---
_id: '10'
abstract:
- lang: eng
text: Genomic imprinting is an epigenetic process that leads to parent of origin-specific
gene expression in a subset of genes. Imprinted genes are essential for brain
development, and deregulation of imprinting is associated with neurodevelopmental
diseases and the pathogenesis of psychiatric disorders. However, the cell-type
specificity of imprinting at single cell resolution, and how imprinting and thus
gene dosage regulates neuronal circuit assembly is still largely unknown. Here,
MADM (Mosaic Analysis with Double Markers) technology was employed to assess genomic
imprinting at single cell level. By visualizing MADM-induced uniparental disomies
(UPDs) in distinct colors at single cell level in genetic mosaic animals, this
experimental paradigm provides a unique quantitative platform to systematically
assay the UPD-mediated imbalances in imprinted gene expression at unprecedented
resolution. An experimental pipeline based on FACS, RNA-seq and bioinformatics
analysis was established and applied to systematically map cell-type-specific
‘imprintomes’ in the mouse brain. The results revealed that parental-specific
expression of imprinted genes per se is rarely cell-type-specific even at the
individual cell level. Conversely, when we extended the comparison to downstream
responses resulting from imbalanced imprinted gene expression, we discovered an
unexpectedly high degree of cell-type specificity. Furthermore, we determined
a novel function of genomic imprinting in cortical astrocyte production and in
olfactory bulb (OB) granule cell generation. These results suggest important functional
implication of genomic imprinting for generating cell-type diversity in the brain.
In addition, MADM provides a powerful tool to study candidate genes by concomitant
genetic manipulation and fluorescent labelling of single cells. MADM-based candidate
gene approach was utilized to identify potential imprinted genes involved in the
generation of cortical astrocytes and OB granule cells. We investigated p57Kip2,
a maternally expressed gene and known cell cycle regulator. Although we found
that p57Kip2 does not play a role in these processes, we detected an unexpected
function of the paternal allele previously thought to be silent. Finally, we took
advantage of a key property of MADM which is to allow unambiguous investigation
of environmental impact on single cells. The experimental pipeline based on FACS
and RNA-seq analysis of MADM-labeled cells was established to probe the functional
differences of single cell loss of gene function compared to global loss of function
on a transcriptional level. With this method, both common and distinct responses
were isolated due to cell-autonomous and non-autonomous effects acting on genotypically
identical cells. As a result, transcriptional changes were identified which result
solely from the surrounding environment. Using the MADM technology to study genomic
imprinting at single cell resolution, we have identified cell-type-specific gene
expression, novel gene function and the impact of environment on single cell transcriptomes.
Together, these provide important insights to the understanding of mechanisms
regulating cell-type specificity and thus diversity in the brain.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
citation:
ama: Laukoter S. Role of genomic imprinting in cerebral cortex development. 2018:1-139.
doi:10.15479/AT:ISTA:th1057
apa: Laukoter, S. (2018). Role of genomic imprinting in cerebral cortex development.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th1057
chicago: Laukoter, Susanne. “Role of Genomic Imprinting in Cerebral Cortex Development.”
Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th1057.
ieee: S. Laukoter, “Role of genomic imprinting in cerebral cortex development,”
Institute of Science and Technology Austria, 2018.
ista: Laukoter S. 2018. Role of genomic imprinting in cerebral cortex development.
Institute of Science and Technology Austria.
mla: Laukoter, Susanne. Role of Genomic Imprinting in Cerebral Cortex Development.
Institute of Science and Technology Austria, 2018, pp. 1–139, doi:10.15479/AT:ISTA:th1057.
short: S. Laukoter, Role of Genomic Imprinting in Cerebral Cortex Development, Institute
of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:44:08Z
date_published: 2018-11-21T00:00:00Z
date_updated: 2023-09-07T12:40:44Z
day: '21'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: SiHi
doi: 10.15479/AT:ISTA:th1057
file:
- access_level: closed
checksum: 41fdbf5fdce312802935d88a8ad9932c
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: dernst
date_created: 2019-05-10T07:47:04Z
date_updated: 2019-11-23T23:30:03Z
embargo_to: open_access
file_id: '6396'
file_name: Thesis_LaukoterSusanne_FINAL.docx
file_size: 17949175
relation: source_file
- access_level: open_access
checksum: 53001a9a0c9e570e598d861bb0af28aa
content_type: application/pdf
creator: dernst
date_created: 2019-05-10T07:47:04Z
date_updated: 2021-02-11T11:17:16Z
embargo: 2019-11-21
file_id: '6397'
file_name: Thesis_LaukoterSusanne_FINAL.pdf
file_size: 21187245
relation: main_file
file_date_updated: 2021-02-11T11:17:16Z
has_accepted_license: '1'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: 1 - 139
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '8046'
pubrep_id: '1057'
status: public
supervisor:
- first_name: Beatriz
full_name: Vicoso, Beatriz
id: 49E1C5C6-F248-11E8-B48F-1D18A9856A87
last_name: Vicoso
orcid: 0000-0002-4579-8306
title: Role of genomic imprinting in cerebral cortex development
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...
