eprintid: 37472
rev_number: 27
eprint_status: archive
userid: 9334
dir: disk0/00/03/74/72
datestamp: 2025-10-27 14:31:27
lastmod: 2025-10-30 18:08:46
status_changed: 2025-10-27 14:31:27
type: doctoralThesis
metadata_visibility: show
creators_name: Tran, Mai Phuong
title: Genetic Encoding of Function: From DNA Segregation to Synthetic Cytoskeletons
subjects: ddc-570
subjects: ddc-620
subjects: ddc-660
divisions: i-160001
adv_faculty: af-19
cterms_swd: Synthetische Biologie
cterms_swd: DNS-Origami
cterms_swd: RNS
cterms_swd: Lipidmembran
abstract: Synthetic cells provide a powerful platform to explore the origins and principles of life, and hold promise for transformative applications in biotechnology. Among life’s features, evolvability is the central landmark to be engineered for life to emerge from non-living matter. However, there is currently no general strategy for the programmable segregation of genetic material, and structural components like cytoskeletons are rarely expressed in situ, limiting their evolvability.
In the first part, I develop a DNA-based module for programmable spatial segregation of information. Using DNA motifs that undergo liquid-liquid phase separation, DNA droplets can be induced to split via enzymatic or light triggers. When confined in synthetic compartments, their segregation kinetics and spatial behavior become sequence- and environment-dependent. A lattice-based theoretical model reproduces key features of the dynamics and helps explain how confinement influences segregation.
In the second part, I demonstrate the in situ expression of RNA origami cytoskeletons inside lipid vesicles. These co-transcriptionally folded structures self-assemble into nanotubes that bind and deform membranes. Sequence mutations modulate stiffness and morphology of the nanotubes, as shown experimentally and supported by coarse-grained molecular dynamics simulations that link sequence-level changes to mechanical responses.
By implementing nucleic acid nanostructures which give rise to microscale phenotypes, these systems create minimal genotype–phenotype couplings. This enables genetically encoded behaviors that are more readily selectable and thus more compatible with evolution.
date: 2025
id_scheme: DOI
id_number: 10.11588/heidok.00037472
ppn_swb: 1939785332
own_urn: urn:nbn:de:bsz:16-heidok-374724
date_accepted: 2025-10-14
advisor: HASH(0x55b5130e98c8)
language: eng
bibsort: TRANMAIPGENETICENC20251014
full_text_status: public
place_of_pub: Heidelberg
citation:   Tran, Mai Phuong  (2025) Genetic Encoding of Function: From DNA Segregation to Synthetic Cytoskeletons.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/37472/1/tran_thesis_full.pdf