---
_id: '5914'
abstract:
- lang: eng
text: With the advent of optogenetics, it became possible to change the activity
of a targeted population of neurons in a temporally controlled manner. To combine
the advantages of 60-channel in vivo tetrode recording and laser-based optogenetics,
we have developed a closed-loop recording system that allows for the actual electrophysiological
signal to be used as a trigger for the laser light mediating the optogenetic intervention.
We have optimized the weight, size, and shape of the corresponding implant to
make it compatible with the size, force, and movements of a behaving mouse, and
we have shown that the system can efficiently block sharp wave ripple (SWR) events
using those events themselves as a trigger. To demonstrate the full potential
of the optogenetic recording system we present a pilot study addressing the contribution
of SWR events to learning in a complex behavioral task.
article_number: e0087
article_processing_charge: No
author:
- first_name: Dámaris K
full_name: Rangel Guerrero, Dámaris K
id: 4871BCE6-F248-11E8-B48F-1D18A9856A87
last_name: Rangel Guerrero
orcid: 0000-0002-8602-4374
- first_name: James G.
full_name: Donnett, James G.
last_name: Donnett
- first_name: Jozsef L
full_name: Csicsvari, Jozsef L
id: 3FA14672-F248-11E8-B48F-1D18A9856A87
last_name: Csicsvari
orcid: 0000-0002-5193-4036
- first_name: Krisztián
full_name: Kovács, Krisztián
id: 2AB5821E-F248-11E8-B48F-1D18A9856A87
last_name: Kovács
orcid: 0000-0001-6251-1007
citation:
ama: 'Rangel Guerrero DK, Donnett JG, Csicsvari JL, Kovács K. Tetrode recording
from the hippocampus of behaving mice coupled with four-point-irradiation closed-loop
optogenetics: A technique to study the contribution of Hippocampal SWR events
to learning. eNeuro. 2018;5(4). doi:10.1523/ENEURO.0087-18.2018'
apa: 'Rangel Guerrero, D. K., Donnett, J. G., Csicsvari, J. L., & Kovács, K.
(2018). Tetrode recording from the hippocampus of behaving mice coupled with four-point-irradiation
closed-loop optogenetics: A technique to study the contribution of Hippocampal
SWR events to learning. ENeuro. Society of Neuroscience. https://doi.org/10.1523/ENEURO.0087-18.2018'
chicago: 'Rangel Guerrero, Dámaris K, James G. Donnett, Jozsef L Csicsvari, and
Krisztián Kovács. “Tetrode Recording from the Hippocampus of Behaving Mice Coupled
with Four-Point-Irradiation Closed-Loop Optogenetics: A Technique to Study the
Contribution of Hippocampal SWR Events to Learning.” ENeuro. Society of
Neuroscience, 2018. https://doi.org/10.1523/ENEURO.0087-18.2018.'
ieee: 'D. K. Rangel Guerrero, J. G. Donnett, J. L. Csicsvari, and K. Kovács, “Tetrode
recording from the hippocampus of behaving mice coupled with four-point-irradiation
closed-loop optogenetics: A technique to study the contribution of Hippocampal
SWR events to learning,” eNeuro, vol. 5, no. 4. Society of Neuroscience,
2018.'
ista: 'Rangel Guerrero DK, Donnett JG, Csicsvari JL, Kovács K. 2018. Tetrode recording
from the hippocampus of behaving mice coupled with four-point-irradiation closed-loop
optogenetics: A technique to study the contribution of Hippocampal SWR events
to learning. eNeuro. 5(4), e0087.'
mla: 'Rangel Guerrero, Dámaris K., et al. “Tetrode Recording from the Hippocampus
of Behaving Mice Coupled with Four-Point-Irradiation Closed-Loop Optogenetics:
A Technique to Study the Contribution of Hippocampal SWR Events to Learning.”
