---
_id: '14784'
abstract:
- lang: eng
  text: The next steps of deep space exploration are manned missions to Moon and Mars.
    For safe space missions for crew members, it is important to understand the impact
    of space flight on the immune system. We studied the effects of 21 days dry immersion
    (DI) exposure on the transcriptomes of T cells isolated from blood samples of
    eight healthy volunteers. Samples were collected 7 days before DI, at day 7, 14,
    and 21 during DI, and 7 days after DI. RNA sequencing of CD3+T cells revealed
    transcriptional alterations across all time points, with most changes occurring
    14 days after DI exposure. At day 21, T cells showed evidence of adaptation with
    a transcriptional profile resembling that of 7 days before DI. At 7 days after
    DI, T cells again changed their transcriptional profile. These data suggest that
    T cells adapt by rewiring their transcriptomes in response to simulated weightlessness
    and that remodeling cues persist when reexposed to normal gravity.
acknowledgement: This work was supported by a postdoctoral fellowship from the Swedish
  Society for Medical Research to J.R., a CAPES-STINT joint grant to R.G.G. and L.S.W.,
  a PhD fellowship from Karolinska Institutet (KID) to E.D., a PhD fellowship from
  Fundação para a Ciência e a Tecnologia and European Social Fund to M.M.S.O., the
  program of fundamental research (theme 65.1) of the Institute for Biomedical Problems
  of the Russian Academy of Sciences (IBMP RAS) to A.A.S., S.M.S., V.A.S., O.V.K.,
  D.D.V., K.D.O., M.P.R., and S.A.P., the Tamkeen under the NYU Abu Dhabi Research
  Institute Award to the NYUAD Center for Genomics and Systems Biology (ADHPG-CGSB)
  to P.P., the Knut and Alice Wallenberg foundation to C.K., the Swedish National
  Space Agency to N.V.K. and L.S.W., Swedish Research Council, Gösta Fraenckel Foundation,
  and Karolinska Institutet to L.S.W.
article_number: adg1610
article_processing_charge: Yes
article_type: original
author:
- first_name: Carlos J.
  full_name: Gallardo-Dodd, Carlos J.
  last_name: Gallardo-Dodd
- first_name: Christian
  full_name: Oertlin, Christian
  last_name: Oertlin
- first_name: Julien
  full_name: Record, Julien
  last_name: Record
- first_name: Rômulo G.
  full_name: Galvani, Rômulo G.
  last_name: Galvani
- first_name: Christian
  full_name: Sommerauer, Christian
  last_name: Sommerauer
- first_name: Nikolai V.
  full_name: Kuznetsov, Nikolai V.
  last_name: Kuznetsov
- first_name: Evangelos
  full_name: Doukoumopoulos, Evangelos
  last_name: Doukoumopoulos
- first_name: Liaqat
  full_name: Ali, Liaqat
  last_name: Ali
- first_name: Mariana M. S.
  full_name: Oliveira, Mariana M. S.
  last_name: Oliveira
- first_name: Christina
  full_name: Seitz, Christina
  last_name: Seitz
- first_name: Mathias
  full_name: Percipalle, Mathias
  id: 45adb726-eb97-11eb-a6c2-c7c3d3caabe9
  last_name: Percipalle
- first_name: Tijana
  full_name: Nikić, Tijana
  last_name: Nikić
- first_name: Anastasia A.
  full_name: Sadova, Anastasia A.
  last_name: Sadova
- first_name: Sofia M.
  full_name: Shulgina, Sofia M.
  last_name: Shulgina
- first_name: Vjacheslav A.
  full_name: Shmarov, Vjacheslav A.
  last_name: Shmarov
- first_name: Olga V.
  full_name: Kutko, Olga V.
  last_name: Kutko
- first_name: Daria D.
  full_name: Vlasova, Daria D.
  last_name: Vlasova
- first_name: Kseniya D.
  full_name: Orlova, Kseniya D.
  last_name: Orlova
- first_name: Marina P.
  full_name: Rykova, Marina P.
  last_name: Rykova
- first_name: John
  full_name: Andersson, John
  last_name: Andersson
- first_name: Piergiorgio
  full_name: Percipalle, Piergiorgio
  last_name: Percipalle
- first_name: Claudia
  full_name: Kutter, Claudia
  last_name: Kutter
- first_name: Sergey A.
  full_name: Ponomarev, Sergey A.
  last_name: Ponomarev
- first_name: Lisa S.
  full_name: Westerberg, Lisa S.
  last_name: Westerberg
citation:
  ama: Gallardo-Dodd CJ, Oertlin C, Record J, et al. Exposure of volunteers to microgravity
    by dry immersion bed over 21 days results in gene expression changes and adaptation
    of T cells. <i>Science Advances</i>. 2023;9(34). doi:<a href="https://doi.org/10.1126/sciadv.adg1610">10.1126/sciadv.adg1610</a>
  apa: Gallardo-Dodd, C. J., Oertlin, C., Record, J., Galvani, R. G., Sommerauer,
    C., Kuznetsov, N. V., … Westerberg, L. S. (2023). Exposure of volunteers to microgravity
    by dry immersion bed over 21 days results in gene expression changes and adaptation
    of T cells. <i>Science Advances</i>. American Association for the Advancement
    of Science. <a href="https://doi.org/10.1126/sciadv.adg1610">https://doi.org/10.1126/sciadv.adg1610</a>
  chicago: Gallardo-Dodd, Carlos J., Christian Oertlin, Julien Record, Rômulo G. Galvani,
    Christian Sommerauer, Nikolai V. Kuznetsov, Evangelos Doukoumopoulos, et al. “Exposure
    of Volunteers to Microgravity by Dry Immersion Bed over 21 Days Results in Gene
    Expression Changes and Adaptation of T Cells.” <i>Science Advances</i>. American
    Association for the Advancement of Science, 2023. <a href="https://doi.org/10.1126/sciadv.adg1610">https://doi.org/10.1126/sciadv.adg1610</a>.
  ieee: C. J. Gallardo-Dodd <i>et al.</i>, “Exposure of volunteers to microgravity
    by dry immersion bed over 21 days results in gene expression changes and adaptation
    of T cells,” <i>Science Advances</i>, vol. 9, no. 34. American Association for
    the Advancement of Science, 2023.
  ista: Gallardo-Dodd CJ, Oertlin C, Record J, Galvani RG, Sommerauer C, Kuznetsov
    NV, Doukoumopoulos E, Ali L, Oliveira MMS, Seitz C, Percipalle M, Nikić T, Sadova
    AA, Shulgina SM, Shmarov VA, Kutko OV, Vlasova DD, Orlova KD, Rykova MP, Andersson
    J, Percipalle P, Kutter C, Ponomarev SA, Westerberg LS. 2023. Exposure of volunteers
    to microgravity by dry immersion bed over 21 days results in gene expression changes
    and adaptation of T cells. Science Advances. 9(34), adg1610.
  mla: Gallardo-Dodd, Carlos J., et al. “Exposure of Volunteers to Microgravity by
    Dry Immersion Bed over 21 Days Results in Gene Expression Changes and Adaptation
    of T Cells.” <i>Science Advances</i>, vol. 9, no. 34, adg1610, American Association
    for the Advancement of Science, 2023, doi:<a href="https://doi.org/10.1126/sciadv.adg1610">10.1126/sciadv.adg1610</a>.
  short: C.J. Gallardo-Dodd, C. Oertlin, J. Record, R.G. Galvani, C. Sommerauer, N.V.