---
_id: '323'
abstract:
- lang: eng
text: 'In the here presented thesis, we explore the role of branched actin networks
in cell migration and antigen presentation, the two most relevant processes in
dendritic cell biology. Branched actin networks construct lamellipodial protrusions
at the leading edge of migrating cells. These are typically seen as adhesive structures,
which mediate force transduction to the extracellular matrix that leads to forward
locomotion. We ablated Arp2/3 nucleation promoting factor WAVE in DCs and found
that the resulting cells lack lamellipodial protrusions. Instead, depending on
the maturation state, one or multiple filopodia were formed. By challenging these
cells in a variety of migration assays we found that lamellipodial protrusions
are dispensable for the locomotion of leukocytes and actually dampen the speed
of migration. However, lamellipodia are critically required to negotiate complex
environments that DCs experience while they travel to the next draining lymph
node. Taken together our results suggest that leukocyte lamellipodia have rather
a sensory- than a force transducing function. Furthermore, we show for the first
time structure and dynamics of dendritic cell F-actin at the immunological synapse
with naïve T cells. Dendritic cell F-actin appears as dynamic foci that are nucleated
by the Arp2/3 complex. WAVE ablated dendritic cells show increased membrane tension,
leading to an altered ultrastructure of the immunological synapse and severe T
cell priming defects. These results point towards a previously unappreciated role
of the cellular mechanics of dendritic cells in T cell activation. Additionally,
we present a novel cell culture based system for the differentiation of dendritic
cells from conditionally immortalized hematopoietic precursors. These precursor
cells are genetically tractable via the CRISPR/Cas9 system while they retain their
ability to differentiate into highly migratory dendritic cells and other immune
cells. This will foster the study of all aspects of dendritic cell biology and
beyond. '
acknowledged_ssus:
- _id: NanoFab
- _id: Bio
- _id: PreCl
- _id: EM-Fac
acknowledgement: "First of all I would like to thank Michael Sixt for giving me the
opportunity to work in \r\nhis group and for his support throughout the years. He
is a truly inspiring person and \r\nthe best boss one can imagine. I would
\ also like to thank all current and past \r\nmembers of the Sixt group for
their help and the great working atmosphere in the lab. \r\nIt is a true privilege
to work with such a bright, funny and friendly group of people and \r\nI’m proud
\ that I could be part of it. Furthermore, I would like to say ‘thank
\ you’ to Daria Siekhaus for all the meetings and discussion we had throughout
the years \r\nand to Federica Benvenuti for being part of my committee.
\ I am also grateful to Jack \r\nMerrin in the nanofabrication facility
\ and all the people working in the bioimaging-\r\n, the electron microscopy-
and the preclinical facilities."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
citation:
ama: Leithner AF. Branched actin networks in dendritic cell biology. 2018. doi:10.15479/AT:ISTA:th_998
apa: Leithner, A. F. (2018). Branched actin networks in dendritic cell biology.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_998
chicago: Leithner, Alexander F. “Branched Actin Networks in Dendritic Cell Biology.”
Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_998.
ieee: A. F. Leithner, “Branched actin networks in dendritic cell biology,” Institute
of Science and Technology Austria, 2018.
ista: Leithner AF. 2018. Branched actin networks in dendritic cell biology. Institute
of Science and Technology Austria.
mla: Leithner, Alexander F. Branched Actin Networks in Dendritic Cell Biology.
Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_998.
short: A.F. Leithner, Branched Actin Networks in Dendritic Cell Biology, Institute
of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:45:49Z
date_published: 2018-04-12T00:00:00Z
date_updated: 2023-09-07T12:39:44Z
day: '12'
ddc:
- '571'
- '599'
- '610'
degree_awarded: PhD
department:
- _id: MiSi
doi: 10.15479/AT:ISTA:th_998
file:
- access_level: closed
checksum: d5e3edbac548c26c1fa43a4b37a54a4c
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: dernst
date_created: 2019-04-05T09:23:11Z
date_updated: 2021-02-11T23:30:17Z
embargo_to: open_access
file_id: '6219'
file_name: PhD_thesis_AlexLeithner_final_version.docx
file_size: 29027671
relation: source_file
- access_level: open_access
checksum: 071f7476db29e41146824ebd0697cb10
content_type: application/pdf
creator: dernst
date_created: 2019-04-05T09:23:11Z
date_updated: 2021-02-11T11:17:16Z
embargo: 2019-04-15
file_id: '6220'
file_name: PhD_thesis_AlexLeithner.pdf
file_size: 66045341
relation: main_file
file_date_updated: 2021-02-11T23:30:17Z
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: '99'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '7542'
pubrep_id: '998'
related_material:
record:
- id: '1321'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
title: Branched actin networks in dendritic cell biology
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...
---
_id: '539'
abstract:
- lang: eng
text: The whole life cycle of plants as well as their responses to environmental
stimuli is governed by a complex network of hormonal regulations. A number of
studies have demonstrated an essential role of both auxin and cytokinin in the
regulation of many aspects of plant growth and development including embryogenesis,
postembryonic organogenic processes such as root, and shoot branching, root and
shoot apical meristem activity and phyllotaxis. Over the last decades essential
knowledge on the key molecular factors and pathways that spatio-temporally define
auxin and cytokinin activities in the plant body has accumulated. However, how
both hormonal pathways are interconnected by a complex network of interactions
and feedback circuits that determines the final outcome of the individual hormone
actions is still largely unknown. Root system architecture establishment and in
particular formation of lateral organs is prime example of developmental process
at whose regulation both auxin and cytokinin pathways converge. To dissect convergence
points and pathways that tightly balance auxin - cytokinin antagonistic activities
that determine the root branching pattern transcriptome profiling was applied.
