---
_id: '15072'
abstract:
- lang: eng
text: The interaction among fundamental particles in nature leads to many interesting
effects in quantum statistical mechanics; examples include superconductivity for
charged systems and superfluidity in cold gases. It is a huge challenge for mathematical
physics to understand the collective behavior of systems containing a large number
of particles, emerging from known microscopic interactions. In this workshop we
brought together researchers working on different aspects of many-body quantum
mechanics to discuss recent developments, exchange ideas and propose new challenges
and research directions.
article_processing_charge: No
article_type: original
author:
- first_name: Christian
full_name: Hainzl, Christian
last_name: Hainzl
- first_name: Benjamin
full_name: Schlein, Benjamin
last_name: Schlein
- first_name: Robert
full_name: Seiringer, Robert
id: 4AFD0470-F248-11E8-B48F-1D18A9856A87
last_name: Seiringer
orcid: 0000-0002-6781-0521
- first_name: Simone
full_name: Warzel, Simone
last_name: Warzel
citation:
ama: Hainzl C, Schlein B, Seiringer R, Warzel S. Many-body quantum systems. Oberwolfach
Reports. 2020;16(3):2541-2603. doi:10.4171/owr/2019/41
apa: Hainzl, C., Schlein, B., Seiringer, R., & Warzel, S. (2020). Many-body
quantum systems. Oberwolfach Reports. European Mathematical Society. https://doi.org/10.4171/owr/2019/41
chicago: Hainzl, Christian, Benjamin Schlein, Robert Seiringer, and Simone Warzel.
“Many-Body Quantum Systems.” Oberwolfach Reports. European Mathematical
Society, 2020. https://doi.org/10.4171/owr/2019/41.
ieee: C. Hainzl, B. Schlein, R. Seiringer, and S. Warzel, “Many-body quantum systems,”
Oberwolfach Reports, vol. 16, no. 3. European Mathematical Society, pp.
2541–2603, 2020.
ista: Hainzl C, Schlein B, Seiringer R, Warzel S. 2020. Many-body quantum systems.
Oberwolfach Reports. 16(3), 2541–2603.
mla: Hainzl, Christian, et al. “Many-Body Quantum Systems.” Oberwolfach Reports,
vol. 16, no. 3, European Mathematical Society, 2020, pp. 2541–603, doi:10.4171/owr/2019/41.
short: C. Hainzl, B. Schlein, R. Seiringer, S. Warzel, Oberwolfach Reports 16 (2020)
2541–2603.
date_created: 2024-03-04T11:46:12Z
date_published: 2020-09-10T00:00:00Z
date_updated: 2024-03-12T12:02:00Z
day: '10'
department:
- _id: RoSe
doi: 10.4171/owr/2019/41
intvolume: ' 16'
issue: '3'
language:
- iso: eng
month: '09'
oa_version: None
page: 2541-2603
publication: Oberwolfach Reports
publication_identifier:
issn:
- 1660-8933
publication_status: published
publisher: European Mathematical Society
quality_controlled: '1'
status: public
title: Many-body quantum systems
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2020'
...
---
_id: '15071'
abstract:
- lang: eng
text: "A mesophilic methanogenic culture, designated JL01, was isolated from Holocene
permafrost in the Russian Arctic [1]. After long-term extensive cultivation at
15°C it turned out to be a tied binary culture of archaeal (JL01) and bacterial
(Sphaerochaeta associata GLS2) strains.\r\nStrain JL01 was a strict anaerobe and
grew on methanol, acetate and methylamines as energy and carbon sources. Cells
were irregular coccoid, non-motile, non-spore-forming, and Gram-stainpositive.