ENeuro, vol. 5, no. 4, e0087, Society of Neuroscience, 2018, doi:10.1523/ENEURO.0087-18.2018.'
short: D.K. Rangel Guerrero, J.G. Donnett, J.L. Csicsvari, K. Kovács, ENeuro 5 (2018).
date_created: 2019-02-03T22:59:16Z
date_published: 2018-07-27T00:00:00Z
date_updated: 2024-03-28T23:30:10Z
day: '27'
ddc:
- '570'
department:
- _id: JoCs
doi: 10.1523/ENEURO.0087-18.2018
ec_funded: 1
external_id:
isi:
- '000443994700007'
file:
- access_level: open_access
checksum: f4915d45fc7ad4648b7b7a13fdecca01
content_type: application/pdf
creator: dernst
date_created: 2019-02-05T12:48:36Z
date_updated: 2020-07-14T12:47:13Z
file_id: '5921'
file_name: 2018_ENeuro_Guerrero.pdf
file_size: 3746884
relation: main_file
file_date_updated: 2020-07-14T12:47:13Z
has_accepted_license: '1'
intvolume: ' 5'
isi: 1
issue: '4'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 257D4372-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I2072-B27
name: Interneuron plasticity during spatial learning
publication: eNeuro
publication_status: published
publisher: Society of Neuroscience
quality_controlled: '1'
related_material:
record:
- id: '6849'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: 'Tetrode recording from the hippocampus of behaving mice coupled with four-point-irradiation
closed-loop optogenetics: A technique to study the contribution of Hippocampal SWR
events to learning'
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 5
year: '2018'
...
---
_id: '402'
abstract:
- lang: eng
text: During metastasis, malignant cells escape the primary tumor, intravasate lymphatic
vessels, and reach draining sentinel lymph nodes before they colonize distant
organs via the blood circulation. Although lymph node metastasis in cancer patients
correlates with poor prognosis, evidence is lacking as to whether and how tumor
cells enter the bloodstream via lymph nodes. To investigate this question, we
delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells
into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated
the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without
involvement of the thoracic duct. These results suggest that the lymph node blood
vessels can serve as an exit route for systemic dissemination of cancer cells
in experimental mouse models. Whether this form of tumor cell spreading occurs
in cancer patients remains to be determined.
acknowledged_ssus:
- _id: Bio
acknowledgement: "M.B. was supported by the Cell Communication in Health and Disease
graduate study program of the Austrian Science Fund (FWF) and the Medical University
of Vienna. M.S. was supported by the European Research Council (grant ERC GA 281556)
and an FWF START award.\r\nWe thank C. Moussion for establishing the intralymphatic
injection at IST Austria and for providing anti-PNAd hybridoma supernatant, R. Förster
and A. Braun for sharing the intralymphatic injection technology, K. Vaahtomeri
for the lentiviral constructs, M. Hons for establishing in vivo multiphoton imaging,
the Sixt lab for intellectual input, M. Schunn for help with the design of the in
vivo experiments, F. Langer for technical assistance with the in vivo experiments,
the bioimaging facility of IST Austria for support, and R. Efferl for providing
the CT26 cell line."
article_processing_charge: No
article_type: original
author:
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Frank P
full_name: Assen, Frank P
id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87
last_name: Assen
orcid: 0000-0003-3470-6119
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Jun
full_name: Abe, Jun
last_name: Abe
- first_name: Helga
full_name: Schachner, Helga
last_name: Schachner
- first_name: Gabriele
full_name: Asfour, Gabriele
last_name: Asfour
- first_name: Zsuzsanna
full_name: Bagó Horváth, Zsuzsanna
last_name: Bagó Horváth
- first_name: Jens
full_name: Stein, Jens
last_name: Stein
- first_name: Pavel
full_name: Uhrin, Pavel
last_name: Uhrin
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Dontscho
full_name: Kerjaschki, Dontscho
last_name: Kerjaschki
citation:
ama: Brown M, Assen FP, Leithner AF, et al. Lymph node blood vessels provide exit
routes for metastatic tumor cell dissemination in mice. Science. 2018;359(6382):1408-1411.
doi:10.1126/science.aal3662
apa: Brown, M., Assen, F. P., Leithner, A. F., Abe, J., Schachner, H., Asfour, G.,
… Kerjaschki, D. (2018). Lymph node blood vessels provide exit routes for metastatic
tumor cell dissemination in mice. Science. American Association for the
Advancement of Science. https://doi.org/10.1126/science.aal3662
chicago: Brown, Markus, Frank P Assen, Alexander F Leithner, Jun Abe, Helga Schachner,
Gabriele Asfour, Zsuzsanna Bagó Horváth, et al. “Lymph Node Blood Vessels Provide
Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” Science.