Genome wide expression analyses of the xylem pole pericycle, a tissue giving rise
to lateral roots, led to identification of genes that are highly responsive to
combinatorial auxin and cytokinin treatments and play an essential function in
the auxin-cytokinin regulated root branching. SYNERGISTIC AUXIN CYTOKININ 1 (SYAC1)
gene, which encodes for a protein of unknown function, was detected among the
top candidate genes of which expression was synergistically up-regulated by simultaneous
hormonal treatment. Plants with modulated SYAC1 activity exhibit severe defects
in the root system establishment and attenuate developmental responses to both
auxin and cytokinin. To explore the biological function of the SYAC1, we employed
different strategies including expression pattern analysis, subcellular localization
and phenotypic analyses of the syac1 loss-of-function and gain-of-function transgenic
lines along with the identification of the SYAC1 interaction partners. Detailed
functional characterization revealed that SYAC1 acts as a developmentally specific
regulator of the secretory pathway to control deposition of cell wall components
and thereby rapidly fine tune elongation growth.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Andrej
full_name: Hurny, Andrej
id: 4DC4AF46-F248-11E8-B48F-1D18A9856A87
last_name: Hurny
orcid: 0000-0003-3638-1426
citation:
ama: Hurny A. Identification and characterization of novel auxin-cytokinin cross-talk
components. 2018. doi:10.15479/AT:ISTA:th_930
apa: Hurny, A. (2018). Identification and characterization of novel auxin-cytokinin
cross-talk components. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_930
chicago: Hurny, Andrej. “Identification and Characterization of Novel Auxin-Cytokinin
Cross-Talk Components.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_930.
ieee: A. Hurny, “Identification and characterization of novel auxin-cytokinin cross-talk
components,” Institute of Science and Technology Austria, 2018.
ista: Hurny A. 2018. Identification and characterization of novel auxin-cytokinin
cross-talk components. Institute of Science and Technology Austria.
mla: Hurny, Andrej. Identification and Characterization of Novel Auxin-Cytokinin
Cross-Talk Components. Institute of Science and Technology Austria, 2018,
doi:10.15479/AT:ISTA:th_930.
short: A. Hurny, Identification and Characterization of Novel Auxin-Cytokinin Cross-Talk
Components, Institute of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:47:03Z
date_published: 2018-01-01T00:00:00Z
date_updated: 2023-09-07T12:41:06Z
day: '01'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: EvBe
doi: 10.15479/AT:ISTA:th_930
file:
- access_level: closed
checksum: 0c9d6d1c80d9857e6e545213467bbcb2
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: dernst
date_created: 2019-04-05T09:37:56Z
date_updated: 2020-12-02T23:30:08Z
embargo_to: open_access
file_id: '6226'
file_name: 2018_Hurny_thesis_source.docx
file_size: 28112114
relation: source_file
- access_level: open_access
checksum: ecbe481a1413d270bd501b872c7ed54f
content_type: application/pdf
creator: dernst
date_created: 2019-04-05T09:37:55Z
date_updated: 2020-12-02T09:52:16Z
embargo: 2019-07-10
file_id: '6227'
file_name: 2018_Hurny_thesis.pdf
file_size: 12524427
relation: main_file
file_date_updated: 2020-12-02T23:30:08Z
has_accepted_license: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: '147'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '7277'
pubrep_id: '930'
related_material:
record:
- id: '1024'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Eva
full_name: Benková, Eva
id: 38F4F166-F248-11E8-B48F-1D18A9856A87
last_name: Benková
orcid: 0000-0002-8510-9739
title: Identification and characterization of novel auxin-cytokinin cross-talk components
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...
---
_id: '48'
abstract:
- lang: eng
text: 'The hippocampus is a key brain region for spatial memory and navigation and
is needed at all stages of memory, including encoding, consolidation, and recall.
Hippocampal place cells selectively discharge at specific locations of the environment
to form a cognitive map of the space. During the rest period and sleep following
spatial navigation and/or learning, the waking activity of the place cells is
reactivated within high synchrony events. This reactivation is thought to be important
for memory consolidation and stabilization of the spatial representations. The
aim of my thesis was to directly test whether the reactivation content encoded
in firing patterns of place cells is important for consolidation of spatial memories.
In particular, I aimed to test whether, in cases when multiple spatial memory
traces are acquired during learning, the specific disruption of the reactivation
of a subset of these memories leads to the selective disruption of the corresponding
memory traces or through memory interference the other learned memories are disrupted
as well. In this thesis, using a modified cheeseboard paradigm and a closed-loop
recording setup with feedback optogenetic stimulation, I examined how the disruption
of the reactivation of specific spiking patterns affects consolidation of the
corresponding memory traces. To obtain multiple distinctive memories, animals
had to perform a spatial task in two distinct cheeseboard environments and the
reactivation of spiking patterns associated with one of the environments (target)
was disrupted after learning during four hours rest period using a real-time decoding
method. This real-time decoding method was capable of selectively affecting the
firing rates and cofiring correlations of the target environment-encoding cells.
The selective disruption led to behavioural impairment in the memory tests after
the rest periods in the target environment but not in the other undisrupted control
environment. In addition, the map of the target environment was less stable in
the impaired memory tests compared to the learning session before than the map
of the control environment. However, when the animal relearned the task, the same
map recurred in the target environment that was present during learning before
the disruption. Altogether my work demonstrated that the reactivation content
is important: assembly-related disruption of reactivation can lead to a selective
memory impairment and deficiency in map stability. These findings indeed suggest
that reactivated assembly patterns reflect processes associated with the consolidation
of memory traces. '
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Igor
full_name: Gridchyn, Igor
id: 4B60654C-F248-11E8-B48F-1D18A9856A87
last_name: Gridchyn
orcid: 0000-0002-1807-1929
citation:
ama: Gridchyn I. Reactivation content is important for consolidation of spatial
memory. 2018. doi:10.15479/AT:ISTA:th_1042
apa: Gridchyn, I. (2018). Reactivation content is important for consolidation
of spatial memory. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_1042
chicago: Gridchyn, Igor. “Reactivation Content Is Important for Consolidation of
Spatial Memory.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_1042.
ieee: I. Gridchyn, “Reactivation content is important for consolidation of spatial
memory,” Institute of Science and Technology Austria, 2018.