    Kuznetsov, E. Doukoumopoulos, L. Ali, M.M.S. Oliveira, C. Seitz, M. Percipalle,
    T. Nikić, A.A. Sadova, S.M. Shulgina, V.A. Shmarov, O.V. Kutko, D.D. Vlasova,
    K.D. Orlova, M.P. Rykova, J. Andersson, P. Percipalle, C. Kutter, S.A. Ponomarev,
    L.S. Westerberg, Science Advances 9 (2023).
date_created: 2024-01-10T09:48:01Z
date_published: 2023-08-25T00:00:00Z
date_updated: 2024-01-16T09:38:58Z
day: '25'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.1126/sciadv.adg1610
external_id:
  isi:
  - '001054596800007'
  pmid:
  - '37624890'
file:
- access_level: open_access
  checksum: b9072e20e2d5d9d34d2c53319bafee41
  content_type: application/pdf
  creator: dernst
  date_created: 2024-01-16T09:35:28Z
  date_updated: 2024-01-16T09:35:28Z
  file_id: '14809'
  file_name: 2023_ScienceAdvances_GallardoDodd.pdf
  file_size: 1596639
  relation: main_file
  success: 1
file_date_updated: 2024-01-16T09:35:28Z
has_accepted_license: '1'
intvolume: '         9'
isi: 1
issue: '34'
keyword:
- Multidisciplinary
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '08'
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'
status: public
title: Exposure of volunteers to microgravity by dry immersion bed over 21 days results
  in gene expression changes and adaptation of T cells
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 9
year: '2023'
...
---
_id: '12334'
abstract:
- lang: eng
  text: Regulation of the Arp2/3 complex is required for productive nucleation of
    branched actin networks. An emerging aspect of regulation is the incorporation
    of subunit isoforms into the Arp2/3 complex. Specifically, both ArpC5 subunit
    isoforms, ArpC5 and ArpC5L, have been reported to fine-tune nucleation activity
    and branch junction stability. We have combined reverse genetics and cellular
    structural biology to describe how ArpC5 and ArpC5L differentially affect cell
    migration. Both define the structural stability of ArpC1 in branch junctions and,
    in turn, by determining protrusion characteristics, affect protein dynamics and
    actin network ultrastructure. ArpC5 isoforms also affect the positioning of members
    of the Ena/Vasodilator-stimulated phosphoprotein (VASP) family of actin filament
    elongators, which mediate ArpC5 isoform–specific effects on the actin assembly
    level. Our results suggest that ArpC5 and Ena/VASP proteins are part of a signaling
    pathway enhancing cell migration.</jats:p>
acknowledged_ssus:
- _id: ScienComp
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
acknowledgement: "We would like to thank K. von Peinen and B. Denker (Helmholtz Centre
  for Infection Research, Braunschweig, Germany) for experimental and technical assistance,
  respectively.\r\nThis research was supported by the Scientific Service Units (SSUs)
  of ISTA through resources provided by Scientific Computing (SciComp), the Life Science
  Facility (LSF), the Imaging and Optics facility (IOF), and the Electron Microscopy
  Facility (EMF). We acknowledge support from ISTA and from the Austrian Science Fund
  (FWF) (P33367) to F.K.M.S., from the Research Training Group GRK2223 and the Helmholtz
  Society to K.R,. and from the Deutsche Forschungsgemeinschaft (DFG) to J.F. and
  K.R."
article_number: add6495
article_processing_charge: No
article_type: original
author:
- first_name: Florian
  full_name: Fäßler, Florian
  id: 404F5528-F248-11E8-B48F-1D18A9856A87
  last_name: Fäßler
  orcid: 0000-0001-7149-769X
- first_name: Manjunath
  full_name: Javoor, Manjunath
  id: 305ab18b-dc7d-11ea-9b2f-b58195228ea2
  last_name: Javoor
- first_name: Julia
  full_name: Datler, Julia
  id: 3B12E2E6-F248-11E8-B48F-1D18A9856A87
  last_name: Datler
  orcid: 0000-0002-3616-8580
- first_name: Hermann
  full_name: Döring, Hermann
  last_name: Döring
- first_name: Florian
  full_name: Hofer, Florian
  id: b9d234ba-9e33-11ed-95b6-cd561df280e6
  last_name: Hofer
- first_name: Georgi A
  full_name: Dimchev, Georgi A
  id: 38C393BE-F248-11E8-B48F-1D18A9856A87
  last_name: Dimchev
  orcid: 0000-0001-8370-6161
- first_name: Victor-Valentin
  full_name: Hodirnau, Victor-Valentin
  id: 3661B498-F248-11E8-B48F-1D18A9856A87
  last_name: Hodirnau
- first_name: Jan
  full_name: Faix, Jan
  last_name: Faix
- first_name: Klemens
  full_name: Rottner, Klemens
  last_name: Rottner
- first_name: Florian KM
  full_name: Schur, Florian KM
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
citation:
  ama: Fäßler F, Javoor M, Datler J, et al. ArpC5 isoforms regulate Arp2/3 complex–dependent
    protrusion through differential Ena/VASP positioning. <i>Science Advances</i>.
    2023;9(3). doi:<a href="https://doi.org/10.1126/sciadv.add6495">10.1126/sciadv.add6495</a>
  apa: Fäßler, F., Javoor, M., Datler, J., Döring, H., Hofer, F., Dimchev, G. A.,
    … Schur, F. K. (2023). ArpC5 isoforms regulate Arp2/3 complex–dependent protrusion
    through differential Ena/VASP positioning. <i>Science Advances</i>. American Association
    for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.add6495">https://doi.org/10.1126/sciadv.add6495</a>
  chicago: Fäßler, Florian, Manjunath Javoor, Julia Datler, Hermann Döring, Florian
    Hofer, Georgi A Dimchev, Victor-Valentin Hodirnau, Jan Faix, Klemens Rottner,
    and Florian KM Schur. “ArpC5 Isoforms Regulate Arp2/3 Complex–Dependent Protrusion
    through Differential Ena/VASP Positioning.” <i>Science Advances</i>. American
    Association for the Advancement of Science, 2023. <a href="https://doi.org/10.1126/sciadv.add6495">https://doi.org/10.1126/sciadv.add6495</a>.
  ieee: F. Fäßler <i>et al.</i>, “ArpC5 isoforms regulate Arp2/3 complex–dependent
    protrusion through differential Ena/VASP positioning,” <i>Science Advances</i>,
    vol. 9, no. 3. American Association for the Advancement of Science, 2023.
  ista: Fäßler F, Javoor M, Datler J, Döring H, Hofer F, Dimchev GA, Hodirnau V-V,
    Faix J, Rottner K, Schur FK. 2023. ArpC5 isoforms regulate Arp2/3 complex–dependent
    protrusion through differential Ena/VASP positioning. Science Advances. 9(3),
    add6495.
  mla: Fäßler, Florian, et al. “ArpC5 Isoforms Regulate Arp2/3 Complex–Dependent Protrusion
    through Differential Ena/VASP Positioning.” <i>Science Advances</i>, vol. 9, no.
