---
_id: '11193'
abstract:
- lang: eng
text: "The infiltration of immune cells into tissues underlies the establishment
of tissue-resident\r\nmacrophages and responses to infections and tumors. However,
the mechanisms immune\r\ncells utilize to collectively migrate through tissue
barriers in vivo are not yet well understood.\r\nIn this thesis, I describe two
mechanisms that Drosophila immune cells (hemocytes) use to\r\novercome the tissue
barrier of the germband in the embryo. One strategy is the strengthening\r\nof
the actin cortex through developmentally controlled transcriptional regulation
induced by\r\nthe Drosophila proto-oncogene family member Dfos, which I show in
Chapter 2. Dfos induces\r\nexpression of the tetraspanin TM4SF and the filamin
Cher leading to higher levels of the\r\nactivated formin Dia at the cortex and
increased cortical F-actin. This enhanced cortical\r\nstrength allows hemocytes
to overcome the physical resistance of the surrounding tissue and\r\ntranslocate
their nucleus to move forward. This mechanism affects the speed of migration\r\nwhen
hemocytes face a confined environment in vivo.\r\nAnother aspect of the invasion
process is the initial step of the leading hemocytes entering\r\nthe tissue, which
potentially guides the follower cells. In Chapter 3, I describe a novel\r\nsubpopulation
of hemocytes activated by BMP signaling prior to tissue invasion that leads\r\npenetration
into the germband. Hemocytes that are deficient in BMP signaling activation\r\nshow
impaired persistence at the tissue entry, while their migration speed remains\r\nunaffected.\r\nThis
suggests that there might be different mechanisms controlling immune cell migration\r\nwithin
the confined environment in vivo, one of these being the general ability to overcome\r\nthe
resistance of the surrounding tissue and another affecting the order of hemocytes
that\r\ncollectively invade the tissue in a stream of individual cells.\r\nTogether,
my findings provide deeper insights into transcriptional changes in immune\r\ncells
that enable efficient tissue invasion and pave the way for future studies investigating
the\r\nearly colonization of tissues by macrophages in higher organisms. Moreover,
they extend the\r\ncurrent view of Drosophila immune cell heterogeneity and point
toward a potentially\r\nconserved role for canonical BMP signaling in specifying
immune cells that lead the migration\r\nof tissue resident macrophages during
embryogenesis."
acknowledged_ssus:
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Stephanie
full_name: Wachner, Stephanie
id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87
last_name: Wachner
citation:
ama: Wachner S. Transcriptional regulation by Dfos and BMP-signaling support tissue
invasion of Drosophila immune cells. 2022. doi:10.15479/at:ista:11193
apa: Wachner, S. (2022). Transcriptional regulation by Dfos and BMP-signaling
support tissue invasion of Drosophila immune cells. Institute of Science and
Technology Austria. https://doi.org/10.15479/at:ista:11193
chicago: Wachner, Stephanie. “Transcriptional Regulation by Dfos and BMP-Signaling
Support Tissue Invasion of Drosophila Immune Cells.” Institute of Science and
Technology Austria, 2022. https://doi.org/10.15479/at:ista:11193.
ieee: S. Wachner, “Transcriptional regulation by Dfos and BMP-signaling support
tissue invasion of Drosophila immune cells,” Institute of Science and Technology
Austria, 2022.
ista: Wachner S. 2022. Transcriptional regulation by Dfos and BMP-signaling support
tissue invasion of Drosophila immune cells. Institute of Science and Technology
Austria.
mla: Wachner, Stephanie. Transcriptional Regulation by Dfos and BMP-Signaling
Support Tissue Invasion of Drosophila Immune Cells. Institute of Science and
Technology Austria, 2022, doi:10.15479/at:ista:11193.
short: S. Wachner, Transcriptional Regulation by Dfos and BMP-Signaling Support
Tissue Invasion of Drosophila Immune Cells, Institute of Science and Technology
Austria, 2022.
date_created: 2022-04-20T08:59:07Z
date_published: 2022-04-20T00:00:00Z
date_updated: 2023-09-19T10:15:54Z
day: '20'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: DaSi
doi: 10.15479/at:ista:11193
file:
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date_updated: 2023-04-21T22:30:03Z
embargo: 2023-04-20
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creator: cchlebak
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file_name: Thesis_Stephanie_Wachner_20200414.zip
file_size: 65864612
relation: source_file
file_date_updated: 2023-04-21T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: '170'
project:
- _id: 26199CA4-B435-11E9-9278-68D0E5697425
grant_number: '24800'
name: Tissue barrier penetration is crucial for immunity and metastasis
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '10614'
relation: part_of_dissertation
status: public
- id: '544'
relation: part_of_dissertation
status: public
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 by Dfos and BMP-signaling support tissue invasion
of Drosophila immune 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: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2022'
...