Optimum conditions for growth were 24-28 oC, pH 6.8–7.3 and 0.075-0.1 M NaCl.\r\nPhylogenetic
tree reconstructions based on 16S rRNA and concatenated alignment of broadly\r\nconserved
protein-coding genes revealed its close relation to Methanosarcina mazei S-6\r\nT
(similarity 99.5%). The comparison of whole genomic sequences (ANI) of the isolate
and the type strain of M.mazei was 98.5%, which is higher than the values recommended
for new species. Thus strain JL01 (=VKM B-2370=JCM 31898) represents the first
M. mazei isolated from permanently subzero Arcticsediments. The long-term co-cultivation
of JL01 with S. associata GLS2T showed the methane production without any additional
carbon and energy sources. Genome analysis of S. associata GLS2T revealed putative
genes involved in methanochondroithin catabolism."
acknowledgement: "The work was supported by of Russian Foundation of Basic Research:
grant № 19-04-00831 for Viktoria Shcherbakova and Olga Troshina, grant № 18-34-00334
for Viktoriia Oshurkova and Vladimir Trubitsyn. \r\nWe thank Dr Natalia Suzina (IBPM
RAS, Federal Research Center Pushchino Center for\r\nBiological Research RAS) for
the help with the microscopic studies, respectively; Dr. Margarita Meyer (Division
of Genetics, Department of Medicine, BWH and HMS, USA) and Dr Fedor Kondrashov (IST,
Austria) for their help in obtaining the genomic sequence of strain JL01. "
article_processing_charge: Yes
author:
- first_name: Viktoriia
full_name: Oshurkova, Viktoriia
last_name: Oshurkova
- first_name: Olga
full_name: Troshina, Olga
last_name: Troshina
- first_name: Vladimir
full_name: Trubitsyn, Vladimir
last_name: Trubitsyn
- first_name: Yana
full_name: Ryzhmanova, Yana
last_name: Ryzhmanova
- first_name: Olga
full_name: Bochkareva, Olga
id: C4558D3C-6102-11E9-A62E-F418E6697425
last_name: Bochkareva
orcid: 0000-0003-1006-6639
- first_name: Viktoria
full_name: Shcherbakova, Viktoria
last_name: Shcherbakova
citation:
ama: 'Oshurkova V, Troshina O, Trubitsyn V, Ryzhmanova Y, Bochkareva O, Shcherbakova
V. Characterization of methanosarcina mazei JL01 isolated from holocene arctic
permafrost and study of the archaeon cooperation with bacterium Sphaerochaeta
associata GLS2T. In: Proceedings of 1st International Electronic Conference
on Microbiology. MDPI; 2020. doi:10.3390/ecm2020-07116'
apa: 'Oshurkova, V., Troshina, O., Trubitsyn, V., Ryzhmanova, Y., Bochkareva, O.,
& Shcherbakova, V. (2020). Characterization of methanosarcina mazei JL01 isolated
from holocene arctic permafrost and study of the archaeon cooperation with bacterium
Sphaerochaeta associata GLS2T. In Proceedings of 1st International Electronic
Conference on Microbiology. Virtual: MDPI. https://doi.org/10.3390/ecm2020-07116'
chicago: Oshurkova, Viktoriia, Olga Troshina, Vladimir Trubitsyn, Yana Ryzhmanova,
Olga Bochkareva, and Viktoria Shcherbakova. “Characterization of Methanosarcina
Mazei JL01 Isolated from Holocene Arctic Permafrost and Study of the Archaeon
Cooperation with Bacterium Sphaerochaeta Associata GLS2T.” In Proceedings of
1st International Electronic Conference on Microbiology. MDPI, 2020. https://doi.org/10.3390/ecm2020-07116.
ieee: V. Oshurkova, O. Troshina, V. Trubitsyn, Y. Ryzhmanova, O. Bochkareva, and
V. Shcherbakova, “Characterization of methanosarcina mazei JL01 isolated from
holocene arctic permafrost and study of the archaeon cooperation with bacterium
Sphaerochaeta associata GLS2T,” in Proceedings of 1st International Electronic
Conference on Microbiology, Virtual, 2020.
ista: 'Oshurkova V, Troshina O, Trubitsyn V, Ryzhmanova Y, Bochkareva O, Shcherbakova
V. 2020. Characterization of methanosarcina mazei JL01 isolated from holocene
arctic permafrost and study of the archaeon cooperation with bacterium Sphaerochaeta
associata GLS2T. Proceedings of 1st International Electronic Conference on Microbiology.