    3, add6495, American Association for the Advancement of Science, 2023, doi:<a
    href="https://doi.org/10.1126/sciadv.add6495">10.1126/sciadv.add6495</a>.
  short: F. Fäßler, M. Javoor, J. Datler, H. Döring, F. Hofer, G.A. Dimchev, V.-V.
    Hodirnau, J. Faix, K. Rottner, F.K. Schur, Science Advances 9 (2023).
date_created: 2023-01-23T07:26:42Z
date_published: 2023-01-20T00:00:00Z
date_updated: 2023-11-21T08:05:35Z
day: '20'
ddc:
- '570'
department:
- _id: FlSc
- _id: EM-Fac
doi: 10.1126/sciadv.add6495
external_id:
  isi:
  - '000964550100015'
file:
- access_level: open_access
  checksum: ce81a6d0b84170e5e8c62f6acfa15d9e
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-23T07:45:54Z
  date_updated: 2023-01-23T07:45:54Z
  file_id: '12335'
  file_name: 2023_ScienceAdvances_Faessler.pdf
  file_size: 1756234
  relation: main_file
  success: 1
file_date_updated: 2023-01-23T07:45:54Z
has_accepted_license: '1'
intvolume: '         9'
isi: 1
issue: '3'
keyword:
- Multidisciplinary
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
project:
- _id: 9B954C5C-BA93-11EA-9121-9846C619BF3A
  grant_number: P33367
  name: Structure and isoform diversity of the Arp2/3 complex
publication: Science Advances
publication_identifier:
  issn:
  - 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
  record:
  - id: '14562'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: ArpC5 isoforms regulate Arp2/3 complex–dependent protrusion through differential
  Ena/VASP positioning
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 9
year: '2023'
...
---
_id: '11336'
abstract:
- lang: eng
  text: The generation of a correctly-sized cerebral cortex with all-embracing neuronal
    and glial cell-type diversity critically depends on faithful radial glial progenitor
    (RGP) cell proliferation/differentiation programs. Temporal RGP lineage progression
    is regulated by Polycomb Repressive Complex 2 (PRC2) and loss of PRC2 activity
    results in severe neurogenesis defects and microcephaly. How PRC2-dependent gene
    expression instructs RGP lineage progression is unknown. Here we utilize Mosaic
    Analysis with Double Markers (MADM)-based single cell technology and demonstrate
    that PRC2 is not cell-autonomously required in neurogenic RGPs but rather acts
    at the global tissue-wide level. Conversely, cortical astrocyte production and
    maturation is cell-autonomously controlled by PRC2-dependent transcriptional regulation.
    We thus reveal highly distinct and sequential PRC2 functions in RGP lineage progression
    that are dependent on complex interplays between intrinsic and tissue-wide properties.
    In a broader context our results imply a critical role for the genetic and cellular
    niche environment in neural stem cell behavior.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: LifeSc
acknowledgement: We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and
  C. Czepe (VBCF GmbH, NGS  Unit)  and  S.  Gharagozlou  for  technical  support.  This  research  was  supported  by  the  Scientific  Service  Units  (SSU)  of  IST  Austria  through  resources  provided  by  the  Imaging  &  Optics
  Facility (IOF), Lab Support Facility (LSF), and Preclinical Facility (PCF). N.A.
  received funding   from   the   FWF   Firnberg-Programm   (T   1031).   The   work   was   supported   by   IST   institutional  funds  and  by  the  European  Research  Council  (ERC)  under  the  European  Union’s  Horizon
  2020 research and innovation program (grant agreement 725780 LinPro) to S.H.
article_number: abq1263
article_processing_charge: No
article_type: original
author:
- first_name: Nicole
  full_name: Amberg, Nicole
  id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
  last_name: Amberg
  orcid: 0000-0002-3183-8207
- first_name: Florian
  full_name: Pauler, Florian
  id: 48EA0138-F248-11E8-B48F-1D18A9856A87
  last_name: Pauler
- first_name: Carmen
  full_name: Streicher, Carmen
  id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
  last_name: Streicher
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: Amberg N, Pauler F, Streicher C, Hippenmeyer S. Tissue-wide genetic and cellular
    landscape shapes the execution of sequential PRC2 functions in neural stem cell
    lineage progression. <i>Science Advances</i>. 2022;8(44). doi:<a href="https://doi.org/10.1126/sciadv.abq1263">10.1126/sciadv.abq1263</a>
  apa: Amberg, N., Pauler, F., Streicher, C., &#38; Hippenmeyer, S. (2022). Tissue-wide
    genetic and cellular landscape shapes the execution of sequential PRC2 functions
    in neural stem cell lineage progression. <i>Science Advances</i>. American Association
    for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.abq1263">https://doi.org/10.1126/sciadv.abq1263</a>
  chicago: Amberg, Nicole, Florian Pauler, Carmen Streicher, and Simon Hippenmeyer.
    “Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential
    PRC2 Functions in Neural Stem Cell Lineage Progression.” <i>Science Advances</i>.
    American Association for the Advancement of Science, 2022. <a href="https://doi.org/10.1126/sciadv.abq1263">https://doi.org/10.1126/sciadv.abq1263</a>.
  ieee: N. Amberg, F. Pauler, C. Streicher, and S. Hippenmeyer, “Tissue-wide genetic
    and cellular landscape shapes the execution of sequential PRC2 functions in neural
    stem cell lineage progression,” <i>Science Advances</i>, vol. 8, no. 44. American
    Association for the Advancement of Science, 2022.
  ista: Amberg N, Pauler F, Streicher C, Hippenmeyer S. 2022. Tissue-wide genetic
    and cellular landscape shapes the execution of sequential PRC2 functions in neural
    stem cell lineage progression. Science Advances. 8(44), abq1263.
  mla: Amberg, Nicole, et al. “Tissue-Wide Genetic and Cellular Landscape Shapes the
    Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.”
    <i>Science Advances</i>, vol. 8, no. 44, abq1263, American Association for the
    Advancement of Science, 2022, doi:<a href="https://doi.org/10.1126/sciadv.abq1263">10.1126/sciadv.abq1263</a>.
  short: N. Amberg, F. Pauler, C. Streicher, S. Hippenmeyer, Science Advances 8 (2022).
date_created: 2022-04-26T15:04:50Z
date_published: 2022-11-01T00:00:00Z
date_updated: 2023-05-31T12:24:10Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1126/sciadv.abq1263
ec_funded: 1
file:
- access_level: open_access
  checksum: 0117023e188542082ca6693cf39e7f03
  content_type: application/pdf
  creator: patrickd
  date_created: 2023-03-21T14:18:10Z
  date_updated: 2023-03-21T14:18:10Z
  file_id: '12742'
  file_name: sciadv.abq1263.pdf
  file_size: 2973998
  relation: main_file
  success: 1
file_date_updated: 2023-03-21T14:18:10Z
has_accepted_license: '1'
intvolume: '         8'
issue: '44'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '725780'
  name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 268F8446-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: T0101031
  name: Role of Eed in neural stem cell lineage progression
publication: Science Advances
publication_identifier:
  issn:
  - 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA website
    relation: press_release
    url: https://ista.ac.at/en/news/whole-tissue-shapes-brain-development/
scopus_import: '1'
status: public
title: Tissue-wide genetic and cellular landscape shapes the execution of sequential
  PRC2 functions in neural stem cell lineage progression
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 8
year: '2022'
...