---
_id: '8983'
abstract:
- lang: eng
text: Metabolic adaptation is a critical feature of migrating cells. It tunes the
metabolic programs of migrating cells to allow them to efficiently exert their
crucial roles in development, inflammatory responses and tumor metastasis. Cell
migration through physically challenging contexts requires energy. However, how
the metabolic reprogramming that underlies in vivo cell invasion is controlled
is still unanswered. In my PhD project, I identify a novel conserved metabolic
shift in Drosophila melanogaster immune cells that by modulating their bioenergetic
potential controls developmentally programmed tissue invasion. We show that this
regulation requires a novel conserved nuclear protein, named Atossa. Atossa enhances
the transcription of a set of proteins, including an RNA helicase Porthos and
two metabolic enzymes, each of which increases the tissue invasion of leading
Drosophila macrophages and can rescue the atossa mutant phenotype. Porthos selectively
regulates the translational efficiency of a subset of mRNAs containing a 5’-UTR
cis-regulatory TOP-like sequence. These 5’TOPL mRNA targets encode mitochondrial-related
proteins, including subunits of mitochondrial oxidative phosphorylation (OXPHOS)
components III and V and other metabolic-related proteins. Porthos powers up mitochondrial
OXPHOS to engender a sufficient ATP supply, which is required for tissue invasion
of leading macrophages. Atossa’s two vertebrate orthologs rescue the invasion
defect. In my PhD project, I elucidate that Atossa displays a conserved developmental
metabolic control to modulate metabolic capacities and the cellular energy state,
through altered transcription and translation, to aid the tissue infiltration
of leading cells into energy demanding barriers.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: E-Lib
- _id: CampIT
acknowledgement: Also, I would like to express my appreciation and thanks to the Bioimaging
facility, LSF, GSO, library, and IT people at IST Austria.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Shamsi
full_name: Emtenani, Shamsi
id: 49D32318-F248-11E8-B48F-1D18A9856A87
last_name: Emtenani
orcid: 0000-0001-6981-6938
citation:
ama: Emtenani S. Metabolic regulation of Drosophila macrophage tissue invasion.
2020. doi:10.15479/AT:ISTA:8983
apa: Emtenani, S. (2020). Metabolic regulation of Drosophila macrophage tissue
invasion. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8983
chicago: Emtenani, Shamsi. “Metabolic Regulation of Drosophila Macrophage Tissue
Invasion.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8983.
ieee: S. Emtenani, “Metabolic regulation of Drosophila macrophage tissue invasion,”
Institute of Science and Technology Austria, 2020.
ista: Emtenani S. 2020. Metabolic regulation of Drosophila macrophage tissue invasion.
Institute of Science and Technology Austria.
mla: Emtenani, Shamsi. Metabolic Regulation of Drosophila Macrophage Tissue Invasion.
Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8983.
short: S. Emtenani, Metabolic Regulation of Drosophila Macrophage Tissue Invasion,
Institute of Science and Technology Austria, 2020.