ECM: Electronic Conference on Microbiology.'
mla: Oshurkova, Viktoriia, et al. “Characterization of Methanosarcina Mazei JL01
Isolated from Holocene Arctic Permafrost and Study of the Archaeon Cooperation
with Bacterium Sphaerochaeta Associata GLS2T.” Proceedings of 1st International
Electronic Conference on Microbiology, MDPI, 2020, doi:10.3390/ecm2020-07116.
short: V. Oshurkova, O. Troshina, V. Trubitsyn, Y. Ryzhmanova, O. Bochkareva, V.
Shcherbakova, in:, Proceedings of 1st International Electronic Conference on Microbiology,
MDPI, 2020.
conference:
end_date: 2020-11-30
location: Virtual
name: 'ECM: Electronic Conference on Microbiology'
start_date: 2020-11-02
date_created: 2024-03-04T11:41:31Z
date_published: 2020-11-02T00:00:00Z
date_updated: 2024-03-20T08:06:22Z
day: '02'
ddc:
- '570'
department:
- _id: FyKo
doi: 10.3390/ecm2020-07116
file:
- access_level: open_access
checksum: d1914af7811a21a4b2744eb51b5834e3
content_type: application/pdf
creator: dernst
date_created: 2024-03-20T08:05:46Z
date_updated: 2024-03-20T08:05:46Z
file_id: '15127'
file_name: 2020_ECM_Oshurkova.pdf
file_size: 595543
relation: main_file
success: 1
file_date_updated: 2024-03-20T08:05:46Z
has_accepted_license: '1'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
publication: Proceedings of 1st International Electronic Conference on Microbiology
publication_status: published
publisher: MDPI
quality_controlled: '1'
status: public
title: Characterization of methanosarcina mazei JL01 isolated from holocene arctic
permafrost and study of the archaeon cooperation with bacterium Sphaerochaeta associata
GLS2T
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: conference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '7525'
abstract:
- lang: eng
text: "The medial habenula (MHb) is an evolutionary conserved epithalamic structure
important for the modulation of emotional memory. It is involved in regulation
of anxiety, compulsive behavior, addiction (nicotinic and opioid), sexual and
feeding behavior. MHb receives inputs from septal regions and projects exclusively
to the interpeduncular nucleus (IPN). Distinct sub-regions of the septum project
to different subnuclei of MHb: the bed nucleus of anterior commissure projects
to dorsal MHb and the triangular septum projects to ventral MHb. Furthermore,
the dorsal and ventral MHb project to the lateral and rostral/central IPN, respectively.
Importantly, these projections have unique features of prominent co-release of
different neurotransmitters and requirement of a peculiar type of calcium channel
for release. In general, synaptic neurotransmission requires an activity-dependent
influx of Ca2+ into the presynaptic terminal through voltage-gated calcium channels.
The calcium channel family most commonly involved in neurotransmitter release
comprises three members, P/Q-, N- and R-type with Cav2.1, Cav2.2 and Cav2.3 subunits,
respectively. In contrast to most CNS synapses that mainly express Cav2.1 and/or
Cav2.2, MHb terminals in the IPN exclusively express Cav2.3. In other parts of
the brain, such as the hippocampus, Cav2.3 is mostly located to postsynaptic elements.
This unusual presynaptic location of Cav2.3 in the MHb-IPN pathway implies unique
mechanisms of glutamate release in this pathway. One potential example of such
uniqueness is the facilitation of release by GABAB receptor (GBR) activation.
Presynaptic GBRs usually inhibit the release of neurotransmitters by inhibiting
presynaptic calcium channels. MHb shows the highest expression levels of GBR in
the brain. GBRs comprise two subunits, GABAB1 (GB1) and GABAB2 (GB2), and are
associated with auxiliary subunits, called potassium channel tetramerization domain
containing proteins (KCTD) 8, 12, 12b and 16. Among these four subunits, KCTD12b
is exclusively expressed in ventral MHb, and KCTD8 shows the strongest expression
in the whole MHb among other brain regions, indicating that KCTD8 and KCTD12b
may be involved in the unique mechanisms of neurotransmitter release mediated
by Cav2.3 and regulated by GBRs in this pathway. \r\nIn the present study, we
first verified that neurotransmission in both dorsal and ventral MHb-IPN pathways
is mainly mediated by Cav2.3 using a selective blocker of R-type channels, SNX-482.