ista: Gridchyn I. 2018. Reactivation content is important for consolidation of spatial
memory. Institute of Science and Technology Austria.
mla: Gridchyn, Igor. Reactivation Content Is Important for Consolidation of Spatial
Memory. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_1042.
short: I. Gridchyn, Reactivation Content Is Important for Consolidation of Spatial
Memory, Institute of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:44:21Z
date_published: 2018-08-27T00:00:00Z
date_updated: 2023-09-07T12:42:44Z
day: '27'
ddc:
- '573'
degree_awarded: PhD
department:
- _id: JoCs
doi: 10.15479/AT:ISTA:th_1042
file:
- access_level: closed
checksum: 7db4415e435590fa33542c7b0a0321d7
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: dernst
date_created: 2019-04-08T13:36:01Z
date_updated: 2021-02-11T23:30:22Z
embargo_to: open_access
file_id: '6236'
file_name: 2018_Thesis_Gridchyn_source.docx
file_size: 7666687
relation: source_file
- access_level: open_access
checksum: f96f3fe8979f7b1e6db6acaca962b10c
content_type: application/pdf
creator: dernst
date_created: 2019-04-08T13:36:01Z
date_updated: 2021-02-11T11:17:18Z
embargo: 2019-08-29
file_id: '6237'
file_name: 2018_Thesis_Gridchyn.pdf
file_size: 6034153
relation: main_file
file_date_updated: 2021-02-11T23:30:22Z
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '104'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '8006'
pubrep_id: '1042'
status: public
supervisor:
- first_name: Jozsef L
full_name: Csicsvari, Jozsef L
id: 3FA14672-F248-11E8-B48F-1D18A9856A87
last_name: Csicsvari
orcid: 0000-0002-5193-4036
title: Reactivation content is important for consolidation of spatial memory
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...
---
_id: '9'
abstract:
- lang: eng
text: 'Immune cells migrating to the sites of infection navigate through diverse
tissue architectures and switch their migratory mechanisms upon demand. However,
little is known about systemic regulators that could allow the acquisition of
these mechanisms. We performed a genetic screen in Drosophila melanogaster to
identify regulators of germband invasion by embryonic macrophages into the confined
space between the ectoderm and mesoderm. We have found that bZIP circadian transcription
factors (TFs) Kayak (dFos) and Vrille (dNFIL3) have opposite effects on macrophage
germband infiltration: Kayak facilitated and Vrille inhibited it. These TFs are
enriched in the macrophages during migration and genetically interact to control
it. Kayak sets a less coordinated mode of migration of the macrophage group and
increases the probability and length of Levy walks. Intriguingly, the motility
of kayak mutant macrophages was also strongly affected during initial germband
invasion but not along another less confined route. Inhibiting Rho1 signaling
within the tail ectoderm partially rescued the Kayak mutant phenotype, strongly
suggesting that migrating macrophages have to overcome a barrier imposed by the
stiffness of the ectoderm. Also, Kayak appeared to be important for the maintenance
of the round cell shape and the rear edge translocation of the macrophages invading
the germband. Complementary to this, the cortical actin cytoskeleton of Kayak-
deficient macrophages was strongly affected. RNA sequencing revealed the filamin
Cheerio and tetraspanin TM4SF to be downstream of Kayak. Chromatin immunoprecipitation
and immunostaining revealed that the formin Diaphanous is another downstream target
of Kayak. Immunostaining revealed that the formin Diaphanous is another downstream
target of Kayak. Indeed, Cheerio, TM4SF and Diaphanous are required within macrophages
for germband invasion, and expression of constitutively active Diaphanous in macrophages
was able to rescue the kayak mutant phenotype. Moreover, Cher and Diaphanous are
also reduced in the macrophages overexpressing Vrille. We hypothesize that Kayak,
through its targets, increases actin polymerization and cortical tension in macrophages
and thus allows extra force generation necessary for macrophage dissemination
and migration through confined stiff tissues, while Vrille counterbalances it.'
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Vera
full_name: Belyaeva, Vera
id: 47F080FE-F248-11E8-B48F-1D18A9856A87
last_name: Belyaeva
citation:
ama: Belyaeva V. Transcriptional regulation of macrophage migration in the Drosophila
melanogaster embryo . 2018. doi:10.15479/AT:ISTA:th1064
apa: Belyaeva, V. (2018). Transcriptional regulation of macrophage migration
in the Drosophila melanogaster embryo . Institute of Science and Technology
Austria. https://doi.org/10.15479/AT:ISTA:th1064
chicago: Belyaeva, Vera. “Transcriptional Regulation of Macrophage Migration in
the Drosophila Melanogaster Embryo .” Institute of Science and Technology Austria,
2018. https://doi.org/10.15479/AT:ISTA:th1064.
ieee: V. Belyaeva, “Transcriptional regulation of macrophage migration in the Drosophila
melanogaster embryo ,” Institute of Science and Technology Austria, 2018.
ista: Belyaeva V. 2018. Transcriptional regulation of macrophage migration in the
Drosophila melanogaster embryo . Institute of Science and Technology Austria.
mla: Belyaeva, Vera. Transcriptional Regulation of Macrophage Migration in the
Drosophila Melanogaster Embryo . Institute of Science and Technology Austria,
2018, doi:10.15479/AT:ISTA:th1064.
