloid fibril formation. Chemical Science. Royal Society of Chemistry. https://doi.org/10.1039/c9sc06501f chicago: Dear, Alexander J., Georg Meisl, Anđela Šarić, Thomas C. T. Michaels, Magnus Kjaergaard, Sara Linse, and Tuomas P. J. Knowles. “Identification of On- and off-Pathway Oligomers in Amyloid Fibril Formation.” Chemical Science. Royal Society of Chemistry, 2020. https://doi.org/10.1039/c9sc06501f. ieee: A. J. Dear et al., “Identification of on- and off-pathway oligomers in amyloid fibril formation,” Chemical Science, vol. 11, no. 24. Royal Society of Chemistry, pp. 6236–6247, 2020. ista: Dear AJ, Meisl G, Šarić A, Michaels TCT, Kjaergaard M, Linse S, Knowles TPJ. 2020. Identification of on- and off-pathway oligomers in amyloid fibril formation. Chemical Science. 11(24), 6236–6247. mla: Dear, Alexander J., et al. “Identification of On- and off-Pathway Oligomers in Amyloid Fibril Formation.” Chemical Science, vol. 11, no. 24, Royal Society of Chemistry, 2020, pp. 6236–47, doi:10.1039/c9sc06501f. short: A.J. Dear, G. Meisl, A. Šarić, T.C.T. Michaels, M. Kjaergaard, S. Linse, T.P.J. Knowles, Chemical Science 11 (2020) 6236–6247. date_created: 2021-11-26T09:08:19Z date_published: 2020-06-08T00:00:00Z date_updated: 2021-11-26T11:21:20Z day: '08' doi: 10.1039/c9sc06501f extern: '1' external_id: pmid: - '32953019' intvolume: ' 11' issue: '24' keyword: - general chemistry language: - iso: eng license: https://creativecommons.org/licenses/by-nc/3.0/ main_file_link: - open_access: '1' url: https://pubs.rsc.org/en/content/articlehtml/2020/sc/c9sc06501f month: '06' oa: 1 oa_version: Published Version page: 6236-6247 pmid: 1 publication: Chemical Science publication_identifier: eissn: - 2041-6539 issn: - 2041-6520 publication_status: published publisher: Royal Society of Chemistry quality_controlled: '1' scopus_import: '1' status: public title: Identification of on- and off-pathway oligomers in amyloid fibril formation tmp: image: /images/cc_by_nc.png legal_code_url: https://creativecommons.org/licenses/by-nc/3.0/legalcode name: Creative Commons Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0) short: CC BY-NC (3.0) type: journal_article user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 volume: 11 year: '2020' ... --- _id: '10349' abstract: - lang: eng text: Sulfolobus acidocaldarius is the closest experimentally tractable archaeal relative of eukaryotes and, despite lacking obvious cyclin-dependent kinase and cyclin homologs, has an ordered eukaryote-like cell cycle with distinct phases of DNA replication and division. Here, in exploring the mechanism of cell division in S. acidocaldarius, we identify a role for the archaeal proteasome in regulating the transition from the end of one cell cycle to the beginning of the next. Further, we identify the archaeal ESCRT-III homolog, CdvB, as a key target of the proteasome and show that its degradation triggers division by allowing constriction of the CdvB1:CdvB2 ESCRT-III division ring. These findings offer a minimal mechanism for ESCRT-III–mediated membrane remodeling and point to a conserved role for the proteasome in eukaryotic and archaeal cell cycle control. acknowledgement: "We thank the MRC LMCB at UCL for their support; the flow cytometry STP at the Francis Crick Institute for assistance, with special thanks to S. Purewal and D. Davis; C. Bertoli for mentorship\r\nand advice; J. M. Garcia-Arcos for help early on in this project; the entire Baum lab for their input throughout the project; the Albers lab for advice and reagents, with special thanks to M. Van Wolferen and S. Albers; the members of the Wellcome consortium for archaeal cytoskeleton studies for advice and comments; and J. Löwe, S. Oliferenko, M. Balasubramanian, and D. Gerlich for discussions and advice on the manuscript. N.P.R. and S.B. would like to thank N. Rzechorzek, A. Simon, and S. Anjum for discussion and advice." article_processing_charge: No article_type: original author: - first_name: Gabriel full_name: Tarrason Risa, Gabriel last_name: Tarrason Risa - first_name: Fredrik full_name: Hurtig, Fredrik last_name: Hurtig - first_name: Sian full_name: Bray, Sian last_name: Bray - first_name: Anne E. full_name: Hafner, Anne E. last_name: Hafner - first_name: Lena full_name: Harker-Kirschneck, Lena last_name: Harker-Kirschneck - first_name: Peter full_name: Faull, Peter last_name: Faull - first_name: Colin full_name: Davis, Colin last_name: Davis - first_name: Dimitra full_name: Papatziamou, Dimitra last_name: Papatziamou - first_name: Delyan