---
_id: '12253'
abstract:
- lang: eng
  text: The sculpting of germ layers during gastrulation relies on the coordinated
    migration of progenitor cells, yet the cues controlling these long-range directed
    movements remain largely unknown. While directional migration often relies on
    a chemokine gradient generated from a localized source, we find that zebrafish
    ventrolateral mesoderm is guided by a self-generated gradient of the initially
    uniformly expressed and secreted protein Toddler/ELABELA/Apela. We show that the
    Apelin receptor, which is specifically expressed in mesodermal cells, has a dual
    role during gastrulation, acting as a scavenger receptor to generate a Toddler
    gradient, and as a chemokine receptor to sense this guidance cue. Thus, we uncover
    a single receptor–based self-generated gradient as the enigmatic guidance cue
    that can robustly steer the directional migration of mesoderm through the complex
    and continuously changing environment of the gastrulating embryo.
acknowledgement: 'We thank K. Aumayer and the team of the biooptics facility at the
  Vienna Biocenter, particularly P. Pasierbek and T. Müller, for support with microscopy;
  K. Panser, C. Pribitzer, and the animal facility personnel for taking care of zebrafish;
  M. Binner and A. Bandura for help with genotyping; M. Codina Tobias for help with
  establishing the conditions for the Toddler overexpression compensation experiment;
  T. Lubiana Alves for sharing the code for scRNA-Seq analyses; the Heisenberg laboratory,
  particularly D. Pinheiro, for joint laboratory meetings, discussions on the project,
  and providing the tg(gsc:CAAX-GFP) fish line; the Raz laboratory for providing the
  Lifeact-GFP plasmid; A. Andersen, A. Schier, C.-P. Heisenberg, and E. Tanaka for
  comments on the manuscript; and the entire Pauli laboratory, particularly K. Gert
  and V. Deneke, for valuable discussions and feedback on the manuscript. Funding:
  Work in A.P.’s laboratory has been supported by the IMP, which receives institutional
  funding from Boehringer Ingelheim and the Austrian Research Promotion Agency (Headquarter
  grant FFG-852936), as well as the FWF START program (Y 1031-B28 to A.P.), the Human
  Frontier Science Program (HFSP) Career Development Award (CDA00066/2015 to A.P.)
  and Young Investigator Grant (RGY0079/2020 to A.P.), the SFB RNA-Deco (project number
  F 80 to A.P.), a Whitman Center Fellowship from the Marine Biological Laboratory
  (to A.P.), and EMBO-YIP funds (to A.P.). This work was supported by the European
  Union (European Research Council Starting Grant 851288 to E.H.). For the purpose
  of Open Access, the authors have applied a CC BY public copyright license to any
  Author Accepted Manuscript (AAM) version arising from this submission.'
article_number: eadd2488
article_processing_charge: No
article_type: original
author:
- first_name: Jessica
  full_name: Stock, Jessica
  last_name: Stock
- first_name: Tomas
  full_name: Kazmar, Tomas
  last_name: Kazmar
- first_name: Friederike
  full_name: Schlumm, Friederike
  last_name: Schlumm
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Andrea
  full_name: Pauli, Andrea
  last_name: Pauli
citation:
  ama: Stock J, Kazmar T, Schlumm F, Hannezo EB, Pauli A. A self-generated Toddler
    gradient guides mesodermal cell migration. <i>Science Advances</i>. 2022;8(37).
    doi:<a href="https://doi.org/10.1126/sciadv.add2488">10.1126/sciadv.add2488</a>
  apa: Stock, J., Kazmar, T., Schlumm, F., Hannezo, E. B., &#38; Pauli, A. (2022).
    A self-generated Toddler gradient guides mesodermal cell migration. <i>Science
    Advances</i>. American Association for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.add2488">https://doi.org/10.1126/sciadv.add2488</a>
  chicago: Stock, Jessica, Tomas Kazmar, Friederike Schlumm, Edouard B Hannezo, and
    Andrea Pauli. “A Self-Generated Toddler Gradient Guides Mesodermal Cell Migration.”
    <i>Science Advances</i>. American Association for the Advancement of Science,
    2022. <a href="https://doi.org/10.1126/sciadv.add2488">https://doi.org/10.1126/sciadv.add2488</a>.
  ieee: J. Stock, T. Kazmar, F. Schlumm, E. B. Hannezo, and A. Pauli, “A self-generated
    Toddler gradient guides mesodermal cell migration,” <i>Science Advances</i>, vol.
    8, no. 37. American Association for the Advancement of Science, 2022.
  ista: Stock J, Kazmar T, Schlumm F, Hannezo EB, Pauli A. 2022. A self-generated
    Toddler gradient guides mesodermal cell migration. Science Advances. 8(37), eadd2488.
  mla: Stock, Jessica, et al. “A Self-Generated Toddler Gradient Guides Mesodermal
    Cell Migration.” <i>Science Advances</i>, vol. 8, no. 37, eadd2488, American Association
    for the Advancement of Science, 2022, doi:<a href="https://doi.org/10.1126/sciadv.add2488">10.1126/sciadv.add2488</a>.
  short: J. Stock, T. Kazmar, F. Schlumm, E.B. Hannezo, A. Pauli, Science Advances
    8 (2022).
date_created: 2023-01-16T09:57:10Z
date_published: 2022-09-14T00:00:00Z
date_updated: 2023-08-04T09:49:59Z
day: '14'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1126/sciadv.add2488
ec_funded: 1
external_id:
  isi:
  - '000888875000009'
  pmid:
  - '36103529'
file:
- access_level: open_access
  checksum: f59cdb824e5d4221045def81f46f6c65
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-30T09:27:49Z
  date_updated: 2023-01-30T09:27:49Z
  file_id: '12444'
  file_name: 2022_ScienceAdvances_Stock.pdf
  file_size: 1636732
  relation: main_file
  success: 1
file_date_updated: 2023-01-30T09:27:49Z
has_accepted_license: '1'
intvolume: '         8'
isi: 1
issue: '37'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
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: A self-generated Toddler gradient guides mesodermal cell migration
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 8
year: '2022'
...
---
_id: '9262'
abstract:
- lang: eng
  text: Sequence-specific oligomers with predictable folding patterns, i.e., foldamers,
    provide new opportunities to mimic α-helical peptides and design inhibitors of
    protein-protein interactions. One major hurdle of this strategy is to retain the
    correct orientation of key side chains involved in protein surface recognition.
    Here, we show that the structural plasticity of a foldamer backbone may notably
    contribute to the required spatial adjustment for optimal interaction with the
    protein surface. By using oligoureas as α helix mimics, we designed a foldamer/peptide
    hybrid inhibitor of histone chaperone ASF1, a key regulator of chromatin dynamics.