short: V. Belyaeva, Transcriptional Regulation of Macrophage Migration in the Drosophila
Melanogaster Embryo , Institute of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:44:08Z
date_published: 2018-07-01T00:00:00Z
date_updated: 2023-09-07T12:43:10Z
day: '01'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: DaSi
doi: 10.15479/AT:ISTA:th1064
file:
- access_level: closed
checksum: d27b2465cb70d0c9678a0381b9b6ced1
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: dernst
date_created: 2019-04-08T14:13:12Z
date_updated: 2020-07-14T12:48:14Z
embargo_to: open_access
file_id: '6243'
file_name: 2018_Thesis_Belyaeva_source.docx
file_size: 102737483
relation: source_file
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checksum: a2939b61bde2de7b8ced77bbae0eaaed
content_type: application/pdf
creator: dernst
date_created: 2019-04-08T14:14:08Z
date_updated: 2021-02-11T11:17:16Z
embargo: 2019-11-19
file_id: '6244'
file_name: 2018_Thesis_Belyaeva.pdf
file_size: 88077843
relation: main_file
file_date_updated: 2021-02-11T11:17:16Z
has_accepted_license: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: '96'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '8047'
pubrep_id: '1064'
status: public
supervisor:
- first_name: Daria E
full_name: Siekhaus, Daria E
id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
last_name: Siekhaus
orcid: 0000-0001-8323-8353
title: 'Transcriptional regulation of macrophage migration in the Drosophila melanogaster
embryo '
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...
---
_id: '6266'
abstract:
- lang: eng
text: 'A major challenge in neuroscience research is to dissect the circuits that
orchestrate behavior in health and disease. Proteins from a wide range of non-mammalian
species, such as microbial opsins, have been successfully transplanted to specific
neuronal targets to override their natural communication patterns. The goal of
our work is to manipulate synaptic communication in a manner that closely incorporates
the functional intricacies of synapses by preserving temporal encoding (i.e. the
firing pattern of the presynaptic neuron) and connectivity (i.e. target specific
synapses rather than specific neurons). Our strategy to achieve this goal builds
on the use of non-mammalian transplants to create a synthetic synapse. The mode
of modulation comes from pre-synaptic uptake of a synthetic neurotransmitter (SN)
into synaptic vesicles by means of a genetically targeted transporter selective
for the SN. Upon natural vesicular release, exposure of the SN to the synaptic
cleft will modify the post-synaptic potential through an orthogonal ligand gated
ion channel. To achieve this goal we have functionally characterized a mixed cationic
methionine-gated ion channel from Arabidopsis thaliana, designed a method to functionally
characterize a synthetic transporter in isolated synaptic vesicles without the
need for transgenic animals, identified and extracted multiple prokaryotic uptake
systems that are substrate specific for methionine (Met), and established a primary/cell
line co-culture system that would allow future combinatorial testing of this orthogonal
transmitter-transporter-channel trifecta. Synthetic synapses will provide a unique
opportunity to manipulate synaptic communication while maintaining the electrophysiological
integrity of the pre-synaptic cell. In this way, information may be preserved
that was generated in upstream circuits and that could be essential for concerted
function and information processing. '
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Catherine
full_name: Mckenzie, Catherine
id: 3EEDE19A-F248-11E8-B48F-1D18A9856A87
last_name: Mckenzie
citation:
ama: Mckenzie C. Design and characterization of methods and biological components
to realize synthetic neurotransmission . 2018. doi:10.15479/at:ista:th_1055
apa: Mckenzie, C. (2018). Design and characterization of methods and biological
components to realize synthetic neurotransmission . Institute of Science and
Technology Austria. https://doi.org/10.15479/at:ista:th_1055
chicago: Mckenzie, Catherine. “Design and Characterization of Methods and Biological
Components to Realize Synthetic Neurotransmission .” Institute of Science and
Technology Austria, 2018. https://doi.org/10.15479/at:ista:th_1055.
ieee: C. Mckenzie, “Design and characterization of methods and biological components
to realize synthetic neurotransmission ,” Institute of Science and Technology
Austria, 2018.
ista: Mckenzie C. 2018. Design and characterization of methods and biological components
to realize synthetic neurotransmission . Institute of Science and Technology Austria.
mla: Mckenzie, Catherine. Design and Characterization of Methods and Biological
Components to Realize Synthetic Neurotransmission . Institute of Science and
Technology Austria, 2018, doi:10.15479/at:ista:th_1055.
short: C. Mckenzie, Design and Characterization of Methods and Biological Components
to Realize Synthetic Neurotransmission , Institute of Science and Technology Austria,
2018.
date_created: 2019-04-09T14:13:39Z
date_published: 2018-10-31T00:00:00Z
date_updated: 2023-09-07T13:02:37Z
day: '31'
ddc:
- '571'
- '573'
degree_awarded: PhD
department:
- _id: HaJa
doi: 10.15479/at:ista:th_1055
file:
- access_level: open_access
checksum: 9d2c2dca04b00e485470c28b262af59a
content_type: application/pdf
creator: dernst
date_created: 2019-04-09T14:12:40Z
date_updated: 2021-02-11T11:17:16Z
embargo: 2019-11-24
file_id: '6267'
file_name: 2018_Thesis_McKenzie.pdf
file_size: 4906420
relation: main_file
- access_level: closed
checksum: 50b58c272899601bc6fd9642c4dc97f1
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: dernst
date_created: 2019-04-09T14:12:40Z
date_updated: 2020-07-14T12:47:25Z
embargo_to: open_access
file_id: '6268'
file_name: 2018_Thesis_McKenzie_source.docx
file_size: 5053545
relation: source_file
file_date_updated: 2021-02-11T11:17:16Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '95'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
pubrep_id: '1055'
related_material:
record:
- id: '7132'
relation: new_edition
status: public
status: public
supervisor:
- first_name: Harald L
full_name: Janovjak, Harald L
id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
last_name: Janovjak
orcid: 0000-0002-8023-9315
title: 'Design and characterization of methods and biological components to realize
synthetic neurotransmission '
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...