We next found that baclofen, a GBR agonist, has facilitatory effects on release
from ventral MHb terminal in rostral IPN, whereas it has inhibitory effects on
release from dorsal MHb terminals in lateral IPN, indicating that KCTD12b expressed
exclusively in ventral MHb may have a role in the facilitatory effects of GBR
activation. In a heterologous expression system using HEK cells, we found that
KCTD8 and KCTD12b but not KCTD12 directly bind with Cav2.3. Pre-embedding immunogold
electron microscopy data show that Cav2.3 and KCTD12b are distributed most densely
in presynaptic active zone in IPN with KCTD12b being present only in rostral/central
but not lateral IPN, whereas GABAB, KCTD8 and KCTD12 are distributed most densely
in perisynaptic sites with KCTD12 present more frequently in postsynaptic elements
and only in rostral/central IPN. In freeze-fracture replica labelling, Cav2.3,
KCTD8 and KCTD12b are co-localized with each other in the same active zone indicating
that they may form complexes regulating vesicle release in rostral IPN. \r\nOn
electrophysiological studies of wild type (WT) mice, we found that paired-pulse
ratio in rostral IPN of KCTD12b knock-out (KO) mice is lower than those of WT
and KCTD8 KO mice. Consistent with this finding, in mean variance analysis, release
probability in rostral IPN of KCTD12b KO mice is higher than that of WT and KCTD8
KO mice. Although paired-pulse ratios are not different between WT and KCTD8 KO
mice, the mean variance analysis revealed significantly lower release probability
in rostral IPN of KCTD8 KO than WT mice. These results demonstrate bidirectional
regulation of Cav2.3-mediated release by KCTD8 and KCTD12b without GBR activation
in rostral IPN. Finally, we examined the baclofen effects in rostral IPN of KCTD8
and KCTD12b KO mice, and found the facilitation of release remained in both KO
mice, indicating that the peculiar effects of the GBR activation in this pathway
do not depend on the selective expression of these KCTD subunits in ventral MHb.
However, we found that presynaptic potentiation of evoked EPSC amplitude by baclofen
falls to baseline after washout faster in KCTD12b KO mice than WT, KCTD8 KO and
KCTD8/12b double KO mice. This result indicates that KCTD12b is involved in sustained
potentiation of vesicle release by GBR activation, whereas KCTD8 is involved in
its termination in the absence of KCTD12b. Consistent with these functional findings,
replica labelling revealed an increase in density of KCTD8, but not Cav2.3 or
GBR at active zone in rostral IPN of KCTD12b KO mice compared with that of WT
mice, suggesting that increased association of KCTD8 with Cav2.3 facilitates the
release probability and termination of the GBR effect in the absence of KCTD12b.\r\nIn
summary, our study provided new insights into the physiological roles of presynaptic
Cav2.3, GBRs and their auxiliary subunits KCTDs at an evolutionary conserved neuronal
circuit. Future studies will be required to identify the exact molecular mechanism
underlying the GBR-mediated presynaptic potentiation on ventral MHb terminals.
It remains to be determined whether the prominent presence of presynaptic KCTDs
at active zone could exert similar neuromodulatory functions in different pathways
of the brain.\r\n"
acknowledged_ssus:
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Pradeep
full_name: Bhandari, Pradeep
id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
last_name: Bhandari
orcid: 0000-0003-0863-4481
citation:
ama: Bhandari P. Localization and functional role of Cav2.3 in the medial habenula
to interpeduncular nucleus pathway. 2020. doi:10.15479/AT:ISTA:7525
apa: Bhandari, P. (2020). Localization and functional role of Cav2.3 in the medial
habenula to interpeduncular nucleus pathway. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT:ISTA:7525
chicago: Bhandari, Pradeep. “Localization and Functional Role of Cav2.3 in the Medial
Habenula to Interpeduncular Nucleus Pathway.” Institute of Science and Technology
Austria, 2020. https://doi.org/10.15479/AT:ISTA:7525.
ieee: P. Bhandari, “Localization and functional role of Cav2.3 in the medial habenula
to interpeduncular nucleus pathway,” Institute of Science and Technology Austria,
2020.
ista: Bhandari P. 2020. Localization and functional role of Cav2.3 in the medial
habenula to interpeduncular nucleus pathway. Institute of Science and Technology
Austria.