    The crystal structure of its complex with ASF1 reveals a notable plasticity of
    the urea backbone, which adapts to the ASF1 surface to maintain the same binding
    interface. One additional benefit of generating ASF1 ligands with nonpeptide oligourea
    segments is the resistance to proteolysis in human plasma, which was highly improved
    compared to the cognate α-helical peptide.
acknowledgement: 'We thank the Synchrotron SOLEIL, the European Synchrotron Radiation
  Facility (ESRF), and the French Infrastructure for Integrated Structural Biology
  (FRISBI) ANR-10-INBS-05. We are particularly grateful to A. Clavier and A. Campalans
  for help in setting up and performing the cell penetration assays. Funding: Research
  was funded by the French Centre National de Recherche Scientifique (CNRS), the Commissariat
  à l’Energie Atomique (CEA), University of Bordeaux, University Paris-Saclay, and
  the Synchrotron Soleil. The project was supported by the ANR 2007 BREAKABOUND (JC-07-216078),
  2011 BIPBIP (ANR-10-BINF-0003), 2012 CHAPINHIB (ANR-12-BSV5-0022-01), 2015 CHIPSET
  (ANR-15-CE11-008-01), 2015 HIMPP2I (ANR-15-CE07-0010), and the program labeled by
  the ARC foundation 2016 PGA1*20160203953). M.B. was supported by Canceropole (Paris,
  France) and a grant for young researchers from La Ligue contre le Cancer. J.M. was
  supported by La Ligue contre le Cancer.'
article_number: eabd9153
article_processing_charge: No
article_type: original
author:
- first_name: Johanne
  full_name: Mbianda, Johanne
  last_name: Mbianda
- first_name: May M
  full_name: Bakail, May M
  id: FB3C3F8E-522F-11EA-B186-22963DDC885E
  last_name: Bakail
  orcid: 0000-0002-9592-1587
- first_name: Christophe
  full_name: André, Christophe
  last_name: André
- first_name: Gwenaëlle
  full_name: Moal, Gwenaëlle
  last_name: Moal
- first_name: Marie E.
  full_name: Perrin, Marie E.
  last_name: Perrin
- first_name: Guillaume
  full_name: Pinna, Guillaume
  last_name: Pinna
- first_name: Raphaël
  full_name: Guerois, Raphaël
  last_name: Guerois
- first_name: Francois
  full_name: Becher, Francois
  last_name: Becher
- first_name: Pierre
  full_name: Legrand, Pierre
  last_name: Legrand
- first_name: Seydou
  full_name: Traoré, Seydou
  last_name: Traoré
- first_name: Céline
  full_name: Douat, Céline
  last_name: Douat
- first_name: Gilles
  full_name: Guichard, Gilles
  last_name: Guichard
- first_name: Françoise
  full_name: Ochsenbein, Françoise
  last_name: Ochsenbein
citation:
  ama: Mbianda J, Bakail MM, André C, et al. Optimal anchoring of a foldamer inhibitor
    of ASF1 histone chaperone through backbone plasticity. <i>Science Advances</i>.
    2021;7(12). doi:<a href="https://doi.org/10.1126/sciadv.abd9153">10.1126/sciadv.abd9153</a>
  apa: Mbianda, J., Bakail, M. M., André, C., Moal, G., Perrin, M. E., Pinna, G.,
    … Ochsenbein, F. (2021). Optimal anchoring of a foldamer inhibitor of ASF1 histone
    chaperone through backbone plasticity. <i>Science Advances</i>. American Association
    for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.abd9153">https://doi.org/10.1126/sciadv.abd9153</a>
  chicago: Mbianda, Johanne, May M Bakail, Christophe André, Gwenaëlle Moal, Marie
    E. Perrin, Guillaume Pinna, Raphaël Guerois, et al. “Optimal Anchoring of a Foldamer
    Inhibitor of ASF1 Histone Chaperone through Backbone Plasticity.” <i>Science Advances</i>.
    American Association for the Advancement of Science, 2021. <a href="https://doi.org/10.1126/sciadv.abd9153">https://doi.org/10.1126/sciadv.abd9153</a>.
  ieee: J. Mbianda <i>et al.</i>, “Optimal anchoring of a foldamer inhibitor of ASF1
    histone chaperone through backbone plasticity,” <i>Science Advances</i>, vol.
    7, no. 12. American Association for the Advancement of Science, 2021.
  ista: Mbianda J, Bakail MM, André C, Moal G, Perrin ME, Pinna G, Guerois R, Becher
    F, Legrand P, Traoré S, Douat C, Guichard G, Ochsenbein F. 2021. Optimal anchoring
    of a foldamer inhibitor of ASF1 histone chaperone through backbone plasticity.
    Science Advances. 7(12), eabd9153.
  mla: Mbianda, Johanne, et al. “Optimal Anchoring of a Foldamer Inhibitor of ASF1
    Histone Chaperone through Backbone Plasticity.” <i>Science Advances</i>, vol.
    7, no. 12, eabd9153, American Association for the Advancement of Science, 2021,
    doi:<a href="https://doi.org/10.1126/sciadv.abd9153">10.1126/sciadv.abd9153</a>.
  short: J. Mbianda, M.M. Bakail, C. André, G. Moal, M.E. Perrin, G. Pinna, R. Guerois,
    F. Becher, P. Legrand, S. Traoré, C. Douat, G. Guichard, F. Ochsenbein, Science
    Advances 7 (2021).
date_created: 2021-03-22T07:14:03Z
date_published: 2021-03-19T00:00:00Z
date_updated: 2023-08-07T14:20:26Z
day: '19'
ddc:
- '570'
department:
- _id: CampIT
doi: 10.1126/sciadv.abd9153
external_id:
  isi:
  - '000633443000011'
  pmid:
  - '33741589'
file:
- access_level: open_access
  checksum: 737624cd0e630ffa7c52797a690500e3
  content_type: application/pdf
  creator: dernst
  date_created: 2021-03-22T12:49:00Z
  date_updated: 2021-03-22T12:49:00Z
  file_id: '9280'
  file_name: 2021_ScienceAdv_Mbianda.pdf
  file_size: 837156
  relation: main_file
  success: 1
file_date_updated: 2021-03-22T12:49:00Z
has_accepted_license: '1'
intvolume: '         7'
isi: 1
issue: '12'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
month: '03'
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'
status: public
title: Optimal anchoring of a foldamer inhibitor of ASF1 histone chaperone through
  backbone plasticity
tmp:
  image: /images/cc_by_nc.png
  legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
  short: CC BY-NC (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 7
year: '2021'
...
---
_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. <i>Science Advances</i>.
    2020;6(48). doi:<a href="https://doi.org/10.1126/sciadv.abc4397">10.1126/sciadv.abc4397</a>'
  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. <i>Science Advances</i>. American
    Association for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.abc4397">https://doi.org/10.1126/sciadv.abc4397</a>'
  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.” <i>Science Advances</i>.
    American Association for the Advancement of Science, 2020. <a href="https://doi.org/10.1126/sciadv.abc4397">https://doi.org/10.1126/sciadv.abc4397</a>.'
  ieee: 'X. Tian <i>et al.</i>, “On the shuttling across the blood-brain barrier via
    tubule formation: Mechanism and cargo avidity bias,” <i>Science Advances</i>,
    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.” <i>Science Advances</i>,
    vol. 6, no. 48, eabc4397, American Association for the Advancement of Science,
    2020, doi:<a href="https://doi.org/10.1126/sciadv.abc4397">10.1126/sciadv.abc4397</a>.'
