---
_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:
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date_created: 2021-10-27T07:45:37Z
date_updated: 2022-12-20T23:30:05Z
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file_id: '10186'
file_name: Hana_Semeradova_Disertation_Thesis_II_Revised_3.docx
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date_created: 2021-10-27T07:45:57Z
date_updated: 2022-12-20T23:30:05Z
embargo: 2022-10-28
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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
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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
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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'
...