mla: Bhandari, Pradeep. Localization and Functional Role of Cav2.3 in the Medial
Habenula to Interpeduncular Nucleus Pathway. Institute of Science and Technology
Austria, 2020, doi:10.15479/AT:ISTA:7525.
short: P. Bhandari, Localization and Functional Role of Cav2.3 in the Medial Habenula
to Interpeduncular Nucleus Pathway, Institute of Science and Technology Austria,
2020.
date_created: 2020-02-26T10:56:37Z
date_published: 2020-02-28T00:00:00Z
date_updated: 2023-09-07T13:20:03Z
day: '28'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: RySh
doi: 10.15479/AT:ISTA:7525
file:
- access_level: open_access
checksum: 4589234fdb12b4ad72273b311723a7b4
content_type: application/pdf
creator: pbhandari
date_created: 2020-02-28T08:37:53Z
date_updated: 2021-03-01T23:30:04Z
embargo: 2021-02-28
file_id: '7538'
file_name: Pradeep Bhandari Thesis.pdf
file_size: 9646346
relation: main_file
title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
nucleus pathway
- access_level: closed
checksum: aa79490553ca0a5c9b6fbcd152e93928
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: pbhandari
date_created: 2020-02-28T08:47:14Z
date_updated: 2021-03-01T23:30:04Z
embargo_to: open_access
file_id: '7539'
file_name: Pradeep Bhandari Thesis.docx
file_size: 35252164
relation: source_file
title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
nucleus pathway
file_date_updated: 2021-03-01T23:30:04Z
has_accepted_license: '1'
keyword:
- Cav2.3
- medial habenula (MHb)
- interpeduncular nucleus (IPN)
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: '79'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
nucleus pathway
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '8586'
abstract:
- lang: eng
text: Cryo-electron microscopy (cryo-EM) of cellular specimens provides insights
into biological processes and structures within a native context. However, a major
challenge still lies in the efficient and reproducible preparation of adherent
cells for subsequent cryo-EM analysis. This is due to the sensitivity of many
cellular specimens to the varying seeding and culturing conditions required for
EM experiments, the often limited amount of cellular material and also the fragility
of EM grids and their substrate. Here, we present low-cost and reusable 3D printed
grid holders, designed to improve specimen preparation when culturing challenging
cellular samples directly on grids. The described grid holders increase cell culture
reproducibility and throughput, and reduce the resources required for cell culturing.
We show that grid holders can be integrated into various cryo-EM workflows, including
micro-patterning approaches to control cell seeding on grids, and for generating
samples for cryo-focused ion beam milling and cryo-electron tomography experiments.
Their adaptable design allows for the generation of specialized grid holders customized
to a large variety of applications.
acknowledged_ssus:
- _id: ScienComp
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
acknowledgement: This work was supported by the Austrian Science Fund (FWF, P33367)
to FKMS. BZ acknowledges support by the Niederösterreich Fond. This research was
also supported by the Scientific Service Units (SSU) of IST Austria through resources
provided by Scientific Computing (SciComp), the Life Science Facility (LSF), the
BioImaging Facility (BIF) and the Electron Microscopy Facility (EMF). We thank Georgi
Dimchev (IST Austria) and Sonja Jacob (Vienna Biocenter Core Facilities) for testing
our grid holders in different experimental setups and Daniel Gütl and the Kondrashov
group (IST Austria) for granting us repeated access to their 3D printers. We also
thank Jonna Alanko and the Sixt lab (IST Austria) for providing us HeLa cells, primary
BL6 mouse tail fibroblasts, NIH 3T3 fibroblasts and human telomerase immortalised
foreskin fibroblasts for our experiments. We are thankful to Ori Avinoam and William
Wan for helpful comments on the manuscript and also thank Dorotea Fracchiolla (Art&Science)
for illustrating the graphical abstract.
article_number: '107633'
article_processing_charge: Yes (via OA deal)
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: Bettina
full_name: Zens, Bettina
id: 45FD126C-F248-11E8-B48F-1D18A9856A87
last_name: Zens
orcid: 0000-0002-9561-1239
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- 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, Zens B, Hauschild R, Schur FK. 3D printed cell culture grid holders
for improved cellular specimen preparation in cryo-electron microscopy. Journal
of Structural Biology. 2020;212(3). doi:10.1016/j.jsb.2020.107633
apa: Fäßler, F., Zens, B., Hauschild, R., & Schur, F. K. (2020). 3D printed
cell culture grid holders for improved cellular specimen preparation in cryo-electron
microscopy. Journal of Structural Biology. Elsevier. https://doi.org/10.1016/j.jsb.2020.107633
chicago: Fäßler, Florian, Bettina Zens, Robert Hauschild, and Florian KM Schur.