R. full_name: Mutavchiev, Delyan R. last_name: Mutavchiev - first_name: Catherine full_name: Fan, Catherine last_name: Fan - first_name: Leticia full_name: Meneguello, Leticia last_name: Meneguello - first_name: Andre full_name: Arashiro Pulschen, Andre last_name: Arashiro Pulschen - first_name: Gautam full_name: Dey, Gautam last_name: Dey - first_name: Siân full_name: Culley, Siân last_name: Culley - first_name: Mairi full_name: Kilkenny, Mairi last_name: Kilkenny - first_name: Diorge P. full_name: Souza, Diorge P. last_name: Souza - first_name: Luca full_name: Pellegrini, Luca last_name: Pellegrini - first_name: Robertus A. M. full_name: de Bruin, Robertus A. M. last_name: de Bruin - first_name: Ricardo full_name: Henriques, Ricardo last_name: Henriques - first_name: Ambrosius P. full_name: Snijders, Ambrosius P. last_name: Snijders - first_name: Anđela full_name: Šarić, Anđela id: bf63d406-f056-11eb-b41d-f263a6566d8b last_name: Šarić orcid: 0000-0002-7854-2139 - first_name: Ann-Christin full_name: Lindås, Ann-Christin last_name: Lindås - first_name: Nicholas P. full_name: Robinson, Nicholas P. last_name: Robinson - first_name: Buzz full_name: Baum, Buzz last_name: Baum citation: ama: Tarrason Risa G, Hurtig F, Bray S, et al. The proteasome controls ESCRT-III–mediated cell division in an archaeon. Science. 2020;369(6504). doi:10.1126/science.aaz2532 apa: Tarrason Risa, G., Hurtig, F., Bray, S., Hafner, A. E., Harker-Kirschneck, L., Faull, P., … Baum, B. (2020). The proteasome controls ESCRT-III–mediated cell division in an archaeon. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aaz2532 chicago: Tarrason Risa, Gabriel, Fredrik Hurtig, Sian Bray, Anne E. Hafner, Lena Harker-Kirschneck, Peter Faull, Colin Davis, et al. “The Proteasome Controls ESCRT-III–Mediated Cell Division in an Archaeon.” Science. American Association for the Advancement of Science, 2020. https://doi.org/10.1126/science.aaz2532. ieee: G. Tarrason Risa et al., “The proteasome controls ESCRT-III–mediated cell division in an archaeon,” Science, vol. 369, no. 6504. American Association for the Advancement of Science, 2020. ista: Tarrason Risa G, Hurtig F, Bray S, Hafner AE, Harker-Kirschneck L, Faull P, Davis C, Papatziamou D, Mutavchiev DR, Fan C, Meneguello L, Arashiro Pulschen A, Dey G, Culley S, Kilkenny M, Souza DP, Pellegrini L, de Bruin RAM, Henriques R, Snijders AP, Šarić A, Lindås A-C, Robinson NP, Baum B. 2020. The proteasome controls ESCRT-III–mediated cell division in an archaeon. Science. 369(6504). mla: Tarrason Risa, Gabriel, et al. “The Proteasome Controls ESCRT-III–Mediated Cell Division in an Archaeon.” Science, vol. 369, no. 6504, American Association for the Advancement of Science, 2020, doi:10.1126/science.aaz2532. short: G. Tarrason Risa, F. Hurtig, S. Bray, A.E. Hafner, L. Harker-Kirschneck, P. Faull, C. Davis, D. Papatziamou, D.R. Mutavchiev, C. Fan, L. Meneguello, A. Arashiro Pulschen, G. Dey, S. Culley, M. Kilkenny, D.P. Souza, L. Pellegrini, R.A.M. de Bruin, R. Henriques, A.P. Snijders, A. Šarić, A.-C. Lindås, N.P. Robinson, B. Baum, Science 369 (2020). date_created: 2021-11-26T08:21:34Z date_published: 2020-08-07T00:00:00Z date_updated: 2021-11-26T08:58:33Z day: '07' doi: 10.1126/science.aaz2532 extern: '1' external_id: pmid: - '32764038' intvolume: ' 369' issue: '6504' keyword: - multidisciplinary language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/10.1101/774273v1 month: '08' oa: 1 oa_version: Preprint pmid: 1 publication: Science publication_identifier: eissn: - 1095-9203 issn: - 0036-8075 publication_status: published publisher: American Association for the Advancement of Science quality_controlled: '1' scopus_import: '1' status: public title: The proteasome controls ESCRT-III–mediated cell division in an archaeon type: journal_article user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 volume: 369 year: '2020' ... --- _id: '10347' abstract: - lang: eng text: Understanding the mechanism of action of compounds capable of inhibiting amyloid-fibril formation is critical to the development of potential therapeutics against protein-misfolding diseases. A fundamental challenge for progress is the range of possible target species and the disparate timescales involved, since the aggregating proteins are simultaneously the reactants, products, intermediates, and catalysts of the reaction. It is a complex problem, therefore, to choose the states of the aggregating proteins that should be bound by the compounds to achieve the most potent inhibition. We