  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: '8406'
abstract:
- lang: eng
  text: Coordinated conformational transitions in oligomeric enzymatic complexes modulate
    function in response to substrates and play a crucial role in enzyme inhibition
    and activation. Caseinolytic protease (ClpP) is a tetradecameric complex, which
    has emerged as a drug target against multiple pathogenic bacteria. Activation
    of different ClpPs by inhibitors has been independently reported from drug development
    efforts, but no rationale for inhibitor-induced activation has been hitherto proposed.
    Using an integrated approach that includes x-ray crystallography, solid- and solution-state
    nuclear magnetic resonance, molecular dynamics simulations, and isothermal titration
    calorimetry, we show that the proteasome inhibitor bortezomib binds to the ClpP
    active-site serine, mimicking a peptide substrate, and induces a concerted allosteric
    activation of the complex. The bortezomib-activated conformation also exhibits
    a higher affinity for its cognate unfoldase ClpX. We propose a universal allosteric
    mechanism, where substrate binding to a single subunit locks ClpP into an active
    conformation optimized for chaperone association and protein processive degradation.
article_number: eaaw3818
article_processing_charge: No
article_type: original
author:
- first_name: Jan
  full_name: Felix, Jan
  last_name: Felix
- first_name: Katharina
  full_name: Weinhäupl, Katharina
  last_name: Weinhäupl
- first_name: Christophe
  full_name: Chipot, Christophe
  last_name: Chipot
- first_name: François
  full_name: Dehez, François
  last_name: Dehez
- first_name: Audrey
  full_name: Hessel, Audrey
  last_name: Hessel
- first_name: Diego F.
  full_name: Gauto, Diego F.
  last_name: Gauto
- first_name: Cecile
  full_name: Morlot, Cecile
  last_name: Morlot
- first_name: Olga
  full_name: Abian, Olga
  last_name: Abian
- first_name: Irina
  full_name: Gutsche, Irina
  last_name: Gutsche
- first_name: Adrian
  full_name: Velazquez-Campoy, Adrian
  last_name: Velazquez-Campoy
- first_name: Paul
  full_name: Schanda, Paul
  id: 7B541462-FAF6-11E9-A490-E8DFE5697425
  last_name: Schanda
  orcid: 0000-0002-9350-7606
- first_name: Hugo
  full_name: Fraga, Hugo
  last_name: Fraga
citation:
  ama: Felix J, Weinhäupl K, Chipot C, et al. Mechanism of the allosteric activation
    of the ClpP protease machinery by substrates and active-site inhibitors. <i>Science
    Advances</i>. 2019;5(9). doi:<a href="https://doi.org/10.1126/sciadv.aaw3818">10.1126/sciadv.aaw3818</a>
  apa: Felix, J., Weinhäupl, K., Chipot, C., Dehez, F., Hessel, A., Gauto, D. F.,
    … Fraga, H. (2019). Mechanism of the allosteric activation of the ClpP protease
    machinery by substrates and active-site inhibitors. <i>Science Advances</i>. American
    Association for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.aaw3818">https://doi.org/10.1126/sciadv.aaw3818</a>
  chicago: Felix, Jan, Katharina Weinhäupl, Christophe Chipot, François Dehez, Audrey
    Hessel, Diego F. Gauto, Cecile Morlot, et al. “Mechanism of the Allosteric Activation
    of the ClpP Protease Machinery by Substrates and Active-Site Inhibitors.” <i>Science
    Advances</i>. American Association for the Advancement of Science, 2019. <a href="https://doi.org/10.1126/sciadv.aaw3818">https://doi.org/10.1126/sciadv.aaw3818</a>.
  ieee: J. Felix <i>et al.</i>, “Mechanism of the allosteric activation of the ClpP
    protease machinery by substrates and active-site inhibitors,” <i>Science Advances</i>,
    vol. 5, no. 9. American Association for the Advancement of Science, 2019.
  ista: Felix J, Weinhäupl K, Chipot C, Dehez F, Hessel A, Gauto DF, Morlot C, Abian
    O, Gutsche I, Velazquez-Campoy A, Schanda P, Fraga H. 2019. Mechanism of the allosteric
    activation of the ClpP protease machinery by substrates and active-site inhibitors.
    Science Advances. 5(9), eaaw3818.
  mla: Felix, Jan, et al. “Mechanism of the Allosteric Activation of the ClpP Protease
    Machinery by Substrates and Active-Site Inhibitors.” <i>Science Advances</i>,
    vol. 5, no. 9, eaaw3818, American Association for the Advancement of Science,
    2019, doi:<a href="https://doi.org/10.1126/sciadv.aaw3818">10.1126/sciadv.aaw3818</a>.
  short: J. Felix, K. Weinhäupl, C. Chipot, F. Dehez, A. Hessel, D.F. Gauto, C. Morlot,
    O. Abian, I. Gutsche, A. Velazquez-Campoy, P. Schanda, H. Fraga, Science Advances
    5 (2019).
date_created: 2020-09-17T10:28:36Z
date_published: 2019-09-04T00:00:00Z
date_updated: 2021-01-12T08:19:03Z
day: '04'
doi: 10.1126/sciadv.aaw3818
extern: '1'
intvolume: '         5'
issue: '9'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: ' https://doi.org/10.1126/sciadv.aaw3818'
month: '09'
oa: 1
oa_version: Published Version
publication: Science Advances
publication_identifier:
  issn:
  - 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
status: public
title: Mechanism of the allosteric activation of the ClpP protease machinery by substrates
  and active-site inhibitors
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 5
year: '2019'
...
---
_id: '7393'
abstract:
- lang: eng
  text: The study of parallel ecological divergence provides important clues to the
    operation of natural selection. Parallel divergence often occurs in heterogeneous
    environments with different kinds of environmental gradients in different locations,
    but the genomic basis underlying this process is unknown. We investigated the
    genomics of rapid parallel adaptation in the marine snail Littorina saxatilis
    in response to two independent environmental axes (crab-predation versus wave-action
    and low-shore versus high-shore). Using pooled whole-genome resequencing, we show
    that sharing of genomic regions of high differentiation between environments is
    generally low but increases at smaller spatial scales. We identify different shared
    genomic regions of divergence for each environmental axis and show that most of
    these regions overlap with candidate chromosomal inversions. Several inversion
    regions are divergent and polymorphic across many localities. We argue that chromosomal
    inversions could store shared variation that fuels rapid parallel adaptation to
    heterogeneous environments, possibly as balanced polymorphism shared by adaptive
    gene flow.
article_number: eaav9963
article_processing_charge: No
article_type: original
author:
- first_name: Hernán E.
  full_name: Morales, Hernán E.
  last_name: Morales
- first_name: Rui
  full_name: Faria, Rui
  last_name: Faria
- first_name: Kerstin
  full_name: Johannesson, Kerstin
  last_name: Johannesson
- first_name: Tomas
  full_name: Larsson, Tomas
  last_name: Larsson
- first_name: Marina
  full_name: Panova, Marina
  last_name: Panova
- first_name: Anja M
  full_name: Westram, Anja M
  id: 3C147470-F248-11E8-B48F-1D18A9856A87
  last_name: Westram
  orcid: 0000-0003-1050-4969
- first_name: Roger K.
  full_name: Butlin, Roger K.
  last_name: Butlin
citation:
  ama: 'Morales HE, Faria R, Johannesson K, et al. Genomic architecture of parallel
    ecological divergence: Beyond a single environmental contrast. <i>Science Advances</i>.
