---
_id: '8341'
abstract:
- lang: eng
text: "One of the most striking hallmarks of the eukaryotic cell is the presence
of intracellular vesicles and organelles. Each of these membrane-enclosed compartments
has a distinct composition of lipids and proteins, which is essential for accurate
membrane traffic and homeostasis. Interestingly, their biochemical identities
are achieved with the help\r\nof small GTPases of the Rab family, which cycle
between GDP- and GTP-bound forms on the selected membrane surface. While this
activity switch is well understood for an individual protein, how Rab GTPases
collectively transition between states to generate decisive signal propagation
in space and time is unclear. In my PhD thesis, I present\r\nin vitro reconstitution
experiments with theoretical modeling to systematically study a minimal Rab5 activation
network from bottom-up. We find that positive feedback based on known molecular
interactions gives rise to bistable GTPase activity switching on system’s scale.
Furthermore, we determine that collective transition near the critical\r\npoint
is intrinsically stochastic and provide evidence that the inactive Rab5 abundance
on the membrane can shape the network response. Finally, we demonstrate that collective
switching can spread on the lipid bilayer as a traveling activation wave, representing
a possible emergent activity pattern in endosomal maturation. Together, our\r\nfindings
reveal new insights into the self-organization properties of signaling networks
away from chemical equilibrium. Our work highlights the importance of systematic
characterization of biochemical systems in well-defined physiological conditions.
This way, we were able to answer long-standing open questions in the field and
close the gap between regulatory processes on a molecular scale and emergent responses
on system’s level."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: NanoFab
acknowledgement: My thanks goes to the Loose lab members, BioImaging, Life Science
and Nanofabrication Facilities and the wonderful international community at IST
for sharing this experience with me.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Urban
full_name: Bezeljak, Urban
id: 2A58201A-F248-11E8-B48F-1D18A9856A87
last_name: Bezeljak
orcid: 0000-0003-1365-5631
citation:
ama: Bezeljak U. In vitro reconstitution of a Rab activation switch. 2020. doi:10.15479/AT:ISTA:8341
apa: Bezeljak, U. (2020). In vitro reconstitution of a Rab activation switch.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8341
chicago: Bezeljak, Urban. “In Vitro Reconstitution of a Rab Activation Switch.”
Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8341.
ieee: U. Bezeljak, “In vitro reconstitution of a Rab activation switch,” Institute
of Science and Technology Austria, 2020.
ista: Bezeljak U. 2020. In vitro reconstitution of a Rab activation switch. Institute
of Science and Technology Austria.
mla: Bezeljak, Urban. In Vitro Reconstitution of a Rab Activation Switch.
Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8341.
short: U. Bezeljak, In Vitro Reconstitution of a Rab Activation Switch, Institute
of Science and Technology Austria, 2020.
date_created: 2020-09-08T08:53:53Z
date_published: 2020-09-08T00:00:00Z
date_updated: 2023-09-07T13:17:06Z
day: '08'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: MaLo
doi: 10.15479/AT:ISTA:8341
file:
- access_level: closed
checksum: 70871b335a595252a66c6bbf0824fb02
content_type: application/x-zip-compressed
creator: dernst
date_created: 2020-09-08T09:00:29Z
date_updated: 2021-09-16T12:49:12Z
file_id: '8342'
file_name: 2020_Urban_Bezeljak_Thesis_TeX.zip
file_size: 65246782
relation: source_file
- access_level: open_access
checksum: 59a62275088b00b7241e6ff4136434c7
content_type: application/pdf
creator: dernst
date_created: 2020-09-08T09:00:27Z
date_updated: 2021-09-16T12:49:12Z
file_id: '8343'
file_name: 2020_Urban_Bezeljak_Thesis.pdf
file_size: 31259058
relation: main_file
file_date_updated: 2021-09-16T12:49:12Z
has_accepted_license: '1'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '215'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7580'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Martin
full_name: Loose, Martin
id: 462D4284-F248-11E8-B48F-1D18A9856A87
last_name: Loose
orcid: 0000-0001-7309-9724
title: In vitro reconstitution of a Rab activation switch
tmp:
image: /images/cc_by_nc_sa.png
legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
BY-NC-SA 4.0)
short: CC BY-NC-SA (4.0)
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...