date_created: 2020-12-30T15:41:26Z
date_published: 2020-12-30T00:00:00Z
date_updated: 2023-09-07T13:24:17Z
day: '30'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: DaSi
doi: 10.15479/AT:ISTA:8983
file:
- access_level: open_access
checksum: ec2797ab7a6f253b35df0572b36d1b43
content_type: application/pdf
creator: semtenan
date_created: 2020-12-30T15:34:01Z
date_updated: 2021-12-31T23:30:04Z
embargo: 2021-12-30
file_id: '8984'
file_name: Thesis_Shamsi_Emtenani_pdfA.pdf
file_size: 10848175
relation: main_file
- access_level: closed
checksum: cc30e6608a9815414024cf548dff3b3a
content_type: application/pdf
creator: semtenan
date_created: 2020-12-30T15:37:36Z
date_updated: 2021-12-31T23:30:04Z
embargo_to: open_access
file_id: '8985'
file_name: Thesis_Shamsi_Emtenani_source file.pdf
file_size: 10073648
relation: source_file
file_date_updated: 2021-12-31T23:30:04Z
has_accepted_license: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: '141'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '8557'
relation: part_of_dissertation
status: public
- id: '6187'
relation: part_of_dissertation
status: public
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: Metabolic regulation of Drosophila macrophage tissue invasion
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '6546'
abstract:
- lang: eng
text: "Invasive migration plays a crucial role not only during development and homeostasis
but also in pathological states, such as tumor metastasis. Drosophila macrophage
migration into the extended germband is an interesting system to study invasive
migration. It carries similarities to immune cell transmigration and cancer cell
invasion, therefore studying this process could also bring new understanding of
invasion in higher organisms. In our work, we uncover a highly conserved member
of the major facilitator family that plays a role in tissue invasion through regulation
of glycosylation on a subgroup of proteins and/or by aiding the precise timing
of DN-Cadherin downregulation. \r\n\r\nAberrant display of the truncated core1
O-glycan T-antigen is a common feature of human cancer cells that correlates with
metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages
is involved in their developmentally programmed tissue invasion. Higher macrophage
T-antigen levels require an atypical major facilitator superfamily (MFS) member
that we named Minerva which enables macrophage dissemination and invasion. We
characterize for the first time the T and Tn glycoform O-glycoproteome of the
Drosophila melanogaster embryo, and determine that Minerva increases the presence
of T-antigen on proteins in pathways previously linked to cancer, most strongly
on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue
entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration
and T-antigen glycosylation defects. We thus identify \r\na key conserved regulator
that orchestrates O-glycosylation on a protein subset to activate \r\na program
governing migration steps important for both development and cancer metastasis.
\r\n"
acknowledged_ssus:
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Katarina
full_name: Valosková, Katarina
id: 46F146FC-F248-11E8-B48F-1D18A9856A87
last_name: Valosková
citation:
ama: Valosková K. The role of a highly conserved major facilitator superfamily member
in Drosophila embryonic macrophage migration. 2019. doi:10.15479/AT:ISTA:6546
apa: Valosková, K. (2019). The role of a highly conserved major facilitator superfamily
member in Drosophila embryonic macrophage migration. Institute of Science
and Technology Austria. https://doi.org/10.15479/AT:ISTA:6546
chicago: Valosková, Katarina. “The Role of a Highly Conserved Major Facilitator
Superfamily Member in Drosophila Embryonic Macrophage Migration.” Institute of
Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6546.
ieee: K. Valosková, “The role of a highly conserved major facilitator superfamily
member in Drosophila embryonic macrophage migration,” Institute of Science and
Technology Austria, 2019.
ista: Valosková K. 2019. The role of a highly conserved major facilitator superfamily
member in Drosophila embryonic macrophage migration. Institute of Science and
Technology Austria.
mla: Valosková, Katarina. The Role of a Highly Conserved Major Facilitator Superfamily
Member in Drosophila Embryonic Macrophage Migration. Institute of Science
and Technology Austria, 2019, doi:10.15479/AT:ISTA:6546.
short: K. Valosková, The Role of a Highly Conserved Major Facilitator Superfamily
Member in Drosophila Embryonic Macrophage Migration, Institute of Science and
Technology Austria, 2019.
date_created: 2019-06-07T12:49:19Z
date_published: 2019-06-07T00:00:00Z
date_updated: 2023-09-19T10:15:54Z
day: '07'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: DaSi
doi: 10.15479/AT:ISTA:6546
file:
- access_level: closed
checksum: 68949c2d96210b45b981a23e9c9cd93c
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: khribikova
date_created: 2019-06-07T13:00:04Z
date_updated: 2020-07-14T12:47:33Z
embargo_to: open_access
file_id: '6549'
file_name: Katarina Valoskova_PhD thesis_final version.docx
file_size: 14110626
relation: source_file
- access_level: open_access
checksum: 555329cd76e196c96f5278c480ee2e6e
content_type: application/pdf
creator: khribikova
date_created: 2019-06-07T13:00:08Z
date_updated: 2021-02-11T11:17:14Z
embargo: 2020-06-07
file_id: '6550'
file_name: Katarina Valoskova_PhD thesis_final version.pdf
file_size: 10054156
relation: main_file
file_date_updated: 2021-02-11T11:17:14Z
has_accepted_license: '1'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: '141'
project:
- _id: 253CDE40-B435-11E9-9278-68D0E5697425
grant_number: '24283'
name: Examination of the role of a MFS transporter in the migration of Drosophila
immune cells
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '6187'
relation: part_of_dissertation
status: public
- id: '544'
relation: part_of_dissertation
status: public
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: The role of a highly conserved major facilitator superfamily member in Drosophila
embryonic macrophage migration
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2019'
...
---
_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
- access_level: open_access
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'
...