    2019;5(12). doi:<a href="https://doi.org/10.1126/sciadv.aav9963">10.1126/sciadv.aav9963</a>'
  apa: 'Morales, H. E., Faria, R., Johannesson, K., Larsson, T., Panova, M., Westram,
    A. M., &#38; Butlin, R. K. (2019). Genomic architecture of parallel ecological
    divergence: Beyond a single environmental contrast. <i>Science Advances</i>. AAAS.
    <a href="https://doi.org/10.1126/sciadv.aav9963">https://doi.org/10.1126/sciadv.aav9963</a>'
  chicago: 'Morales, Hernán E., Rui Faria, Kerstin Johannesson, Tomas Larsson, Marina
    Panova, Anja M Westram, and Roger K. Butlin. “Genomic Architecture of Parallel
    Ecological Divergence: Beyond a Single Environmental Contrast.” <i>Science Advances</i>.
    AAAS, 2019. <a href="https://doi.org/10.1126/sciadv.aav9963">https://doi.org/10.1126/sciadv.aav9963</a>.'
  ieee: 'H. E. Morales <i>et al.</i>, “Genomic architecture of parallel ecological
    divergence: Beyond a single environmental contrast,” <i>Science Advances</i>,
    vol. 5, no. 12. AAAS, 2019.'
  ista: 'Morales HE, Faria R, Johannesson K, Larsson T, Panova M, Westram AM, Butlin
    RK. 2019. Genomic architecture of parallel ecological divergence: Beyond a single
    environmental contrast. Science Advances. 5(12), eaav9963.'
  mla: 'Morales, Hernán E., et al. “Genomic Architecture of Parallel Ecological Divergence:
    Beyond a Single Environmental Contrast.” <i>Science Advances</i>, vol. 5, no.
    12, eaav9963, AAAS, 2019, doi:<a href="https://doi.org/10.1126/sciadv.aav9963">10.1126/sciadv.aav9963</a>.'
  short: H.E. Morales, R. Faria, K. Johannesson, T. Larsson, M. Panova, A.M. Westram,
    R.K. Butlin, Science Advances 5 (2019).
date_created: 2020-01-29T15:58:27Z
date_published: 2019-12-04T00:00:00Z
date_updated: 2023-09-06T15:35:56Z
day: '04'
ddc:
- '570'
department:
- _id: NiBa
doi: 10.1126/sciadv.aav9963
ec_funded: 1
external_id:
  isi:
  - '000505069600008'
  pmid:
  - '31840052'
file:
- access_level: open_access
  checksum: af99a5dcdc66c6d6102051faf3be48d8
  content_type: application/pdf
  creator: dernst
  date_created: 2020-02-03T13:33:25Z
  date_updated: 2020-07-14T12:47:57Z
  file_id: '7442'
  file_name: 2019_ScienceAdvances_Morales.pdf
  file_size: 1869449
  relation: main_file
file_date_updated: 2020-07-14T12:47:57Z
has_accepted_license: '1'
intvolume: '         5'
isi: 1
issue: '12'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 265B41B8-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '797747'
  name: Theoretical and empirical approaches to understanding Parallel Adaptation
publication: Science Advances
publication_identifier:
  issn:
  - 2375-2548
publication_status: published
publisher: AAAS
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Genomic architecture of parallel ecological divergence: Beyond a single environmental
  contrast'
tmp:
  image: /images/cc_by_nc.png
  legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
  short: CC BY-NC (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 5
year: '2019'
...
---
_id: '8437'
abstract:
- lang: eng
  text: Chaperonins are ubiquitous protein assemblies present in bacteria, eukaryota,
    and archaea, facilitating the folding of proteins, preventing protein aggregation,
    and thus participating in maintaining protein homeostasis in the cell. During
    their functional cycle, they bind unfolded client proteins inside their double
    ring structure and promote protein folding by closing the ring chamber in an adenosine
    5′-triphosphate (ATP)–dependent manner. Although the static structures of fully
    open and closed forms of chaperonins were solved by x-ray crystallography or electron
    microscopy, elucidating the mechanisms of such ATP-driven molecular events requires
    studying the proteins at the structural level under working conditions. We introduce
    an approach that combines site-specific nuclear magnetic resonance observation
    of very large proteins, enabled by advanced isotope labeling methods, with an
    in situ ATP regeneration system. Using this method, we provide functional insight
    into the 1-MDa large hsp60 chaperonin while processing client proteins and reveal
    how nucleotide binding, hydrolysis, and release control switching between closed
    and open states. While the open conformation stabilizes the unfolded state of
    client proteins, the internalization of the client protein inside the chaperonin
    cavity speeds up its functional cycle. This approach opens new perspectives to
    study structures and mechanisms of various ATP-driven biological machineries in
    the heat of action.
article_number: eaau4196
article_processing_charge: No
article_type: original
author:
- first_name: Guillaume
  full_name: Mas, Guillaume
  last_name: Mas
- first_name: Jia-Ying
  full_name: Guan, Jia-Ying
  last_name: Guan
- first_name: Elodie
  full_name: Crublet, Elodie
  last_name: Crublet
- first_name: Elisa Colas
  full_name: Debled, Elisa Colas
  last_name: Debled
- first_name: Christine
  full_name: Moriscot, Christine
  last_name: Moriscot
- first_name: Pierre
  full_name: Gans, Pierre
  last_name: Gans
- first_name: Guy
  full_name: Schoehn, Guy
  last_name: Schoehn
- first_name: Pavel
  full_name: Macek, Pavel
  last_name: Macek
- first_name: Paul
  full_name: Schanda, Paul
  id: 7B541462-FAF6-11E9-A490-E8DFE5697425
  last_name: Schanda
  orcid: 0000-0002-9350-7606
- first_name: Jerome
  full_name: Boisbouvier, Jerome
  last_name: Boisbouvier
citation:
  ama: Mas G, Guan J-Y, Crublet E, et al. Structural investigation of a chaperonin
    in action reveals how nucleotide binding regulates the functional cycle. <i>Science
    Advances</i>. 2018;4(9). doi:<a href="https://doi.org/10.1126/sciadv.aau4196">10.1126/sciadv.aau4196</a>
  apa: Mas, G., Guan, J.-Y., Crublet, E., Debled, E. C., Moriscot, C., Gans, P., …
    Boisbouvier, J. (2018). Structural investigation of a chaperonin in action reveals
    how nucleotide binding regulates the functional cycle. <i>Science Advances</i>.
    American Association for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.aau4196">https://doi.org/10.1126/sciadv.aau4196</a>
  chicago: Mas, Guillaume, Jia-Ying Guan, Elodie Crublet, Elisa Colas Debled, Christine
    Moriscot, Pierre Gans, Guy Schoehn, Pavel Macek, Paul Schanda, and Jerome Boisbouvier.