“3D Printed Cell Culture Grid Holders for Improved Cellular Specimen Preparation
in Cryo-Electron Microscopy.” Journal of Structural Biology. Elsevier,
2020. https://doi.org/10.1016/j.jsb.2020.107633.
ieee: F. Fäßler, B. Zens, R. Hauschild, and F. K. Schur, “3D printed cell culture
grid holders for improved cellular specimen preparation in cryo-electron microscopy,”
Journal of Structural Biology, vol. 212, no. 3. Elsevier, 2020.
ista: Fäßler F, Zens B, Hauschild R, Schur FK. 2020. 3D printed cell culture grid
holders for improved cellular specimen preparation in cryo-electron microscopy.
Journal of Structural Biology. 212(3), 107633.
mla: Fäßler, Florian, et al. “3D Printed Cell Culture Grid Holders for Improved
Cellular Specimen Preparation in Cryo-Electron Microscopy.” Journal of Structural
Biology, vol. 212, no. 3, 107633, Elsevier, 2020, doi:10.1016/j.jsb.2020.107633.
short: F. Fäßler, B. Zens, R. Hauschild, F.K. Schur, Journal of Structural Biology
212 (2020).
date_created: 2020-09-29T13:24:06Z
date_published: 2020-12-01T00:00:00Z
date_updated: 2024-03-27T23:30:05Z
day: '01'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.1016/j.jsb.2020.107633
external_id:
isi:
- '000600997800008'
file:
- access_level: open_access
checksum: c48cbf594e84fc2f91966ffaafc0918c
content_type: application/pdf
creator: dernst
date_created: 2020-12-10T14:01:10Z
date_updated: 2020-12-10T14:01:10Z
file_id: '8937'
file_name: 2020_JourStrucBiology_Faessler.pdf
file_size: 7076870
relation: main_file
success: 1
file_date_updated: 2020-12-10T14:01:10Z
has_accepted_license: '1'
intvolume: ' 212'
isi: 1
issue: '3'
keyword:
- electron microscopy
- cryo-EM
- EM sample preparation
- 3D printing
- cell culture
language:
- iso: eng
month: '12'
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
- _id: 059B463C-7A3F-11EA-A408-12923DDC885E
name: NÖ-Fonds Preis für die Jungforscherin des Jahres am IST Austria
publication: Journal of Structural Biology
publication_identifier:
issn:
- 1047-8477
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '14592'
relation: used_in_publication
status: public
- id: '12491'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: 3D printed cell culture grid holders for improved cellular specimen preparation
in cryo-electron microscopy
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: 212
year: '2020'
...
---
_id: '8657'
abstract:
- lang: eng
text: "Synthesis of proteins – translation – is a fundamental process of life. Quantitative
studies anchor translation into the context of bacterial physiology and reveal
several mathematical relationships, called “growth laws,” which capture physiological
feedbacks between protein synthesis and cell growth. Growth laws describe the
dependency of the ribosome abundance as a function of growth rate, which can change
depending on the growth conditions. Perturbations of translation reveal that bacteria
employ a compensatory strategy in which the reduced translation capability results
in increased expression of the translation machinery.\r\nPerturbations of translation
are achieved in various ways; clinically interesting is the application of translation-targeting
antibiotics – translation inhibitors. The antibiotic effects on bacterial physiology
are often poorly understood. Bacterial responses to two or more simultaneously
applied antibiotics are even more puzzling. The combined antibiotic effect determines
the type of drug interaction, which ranges from synergy (the effect is stronger
than expected) to antagonism (the effect is weaker) and suppression (one of the
drugs loses its potency).\r\nIn the first part of this work, we systematically
measure the pairwise interaction network for translation inhibitors that interfere
with different steps in translation. We find that the interactions are surprisingly
diverse and tend to be more antagonistic. To explore the underlying mechanisms,
we begin with a minimal biophysical model of combined antibiotic action. We base
this model on the kinetics of antibiotic uptake and binding together with the
physiological response described by the growth laws. The biophysical model explains
some drug interactions, but not all; it specifically fails to predict suppression.\r\nIn
the second part of this work, we hypothesize that elusive suppressive drug interactions
result from the interplay between ribosomes halted in different stages of translation.