American Association for the Advancement of Science, 2018. https://doi.org/10.1126/science.aal3662.
ieee: M. Brown et al., “Lymph node blood vessels provide exit routes for
metastatic tumor cell dissemination in mice,” Science, vol. 359, no. 6382.
American Association for the Advancement of Science, pp. 1408–1411, 2018.
ista: Brown M, Assen FP, Leithner AF, Abe J, Schachner H, Asfour G, Bagó Horváth
Z, Stein J, Uhrin P, Sixt MK, Kerjaschki D. 2018. Lymph node blood vessels provide
exit routes for metastatic tumor cell dissemination in mice. Science. 359(6382),
1408–1411.
mla: Brown, Markus, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic
Tumor Cell Dissemination in Mice.” Science, vol. 359, no. 6382, American
Association for the Advancement of Science, 2018, pp. 1408–11, doi:10.1126/science.aal3662.
short: M. Brown, F.P. Assen, A.F. Leithner, J. Abe, H. Schachner, G. Asfour, Z.
Bagó Horváth, J. Stein, P. Uhrin, M.K. Sixt, D. Kerjaschki, Science 359 (2018)
1408–1411.
date_created: 2018-12-11T11:46:16Z
date_published: 2018-03-23T00:00:00Z
date_updated: 2024-03-28T23:30:09Z
day: '23'
department:
- _id: MiSi
doi: 10.1126/science.aal3662
ec_funded: 1
external_id:
isi:
- '000428043600047'
pmid:
- '29567714'
intvolume: ' 359'
isi: 1
issue: '6382'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1126/science.aal3662
month: '03'
oa: 1
oa_version: Published Version
page: 1408 - 1411
pmid: 1
project:
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Y 564-B12
name: Cytoskeletal force generation and transduction of leukocytes (FWF)
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
(EU)
publication: Science
publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '7428'
quality_controlled: '1'
related_material:
record:
- id: '6947'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination
in mice
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 359
year: '2018'
...
---
_id: '395'
abstract:
- lang: eng
text: 'Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping
with other neurological conditions. Despite the remarkable number of scientific
breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders
(e.g. autism spectrum disorder, intellectual disability, epilepsy) remains a great
challenge. Recent advancements in geno mics, like whole-exome or whole-genome
sequencing, have enabled scientists to identify numerous mutations underlying
neurodevelopmental disorders. Given the few hundred risk genes that were discovered,
the etiological variability and the heterogeneous phenotypic outcomes, the need
for genotype -along with phenotype- based diagnosis of individual patients becomes
a requisite. Driven by this rationale, in a previous study our group described
mutations, identified via whole - exome sequencing, in the gene BCKDK – encoding
for a key regulator of branched chain amin o acid (BCAA) catabolism - as a cause
of ASD. Following up on the role of BCAAs, in the study described here we show
that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter
localized mainly at the blood brain barrier (BBB), has an essential role in maintaining
normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial
cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation
and severe neurolo gical abnormalities. Additionally, deletion of Slc7a5 from
the neural progenitor cell population leads to microcephaly. Interestingly, we
demonstrate that BCAA intracerebroventricular administration ameliorates abnormal
behaviors in adult mutant mice. Furthermore, whole - exome sequencing of patients
diagnosed with neurological dis o r ders helped us identify several patients with
autistic traits, microcephaly and motor delay carrying deleterious homozygous
mutations in the SLC7A5 gene. In conclusion, our data elucidate a neurological
syndrome defined by SLC7A5 mutations and support an essential role for t he BCAA
s in human bra in function. Together with r ecent studies (described in chapter
two) that have successfully made the transition into clinical practice, our findings
on the role of B CAAs might have a crucial impact on the development of novel
individualized therapeutic strategies for ASD. '
acknowledged_ssus:
- _id: PreCl
- _id: EM-Fac
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Dora-Clara
full_name: Tarlungeanu, Dora-Clara
id: 2ABCE612-F248-11E8-B48F-1D18A9856A87
last_name: Tarlungeanu
citation:
ama: Tarlungeanu D-C. The branched chain amino acids in autism spectrum disorders
. 2018. doi:10.15479/AT:ISTA:th_992
apa: Tarlungeanu, D.-C. (2018). The branched chain amino acids in autism spectrum
disorders . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_992
chicago: Tarlungeanu, Dora-Clara. “The Branched Chain Amino Acids in Autism Spectrum
Disorders .” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_992.