present here a comprehensive kinetic theory of amyloid-aggregation inhibition that reveals the fundamental thermodynamic and kinetic signatures characterizing effective inhibitors by identifying quantitative relationships between the aggregation and binding rate constants. These results provide general physical laws to guide the design and optimization of inhibitors of amyloid-fibril formation, revealing in particular the important role of on-rates in the binding of the inhibitors. acknowledgement: We acknowledge support from Peterhouse, Cambridge (T.C.T.M.); the Swiss National Science Foundation (T.C.T.M.); the Royal Society (A.S. and S.C.); the Academy of Medical Sciences (A.S.); Sidney Sussex College, Cambridge (G.M.); Newnham College, Cambridge (G.T.H.); the Wellcome Trust (T.P.J.K.); the Cambridge Center for Misfolding Diseases (T.P.J.K. and M.V.); the Biotechnology and Biological Sciences Research Council (T.P.J.K.); the Frances and Augustus Newman Foundation (T.P.J.K.); and the Synapsis Foundation for Alzheimer’s disease (P.A.). The research leading to these results has received funding from the European Research Council (ERC) under the European Union’s Seventh Framework Program (FP7/2007-2013) through the ERC Grant PhysProt (Agreement 337969). article_processing_charge: No article_type: original author: - first_name: Thomas C. T. full_name: Michaels, Thomas C. T. last_name: Michaels - first_name: Anđela full_name: Šarić, Anđela id: bf63d406-f056-11eb-b41d-f263a6566d8b last_name: Šarić orcid: 0000-0002-7854-2139 - first_name: Georg full_name: Meisl, Georg last_name: Meisl - first_name: Gabriella T. full_name: Heller, Gabriella T. last_name: Heller - first_name: Samo full_name: Curk, Samo last_name: Curk - first_name: Paolo full_name: Arosio, Paolo last_name: Arosio - first_name: Sara full_name: Linse, Sara last_name: Linse - first_name: Christopher M. full_name: Dobson, Christopher M. last_name: Dobson - first_name: Michele full_name: Vendruscolo, Michele last_name: Vendruscolo - first_name: Tuomas P. J. full_name: Knowles, Tuomas P. J. last_name: Knowles citation: ama: Michaels TCT, Šarić A, Meisl G, et al. Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors. Proceedings of the National Academy of Sciences. 2020;117(39):24251-24257. doi:10.1073/pnas.2006684117 apa: Michaels, T. C. T., Šarić, A., Meisl, G., Heller, G. T., Curk, S., Arosio, P., … Knowles, T. P. J. (2020). Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.2006684117 chicago: Michaels, Thomas C. T., Anđela Šarić, Georg Meisl, Gabriella T. Heller, Samo Curk, Paolo Arosio, Sara Linse, Christopher M. Dobson, Michele Vendruscolo, and Tuomas P. J. Knowles. “Thermodynamic and Kinetic Design Principles for Amyloid-Aggregation Inhibitors.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2006684117. ieee: T. C. T. Michaels et al., “Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors,” Proceedings of the National Academy of Sciences, vol. 117, no. 39. National Academy of Sciences, pp. 24251–24257, 2020. ista: Michaels TCT, Šarić A, Meisl G, Heller GT, Curk S, Arosio P, Linse S, Dobson CM, Vendruscolo M, Knowles TPJ. 2020. Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors. Proceedings of the National Academy of Sciences. 117(39), 24251–24257. mla: Michaels, Thomas C. T., et al. “Thermodynamic and Kinetic Design Principles for Amyloid-Aggregation Inhibitors.” Proceedings of the National Academy of Sciences, vol. 117, no. 39, National Academy of Sciences, 2020, pp. 24251–57, doi:10.1073/pnas.2006684117. short: T.C.T. Michaels, A. Šarić, G. Meisl, G.T. Heller, S. Curk, P. Arosio, S. Linse, C.M. Dobson, M. Vendruscolo, T.P.J. Knowles, Proceedings of the National Academy of Sciences 117 (2020) 24251–24257. date_created: 2021-11-26T07:48:27Z date_published: 2020-09-14T00:00:00Z date_updated: 2021-11-26T08:59:06Z day: '14' doi: 10.1073/pnas.2006684117 extern: '1' external_id: pmid: - '32929030' intvolume: ' 117' issue: '39' keyword: - multidisciplinary language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/10.1101/2020.02.22.960716 month: '09' oa: 1 oa_version: Published Version page: 24251-24257 pmid: 1 publication: Proceedings of the National Academy of Sciences publication_identifier: eissn: - 1091-6490 issn: - 0027-8424 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' scopus_import: '1' status: public title: Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors type: journal_article user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 volume: 117 year: '2020' ...