---
_id: '50'
abstract:
- lang: eng
text: The Wnt/planar cell polarity (Wnt/PCP) pathway determines planar polarity
of epithelial cells in both vertebrates and invertebrates. The role that Wnt/PCP
signaling plays in mesenchymal contexts, however, is only poorly understood. While
previous studies have demonstrated the capacity of Wnt/PCP signaling to polarize
and guide directed migration of mesenchymal cells, it remains unclear whether
endogenous Wnt/PCP signaling performs these functions instructively, as it does
in epithelial cells. Here we developed a light-switchable version of the Wnt/PCP
receptor Frizzled 7 (Fz7) to unambiguously distinguish between an instructive
and a permissive role of Wnt/PCP signaling for the directional collective migration
of mesendoderm progenitor cells during zebrafish gastrulation. We show that prechordal
plate (ppl) cell migration is defective in maternal-zygotic fz7a and fz7b (MZ
fz7a,b) double mutant embryos, and that Fz7 functions cell-autonomously in this
process by promoting ppl cell protrusion formation and directed migration. We
further show that local activation of Fz7 can direct ppl cell migration both in
vitro and in vivo. Surprisingly, however, uniform Fz7 activation is sufficient
to fully rescue the ppl cell migration defect in MZ fz7a,b mutant embryos, indicating
that Wnt/PCP signaling functions permissively rather than instructively in directed
mesendoderm cell migration during zebrafish gastrulation.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Daniel
full_name: Capek, Daniel
id: 31C42484-F248-11E8-B48F-1D18A9856A87
last_name: Capek
orcid: 0000-0001-5199-9940
citation:
ama: Capek D. Optogenetic Frizzled 7 reveals a permissive function of Wnt/PCP signaling
in directed mesenchymal cell migration. 2018. doi:10.15479/AT:ISTA:TH_1031
apa: Capek, D. (2018). Optogenetic Frizzled 7 reveals a permissive function of
Wnt/PCP signaling in directed mesenchymal cell migration. Institute of Science
and Technology Austria. https://doi.org/10.15479/AT:ISTA:TH_1031
chicago: Capek, Daniel. “Optogenetic Frizzled 7 Reveals a Permissive Function of
Wnt/PCP Signaling in Directed Mesenchymal Cell Migration.” Institute of Science
and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:TH_1031.
ieee: D. Capek, “Optogenetic Frizzled 7 reveals a permissive function of Wnt/PCP
signaling in directed mesenchymal cell migration,” Institute of Science and Technology
Austria, 2018.
ista: Capek D. 2018. Optogenetic Frizzled 7 reveals a permissive function of Wnt/PCP
signaling in directed mesenchymal cell migration. Institute of Science and Technology
Austria.
mla: Capek, Daniel. Optogenetic Frizzled 7 Reveals a Permissive Function of Wnt/PCP
Signaling in Directed Mesenchymal Cell Migration. Institute of Science and
Technology Austria, 2018, doi:10.15479/AT:ISTA:TH_1031.
short: D. Capek, Optogenetic Frizzled 7 Reveals a Permissive Function of Wnt/PCP
Signaling in Directed Mesenchymal Cell Migration, Institute of Science and Technology
Austria, 2018.
date_created: 2018-12-11T11:44:21Z
date_published: 2018-06-22T00:00:00Z
date_updated: 2023-09-07T12:48:16Z
day: '22'
ddc:
- '570'
- '591'
- '596'
degree_awarded: PhD
department:
- _id: CaHe
doi: 10.15479/AT:ISTA:TH_1031
file:
- access_level: open_access
checksum: d3eca3dcacb67bffdde6e6609c31cdd0
content_type: application/pdf
creator: dernst
date_created: 2019-04-08T13:42:26Z
date_updated: 2021-02-11T11:17:17Z
embargo: 2019-06-25
file_id: '6238'
file_name: 2018_Thesis_Capek.pdf
file_size: 31576521
relation: main_file
- access_level: closed
checksum: 876deb14067e638aba65d209668bd821
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: dernst
date_created: 2019-04-08T13:42:27Z
date_updated: 2021-02-11T23:30:21Z
embargo_to: open_access
file_id: '6239'
file_name: 2018_Thesis_Capek_source.docx
file_size: 38992956
relation: source_file
file_date_updated: 2021-02-11T23:30:21Z
has_accepted_license: '1'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: '95'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '8004'
pubrep_id: '1031'
related_material:
record:
- id: '1100'
relation: part_of_dissertation
status: public
- id: '661'
relation: part_of_dissertation
status: public
- id: '676'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
title: Optogenetic Frizzled 7 reveals a permissive function of Wnt/PCP signaling in
directed mesenchymal cell migration
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...
---
_id: '26'
abstract:
- lang: eng
text: Expression of genes is a fundamental molecular phenotype that is subject to
evolution by different types of mutations. Both the rate and the effect of mutations
may depend on the DNA sequence context of a particular gene or a particular promoter
sequence. In this thesis I investigate the nature of this dependence using simple
genetic systems in Escherichia coli. With these systems I explore the evolution
of constitutive gene expression from random starting sequences at different loci
on the chromosome and at different locations in sequence space. First, I dissect
chromosomal neighborhood effects that underlie locus-dependent differences in
the potential of a gene under selection to become more highly expressed. Next,
I find that the effects of point mutations in promoter sequences are dependent
on sequence context, and that an existing energy matrix model performs poorly
in predicting relative expression of unrelated sequences. Finally, I show that
a substantial fraction of random sequences contain functional promoters and I
present an extended thermodynamic model that predicts promoter strength in full
sequence space. Taken together, these results provide new insights and guides
on how to integrate information on sequence context to improve our qualitative
and quantitative understanding of bacterial gene expression, with implications
for rapid evolution of drug resistance, de novo evolution of genes, and horizontal
gene transfer.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Magdalena
full_name: Steinrück, Magdalena
id: 2C023F40-F248-11E8-B48F-1D18A9856A87
last_name: Steinrück
orcid: 0000-0003-1229-9719
citation:
ama: Steinrück M. The influence of sequence context on the evolution of bacterial
gene expression. 2018. doi:10.15479/AT:ISTA:th1059
apa: Steinrück, M. (2018). The influence of sequence context on the evolution
of bacterial gene expression. Institute of Science and Technology Austria.