ieee: D.-C. Tarlungeanu, “The branched chain amino acids in autism spectrum disorders
,” Institute of Science and Technology Austria, 2018.
ista: Tarlungeanu D-C. 2018. The branched chain amino acids in autism spectrum disorders
. Institute of Science and Technology Austria.
mla: Tarlungeanu, Dora-Clara. The Branched Chain Amino Acids in Autism Spectrum
Disorders . Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_992.
short: D.-C. Tarlungeanu, The Branched Chain Amino Acids in Autism Spectrum Disorders
, Institute of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:46:14Z
date_published: 2018-03-01T00:00:00Z
date_updated: 2023-09-07T12:38:59Z
day: '01'
ddc:
- '570'
- '616'
degree_awarded: PhD
department:
- _id: GaNo
doi: 10.15479/AT:ISTA:th_992
file:
- access_level: closed
checksum: 9f5231c96e0ad945040841a8630232da
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: dernst
date_created: 2019-04-05T09:19:17Z
date_updated: 2021-02-11T23:30:15Z
embargo_to: open_access
file_id: '6217'
file_name: 2018_Thesis_Tarlungeanu_source.docx
file_size: 43684035
relation: source_file
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checksum: 0c33c370aa2010df5c552db57a6d01e9
content_type: application/pdf
creator: dernst
date_created: 2019-04-05T09:19:17Z
date_updated: 2021-02-11T11:17:16Z
embargo: 2018-03-15
file_id: '6218'
file_name: 2018_Thesis_Tarlungeanu.pdf
file_size: 30511532
relation: main_file
file_date_updated: 2021-02-11T23:30:15Z
has_accepted_license: '1'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: '88'
project:
- _id: 25473368-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: F03523
name: Transmembrane Transporters in Health and Disease
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '7434'
pubrep_id: '992'
related_material:
record:
- id: '1183'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
title: 'The branched chain amino acids in autism spectrum disorders '
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: '51'
abstract:
- lang: eng
text: Asymmetries have long been known about in the central nervous system. From
gross anatomical differences, such as the presence of the parapineal organ in
only one hemisphere of the developing zebrafish, to more subtle differences in
activity between both hemispheres, as seen in freely roaming animals or human
participants under PET and fMRI imaging analysis. The presence of asymmetries
has been demonstrated to have huge behavioural implications, with their disruption
often leading to the generation of neurological disorders, memory problems, changes
in personality, and in an organism's health and well-being. For my Ph.D. work
I aimed to tackle two important avenues of research. The first being the process
of input-side dependency in the hippocampus, with the goal of finding a key gene
responsible for its development (Gene X). The second project was to do with experience-induced
laterality formation in the hippocampus. Specifically, how laterality in the synapse
density of the CA1 stratum radiatum (s.r.) could be induced purely through environmental
enrichment. Through unilateral tracer injections into the CA3, I was able to selectively
measure the properties of synapses within the CA1 and investigate how they differed
based upon which hemisphere the presynaptic neurone originated. Having found the
existence of a previously unreported reversed (left-isomerism) i.v. mutant, through
morpholocal examination of labelled terminals in the CA1 s.r., I aimed to elucidate
a key gene responsible for the process of left or right determination of inputs
to the CA1 s.r.. This work relates to the previous finding of input-side dependent
asymmetry in the wild-type rodent, where the origin of the projecting neurone
to the CA1 will determine the morphology of a synapse, to a greater degree than
the hemisphere in which the projection terminates. Using left- and right-isomerism
i.v. mice, in combination with whole genome sequence analysis, I highlight Ena/VASP-like
(Evl) as a potential target for Gene X. In relation to this topic, I also highlight
my work in the recently published paper of how knockout of PirB can lead to a
lack of input-side dependency in the murine hippocampus. For the second question,
I show that the environmental enrichment paradigm will lead to an asymmetry in
the synapse densities in the hippocampus of mice. I also highlight that the nature
of the enrichment is of less consequence than the process of enrichment itself.