To elucidate this putative mechanism of drug interactions between translation
inhibitors, we generate translation bottlenecks genetically using in- ducible
control of translation factors that regulate well-defined translation cycle steps.
These perturbations accurately mimic antibiotic action and drug interactions,
supporting that the interplay of different translation bottlenecks partially causes
these interactions.\r\nWe extend this approach by varying two translation bottlenecks
simultaneously. This approach reveals the suppression of translocation inhibition
by inhibited translation. We rationalize this effect by modeling dense traffic
of ribosomes that move on transcripts in a translation factor-mediated manner.
This model predicts a dissolution of traffic jams caused by inhibited translocation
when the density of ribosome traffic is reduced by lowered initiation. We base
this model on the growth laws and quantitative relationships between different
translation and growth parameters.\r\nIn the final part of this work, we describe
a set of tools aimed at quantification of physiological and translation parameters.
We further develop a simple model that directly connects the abundance of a translation
factor with the growth rate, which allows us to extract physiological parameters
describing initiation. We demonstrate the development of tools for measuring translation
rate.\r\nThis thesis showcases how a combination of high-throughput growth rate
mea- surements, genetics, and modeling can reveal mechanisms of drug interactions.
Furthermore, by a gradual transition from combinations of antibiotics to precise
genetic interventions, we demonstrated the equivalency between genetic and chemi-
cal perturbations of translation. These findings tile the path for quantitative
studies of antibiotic combinations and illustrate future approaches towards the
quantitative description of translation."
acknowledged_ssus:
- _id: LifeSc
- _id: M-Shop
acknowledgement: I thank Life Science Facilities for their continuous support with
providing top-notch laboratory materials, keeping the devices humming, and coordinating
the repairs and building of custom-designed laboratory equipment with the MIBA Machine
shop.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
citation:
ama: 'Kavcic B. Perturbations of protein synthesis: from antibiotics to genetics
and physiology. 2020. doi:10.15479/AT:ISTA:8657'
apa: 'Kavcic, B. (2020). Perturbations of protein synthesis: from antibiotics
to genetics and physiology. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8657'
chicago: 'Kavcic, Bor. “Perturbations of Protein Synthesis: From Antibiotics to
Genetics and Physiology.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8657.'
ieee: 'B. Kavcic, “Perturbations of protein synthesis: from antibiotics to genetics
and physiology,” Institute of Science and Technology Austria, 2020.'
ista: 'Kavcic B. 2020. Perturbations of protein synthesis: from antibiotics to genetics
and physiology. Institute of Science and Technology Austria.'
mla: 'Kavcic, Bor. Perturbations of Protein Synthesis: From Antibiotics to Genetics
and Physiology. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8657.'
short: 'B. Kavcic, Perturbations of Protein Synthesis: From Antibiotics to Genetics
and Physiology, Institute of Science and Technology Austria, 2020.'
date_created: 2020-10-13T16:46:14Z
date_published: 2020-10-14T00:00:00Z
date_updated: 2023-09-07T13:20:48Z
day: '14'
ddc:
- '571'
- '530'
- '570'
degree_awarded: PhD
department:
- _id: GaTk
doi: 10.15479/AT:ISTA:8657
file:
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content_type: application/pdf
creator: bkavcic
date_created: 2020-10-15T06:41:20Z
date_updated: 2021-10-07T22:30:03Z
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has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '271'
publication_identifier:
isbn:
- 978-3-99078-011-4
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7673'
relation: part_of_dissertation
status: public
- id: '8250'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
title: 'Perturbations of protein synthesis: from antibiotics to genetics and physiology'
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...