    “Structural Investigation of a Chaperonin in Action Reveals How Nucleotide Binding
    Regulates the Functional Cycle.” <i>Science Advances</i>. American Association
    for the Advancement of Science, 2018. <a href="https://doi.org/10.1126/sciadv.aau4196">https://doi.org/10.1126/sciadv.aau4196</a>.
  ieee: G. Mas <i>et al.</i>, “Structural investigation of a chaperonin in action
    reveals how nucleotide binding regulates the functional cycle,” <i>Science Advances</i>,
    vol. 4, no. 9. American Association for the Advancement of Science, 2018.
  ista: Mas G, Guan J-Y, Crublet E, Debled EC, Moriscot C, Gans P, Schoehn G, Macek
    P, Schanda P, Boisbouvier J. 2018. Structural investigation of a chaperonin in
    action reveals how nucleotide binding regulates the functional cycle. Science
    Advances. 4(9), eaau4196.
  mla: Mas, Guillaume, et al. “Structural Investigation of a Chaperonin in Action
    Reveals How Nucleotide Binding Regulates the Functional Cycle.” <i>Science Advances</i>,
    vol. 4, no. 9, eaau4196, American Association for the Advancement of Science,
    2018, doi:<a href="https://doi.org/10.1126/sciadv.aau4196">10.1126/sciadv.aau4196</a>.
  short: G. Mas, J.-Y. Guan, E. Crublet, E.C. Debled, C. Moriscot, P. Gans, G. Schoehn,
    P. Macek, P. Schanda, J. Boisbouvier, Science Advances 4 (2018).
date_created: 2020-09-18T10:04:51Z
date_published: 2018-09-19T00:00:00Z
date_updated: 2022-08-26T09:11:06Z
day: '19'
doi: 10.1126/sciadv.aau4196
extern: '1'
intvolume: '         4'
issue: '9'
language:
- iso: eng
month: '09'
oa_version: None
publication: Science Advances
publication_identifier:
  issn:
  - 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
status: public
title: Structural investigation of a chaperonin in action reveals how nucleotide binding
  regulates the functional cycle
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 4
year: '2018'
...
---
_id: '9057'
abstract:
- lang: eng
  text: Motility is a basic feature of living microorganisms, and how it works is
    often determined by environmental cues. Recent efforts have focused on developing
    artificial systems that can mimic microorganisms, in particular their self-propulsion.
    We report on the design and characterization of synthetic self-propelled particles
    that migrate upstream, known as positive rheotaxis. This phenomenon results from
    a purely physical mechanism involving the interplay between the polarity of the
    particles and their alignment by a viscous torque. We show quantitative agreement
    between experimental data and a simple model of an overdamped Brownian pendulum.
    The model notably predicts the existence of a stagnation point in a diverging
    flow. We take advantage of this property to demonstrate that our active particles
    can sense and predictably organize in an imposed flow. Our colloidal system represents
    an important step toward the realization of biomimetic microsystems with the ability
    to sense and respond to environmental changes.
article_number: e1400214
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: Jérémie A
  full_name: Palacci, Jérémie A
  id: 8fb92548-2b22-11eb-b7c1-a3f0d08d7c7d
  last_name: Palacci
  orcid: 0000-0002-7253-9465
- first_name: Stefano
  full_name: Sacanna, Stefano
  last_name: Sacanna
- first_name: Anaïs
  full_name: Abramian, Anaïs
  last_name: Abramian
- first_name: Jérémie
  full_name: Barral, Jérémie
  last_name: Barral
- first_name: Kasey
  full_name: Hanson, Kasey
  last_name: Hanson
- first_name: Alexander Y.
  full_name: Grosberg, Alexander Y.
  last_name: Grosberg
- first_name: David J.
  full_name: Pine, David J.
  last_name: Pine
- first_name: Paul M.
  full_name: Chaikin, Paul M.
  last_name: Chaikin
citation:
  ama: Palacci JA, Sacanna S, Abramian A, et al. Artificial rheotaxis. <i>Science
    Advances</i>. 2015;1(4). doi:<a href="https://doi.org/10.1126/sciadv.1400214">10.1126/sciadv.1400214</a>
  apa: Palacci, J. A., Sacanna, S., Abramian, A., Barral, J., Hanson, K., Grosberg,
    A. Y., … Chaikin, P. M. (2015). Artificial rheotaxis. <i>Science Advances</i>.
    American Association for the Advancement of Science . <a href="https://doi.org/10.1126/sciadv.1400214">https://doi.org/10.1126/sciadv.1400214</a>
  chicago: Palacci, Jérémie A, Stefano Sacanna, Anaïs Abramian, Jérémie Barral, Kasey
    Hanson, Alexander Y. Grosberg, David J. Pine, and Paul M. Chaikin. “Artificial
    Rheotaxis.” <i>Science Advances</i>. American Association for the Advancement
    of Science , 2015. <a href="https://doi.org/10.1126/sciadv.1400214">https://doi.org/10.1126/sciadv.1400214</a>.
  ieee: J. A. Palacci <i>et al.</i>, “Artificial rheotaxis,” <i>Science Advances</i>,
    vol. 1, no. 4. American Association for the Advancement of Science , 2015.
  ista: Palacci JA, Sacanna S, Abramian A, Barral J, Hanson K, Grosberg AY, Pine DJ,
    Chaikin PM. 2015. Artificial rheotaxis. Science Advances. 1(4), e1400214.
  mla: Palacci, Jérémie A., et al. “Artificial Rheotaxis.” <i>Science Advances</i>,
    vol. 1, no. 4, e1400214, American Association for the Advancement of Science ,
    2015, doi:<a href="https://doi.org/10.1126/sciadv.1400214">10.1126/sciadv.1400214</a>.
  short: J.A. Palacci, S. Sacanna, A. Abramian, J. Barral, K. Hanson, A.Y. Grosberg,
    D.J. Pine, P.M. Chaikin, Science Advances 1 (2015).
date_created: 2021-02-02T13:15:02Z
date_published: 2015-05-01T00:00:00Z
date_updated: 2023-02-23T13:47:52Z
day: '01'
ddc:
- '530'
doi: 10.1126/sciadv.1400214
extern: '1'
external_id:
  arxiv:
  - '1505.05111'
  pmid:
  - '26601175'
file:
- access_level: open_access
  checksum: b97d62433581875c1b85210c5f6ae370
  content_type: application/pdf
  creator: cziletti
  date_created: 2021-02-02T13:22:19Z
  date_updated: 2021-02-02T13:22:19Z
  file_id: '9058'
  file_name: 2015_ScienceAdvances_Palacci.pdf
  file_size: 2416780
  relation: main_file
  success: 1
file_date_updated: 2021-02-02T13:22:19Z
has_accepted_license: '1'
intvolume: '         1'
issue: '4'
language:
- iso: eng
month: '05'
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: Artificial rheotaxis
tmp:
  image: /images/cc_by_nc.png
  legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
  short: CC BY-NC (4.0)
type: journal_article
user_id: D865714E-FA4E-11E9-B85B-F5C5E5697425
volume: 1
year: '2015'
...