I demonstrate that the CA3 region will dramatically alter its projection targets,
in relation to environmental stimulation, with the asymmetry in synaptic density,
caused by enrichment, relying heavily on commissural fibres. I also highlight
the vital importance of input-side dependent asymmetry, as a necessary component
of experience-dependent laterality formation in the CA1 s.r.. However, my results
suggest that it isn't the only cause, as there appears to be a CA1 dependent mechanism
also at play. Upon further investigation, I highlight the significant, and highly
important, finding that the changes seen in the CA1 s.r. were predominantly caused
through projections from the left-CA3, with the right-CA3 having less involvement
in this mechanism.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Matthew J
full_name: Case, Matthew J
id: 44B7CA5A-F248-11E8-B48F-1D18A9856A87
last_name: Case
citation:
ama: 'Case MJ. From the left to the right: A tale of asymmetries, environments,
and hippocampal development. 2018. doi:10.15479/AT:ISTA:th_1032'
apa: 'Case, M. J. (2018). From the left to the right: A tale of asymmetries,
environments, and hippocampal development. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT:ISTA:th_1032'
chicago: 'Case, Matthew J. “From the Left to the Right: A Tale of Asymmetries, Environments,
and Hippocampal Development.” Institute of Science and Technology Austria, 2018.
https://doi.org/10.15479/AT:ISTA:th_1032.'
ieee: 'M. J. Case, “From the left to the right: A tale of asymmetries, environments,
and hippocampal development,” Institute of Science and Technology Austria, 2018.'
ista: 'Case MJ. 2018. From the left to the right: A tale of asymmetries, environments,
and hippocampal development. Institute of Science and Technology Austria.'
mla: 'Case, Matthew J. From the Left to the Right: A Tale of Asymmetries, Environments,
and Hippocampal Development. Institute of Science and Technology Austria,
2018, doi:10.15479/AT:ISTA:th_1032.'
short: 'M.J. Case, From the Left to the Right: A Tale of Asymmetries, Environments,
and Hippocampal Development, Institute of Science and Technology Austria, 2018.'
date_created: 2018-12-11T11:44:22Z
date_published: 2018-06-27T00:00:00Z
date_updated: 2023-09-07T12:39:22Z
day: '27'
ddc:
- '571'
- '576'
degree_awarded: PhD
department:
- _id: RySh
doi: 10.15479/AT:ISTA:th_1032
file:
- access_level: closed
checksum: dcc7b55619d8509dd62b8e99d6cdee44
content_type: application/msword
creator: dernst
date_created: 2019-04-09T07:16:26Z
date_updated: 2021-02-11T23:30:13Z
embargo_to: open_access
file_id: '6251'
file_name: 2018_Thesis_Case_Source.doc
file_size: 141270528
relation: source_file
- access_level: open_access
checksum: f69fdd5c8709c4e618aa8c1a1221153d
content_type: application/pdf
creator: dernst
date_created: 2019-04-09T07:16:23Z
date_updated: 2021-02-11T11:17:14Z
embargo: 2019-07-05
file_id: '6252'
file_name: 2018_Thesis_Case.pdf
file_size: 15193621
relation: main_file
file_date_updated: 2021-02-11T23:30:13Z
has_accepted_license: '1'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: '186'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '8003'
pubrep_id: '1032'
related_material:
record:
- id: '682'
relation: part_of_dissertation
status: public
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: 'From the left to the right: A tale of asymmetries, environments, and hippocampal
development'
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...
---
_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
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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
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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:
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publisher: Institute of Science and Technology Austria
publist_id: '8047'
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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
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month: '10'
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page: '95'
publication_identifier:
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publication_status: published
publisher: Institute of Science and Technology Austria
pubrep_id: '1055'
related_material:
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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'
...