https://doi.org/10.15479/AT:ISTA:th1059
chicago: Steinrück, Magdalena. “The Influence of Sequence Context on the Evolution
of Bacterial Gene Expression.” Institute of Science and Technology Austria, 2018.
https://doi.org/10.15479/AT:ISTA:th1059.
ieee: M. Steinrück, “The influence of sequence context on the evolution of bacterial
gene expression,” Institute of Science and Technology Austria, 2018.
ista: Steinrück M. 2018. The influence of sequence context on the evolution of bacterial
gene expression. Institute of Science and Technology Austria.
mla: Steinrück, Magdalena. The Influence of Sequence Context on the Evolution
of Bacterial Gene Expression. Institute of Science and Technology Austria,
2018, doi:10.15479/AT:ISTA:th1059.
short: M. Steinrück, The Influence of Sequence Context on the Evolution of Bacterial
Gene Expression, Institute of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:44:14Z
date_published: 2018-10-30T00:00:00Z
date_updated: 2023-09-07T12:48:43Z
day: '30'
ddc:
- '576'
- '579'
degree_awarded: PhD
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:th1059
file:
- access_level: closed
checksum: 413cbce1cd1debeae3abe2a25dbc70d1
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: dernst
date_created: 2019-02-08T10:51:22Z
date_updated: 2020-07-14T12:45:43Z
embargo_to: open_access
file_id: '5941'
file_name: Thesis_Steinrueck_final.docx
file_size: 9190845
relation: source_file
- access_level: open_access
checksum: 3def8b7854c8b42d643597ce0215efac
content_type: application/pdf
creator: dernst
date_created: 2019-02-08T10:51:22Z
date_updated: 2021-02-11T11:17:14Z
embargo: 2019-11-02
file_id: '5942'
file_name: Thesis_Steinrueck_final.pdf
file_size: 7521973
relation: main_file
file_date_updated: 2021-02-11T11:17:14Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '109'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '8029'
pubrep_id: '1059'
related_material:
record:
- id: '704'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
title: The influence of sequence context on the evolution of bacterial gene expression
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...
---
_id: '5816'
abstract:
- lang: eng
text: Solid-state qubit manipulation and read-out fidelities are reaching fault-tolerance,
but quantum error correction requires millions of physical qubits and therefore
a scalable quantum computer architecture. To solve signal-line bandwidth and fan-out
problems, microwave sources required for qubit manipulation might be embedded
close to the qubit chip, typically operating at temperatures below 4 K. Here,
we perform the first low temperature measurements of a 130 nm BiCMOS based SiGe
voltage controlled oscillator at cryogenic temperature. We determined the frequency
and output power dependence on temperature and magnetic field up to 5 T and measured
the temperature influence on its noise performance. The device maintains its full
functionality from 300 K to 4 K. The carrier frequency at 4 K increases by 3%
with respect to the carrier frequency at 300 K, and the output power at 4 K increases
by 10 dB relative to the output power at 300 K. The frequency tuning range of
approximately 20% remains unchanged between 300 K and 4 K. In an in-plane magnetic
field of 5 T, the carrier frequency shifts by only 0.02% compared to the frequency
at zero magnetic field.
article_number: '114701'
article_processing_charge: No
author:
- first_name: Arne
full_name: Hollmann, Arne
last_name: Hollmann
- first_name: Daniel
full_name: Jirovec, Daniel
id: 4C473F58-F248-11E8-B48F-1D18A9856A87
last_name: Jirovec
orcid: 0000-0002-7197-4801
- first_name: Maciej
full_name: Kucharski, Maciej
last_name: Kucharski
- first_name: Dietmar
full_name: Kissinger, Dietmar
last_name: Kissinger
- first_name: Gunter
full_name: Fischer, Gunter
last_name: Fischer
- first_name: Lars R.
full_name: Schreiber, Lars R.
last_name: Schreiber
citation:
ama: Hollmann A, Jirovec D, Kucharski M, Kissinger D, Fischer G, Schreiber LR. 30
GHz-voltage controlled oscillator operating at 4 K. Review of Scientific Instruments.
2018;89(11). doi:10.1063/1.5038258
apa: Hollmann, A., Jirovec, D., Kucharski, M., Kissinger, D., Fischer, G., &
Schreiber, L. R. (2018). 30 GHz-voltage controlled oscillator operating at 4 K.
Review of Scientific Instruments. AIP Publishing. https://doi.org/10.1063/1.5038258
chicago: Hollmann, Arne, Daniel Jirovec, Maciej Kucharski, Dietmar Kissinger, Gunter
Fischer, and Lars R. Schreiber. “30 GHz-Voltage Controlled Oscillator Operating
at 4 K.” Review of Scientific Instruments. AIP Publishing, 2018. https://doi.org/10.1063/1.5038258.
ieee: A. Hollmann, D. Jirovec, M. Kucharski, D. Kissinger, G. Fischer, and L. R.
Schreiber, “30 GHz-voltage controlled oscillator operating at 4 K,” Review
of Scientific Instruments, vol. 89, no. 11. AIP Publishing, 2018.
ista: Hollmann A, Jirovec D, Kucharski M, Kissinger D, Fischer G, Schreiber LR.
2018. 30 GHz-voltage controlled oscillator operating at 4 K. Review of Scientific
Instruments. 89(11), 114701.
mla: Hollmann, Arne, et al. “30 GHz-Voltage Controlled Oscillator Operating at 4
K.” Review of Scientific Instruments, vol. 89, no. 11, 114701, AIP Publishing,
2018, doi:10.1063/1.5038258.
short: A. Hollmann, D. Jirovec, M. Kucharski, D. Kissinger, G. Fischer, L.R. Schreiber,
Review of Scientific Instruments 89 (2018).
date_created: 2019-01-10T14:22:23Z
date_published: 2018-11-01T00:00:00Z
date_updated: 2024-03-27T23:30:26Z
day: '01'
department:
- _id: GeKa
doi: 10.1063/1.5038258
external_id:
arxiv:
- '1804.09522'
isi:
- '000451735700054'
intvolume: ' 89'
isi: 1
issue: '11'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1804.09522
month: '11'
oa: 1
oa_version: Preprint
publication: Review of Scientific Instruments
publication_identifier:
issn:
- '00346748'
publication_status: published
publisher: AIP Publishing
quality_controlled: '1'
related_material:
record:
- id: '10058'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: 30 GHz-voltage controlled oscillator operating at 4 K
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 89
year: '2018'
...
---
_id: '6263'
abstract:
- lang: eng
text: 'Antibiotic resistance can emerge spontaneously through genomic mutation and render
treatment ineffective. To counteract this process, in addition to the discovery and
description of resistance mechanisms,a deeper understanding of resistanceevolvabilityand
its determinantsis needed. To address this challenge, this thesisuncoversnew genetic
determinants of resistance evolvability using a customized robotic setup,
exploressystematic ways in which resistance evolution is perturbed due to
dose-responsecharacteristics of drugs and mutation rate differences,and mathematically investigates
the evolutionary fate of one specific type of evolvability modifier -a stress-induced
mutagenesis allele.We find severalgenes which strongly inhibit or potentiate resistance evolution. In order
to identify them, we first developedan automated high-throughput feedback-controlled
protocol whichkeeps the population size and selection pressure approximately constant
for hundreds of cultures by dynamically re-diluting the cultures and adjusting the antibiotic
concentration. We implementedthis protocol on a customized liquid handling robot and
propagated 100 different gene deletion strains of Escherichia coliin triplicate for over 100
generations in tetracycline and in chloramphenicol, and comparedtheir adaptation rates.We find a diminishing returns pattern, where initially sensitive strains adapted more
compared to less sensitive ones. Our data uncover that deletions of certain genes
which do not affect mutation rate,including efflux pump components, a chaperone and
severalstructural and regulatory genes can strongly and reproducibly alterresistance evolution.
Sequencing analysis of evolved populations indicates that epistasis with resistance
mutations is the most likelyexplanation. This work could inspire treatment strategies in
which targeted inhibitors of evolvability mechanisms will be given alongside antibiotics to
slow down resistance evolution and extend theefficacy of antibiotics.We implemented astochasticpopulation genetics model,
toverifyways in which general properties, namely, dose-response characteristics of drugs and mutation rates, influence
evolutionary dynamics. In particular, under the exposure to antibiotics with shallow dose-response curves,bacteria have narrower distributions of fitness effects of new mutations.
We show that in silicothis also leads to slower resistance evolution. We
see and confirm with experiments that increased mutation rates, apart from speeding
up evolution, also leadto high reproducibility of phenotypic adaptation in a context
of continually strong selection pressure.Knowledge of these patterns can aid in predicting the dynamics of antibiotic
resistance evolutionand adapting treatment schemes accordingly.Focusing on a previously described type of evolvability modifier
–a stress-induced mutagenesis allele –we find conditions under which it can persist in a population under
periodic selectionakin to clinical treatment. We set up a deterministic
infinite populationcontinuous time model tracking the frequencies of a mutator and resistance allele and
evaluate various treatment schemes in how well they maintain a stress-induced
mutator allele. In particular,a high diversity of stresses is crucial for the persistence
of the mutator allele. This leads to a general trade-off where exactly those
diversifying treatment schemes which are likely to decrease levels of resistance could lead to stronger selection of highly
evolvable genotypes.In the long run, this work will lead to a deeper understanding of the genetic and cellular
mechanisms involved in antibiotic resistance evolution and could inspire new strategies
for slowing down its rate. '
acknowledged_ssus:
- _id: M-Shop
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Marta
full_name: Lukacisinova, Marta
id: 4342E402-F248-11E8-B48F-1D18A9856A87
last_name: Lukacisinova
orcid: 0000-0002-2519-8004
citation:
ama: Lukacisinova M. Genetic determinants of antibiotic resistance evolution. 2018.
doi:10.15479/AT:ISTA:th1072
apa: Lukacisinova, M. (2018). Genetic determinants of antibiotic resistance evolution.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th1072
chicago: Lukacisinova, Marta. “Genetic Determinants of Antibiotic Resistance Evolution.”
Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th1072.
ieee: M. Lukacisinova, “Genetic determinants of antibiotic resistance evolution,”
Institute of Science and Technology Austria, 2018.
ista: Lukacisinova M. 2018. Genetic determinants of antibiotic resistance evolution.
Institute of Science and Technology Austria.
mla: Lukacisinova, Marta. Genetic Determinants of Antibiotic Resistance Evolution.
Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th1072.
short: M. Lukacisinova, Genetic Determinants of Antibiotic Resistance Evolution,
Institute of Science and Technology Austria, 2018.
date_created: 2019-04-09T13:57:15Z
date_published: 2018-12-28T00:00:00Z
date_updated: 2023-09-22T09:20:37Z
day: '28'
ddc:
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