---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '21275'
abstract:
- lang: eng
text: DNA methylation is a primary layer of epigenetic modification that plays a
pivotal role in the regulation of development, aging, and cancer. The concurrent
activity of opposing enzymes that mediate DNA methylation and demethylation gives
rise to a biochemical cycle and active turnover of DNA methylation. While the
ensuing biochemical oscillations have been implicated in the regulation of cell
differentiation, their functional role and spatiotemporal dynamics are unknown.
In this work, we demonstrate that chromatin-mediated coupling between these local
biochemical cycles can lead to the emergence of phase-locked domains, regions
of locally synchronized turnover activity, whose coarsening is arrested by genomic
heterogeneity. We introduce a minimal model based on stochastic oscillators with
constrained long-range and nonreciprocal interactions, shaped by the local chromatin
organization. Through a combination of analytical theory and stochastic simulations,
we predict both the degree of synchronization and the typical size of emergent
phase-locked domains. We qualitatively test these predictions using single-cell
sequencing data. Our results show that DNA methylation turnover exhibits surprisingly
rich spatiotemporal patterns that may be used by cells to control cell differentiation.
acknowledgement: This project has received funding from the European Union's Horizon
2020 research and innovation programme under Grant Agreement No. 950349 and the
Marie Skłodowska-Curie Grant Agreement No. 101034413. The computations in this paper
were run in part on the the FASRC Cannon cluster supported by the FAS Division of
Science Research Computing Group at Harvard University and the cluster of the Max
Planck Institute for the Physics of Complex Systems.
article_number: '013018'
article_processing_charge: Yes
article_type: original
author:
- first_name: Fabrizio
full_name: Olmeda, Fabrizio
id: 69dbf5fb-8a76-11ed-866b-fb486d8b5689
last_name: Olmeda
- first_name: Misha
full_name: Gupta, Misha
last_name: Gupta
- first_name: Onurcan
full_name: Bektas, Onurcan
last_name: Bektas
- first_name: Steffen
full_name: Rulands, Steffen
last_name: Rulands
citation:
ama: Olmeda F, Gupta M, Bektas O, Rulands S. Spatiotemporal patterns of active epigenetic
turnover. PRX Life. 2026;4. doi:10.1103/89bj-79g5
apa: Olmeda, F., Gupta, M., Bektas, O., & Rulands, S. (2026). Spatiotemporal
patterns of active epigenetic turnover. PRX Life. American Physical Society.
https://doi.org/10.1103/89bj-79g5
chicago: Olmeda, Fabrizio, Misha Gupta, Onurcan Bektas, and Steffen Rulands. “Spatiotemporal
Patterns of Active Epigenetic Turnover.” PRX Life. American Physical Society,
2026. https://doi.org/10.1103/89bj-79g5.
ieee: F. Olmeda, M. Gupta, O. Bektas, and S. Rulands, “Spatiotemporal patterns of
active epigenetic turnover,” PRX Life, vol. 4. American Physical Society,
2026.
ista: Olmeda F, Gupta M, Bektas O, Rulands S. 2026. Spatiotemporal patterns of active
epigenetic turnover. PRX Life. 4, 013018.
mla: Olmeda, Fabrizio, et al. “Spatiotemporal Patterns of Active Epigenetic Turnover.”
PRX Life, vol. 4, 013018, American Physical Society, 2026, doi:10.1103/89bj-79g5.
short: F. Olmeda, M. Gupta, O. Bektas, S. Rulands, PRX Life 4 (2026).
corr_author: '1'
date_created: 2026-02-17T08:17:53Z
date_published: 2026-02-09T00:00:00Z
date_updated: 2026-02-24T06:54:32Z
day: '09'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1103/89bj-79g5
ec_funded: 1
file:
- access_level: open_access
checksum: df9776422862d1d02c66d98e2d620849
content_type: application/pdf
creator: dernst
date_created: 2026-02-24T06:53:05Z
date_updated: 2026-02-24T06:53:05Z
file_id: '21351'
file_name: 2026_PRXLife_Olmeda.pdf
file_size: 5857833
relation: main_file
success: 1
file_date_updated: 2026-02-24T06:53:05Z
has_accepted_license: '1'
intvolume: ' 4'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
project:
- _id: fc2ed2f7-9c52-11eb-aca3-c01059dda49c
call_identifier: H2020
grant_number: '101034413'
name: 'IST-BRIDGE: International postdoctoral program'
publication: PRX Life
publication_identifier:
eissn:
- 2835-8279
publication_status: published
publisher: American Physical Society
quality_controlled: '1'
status: public
title: Spatiotemporal patterns of active epigenetic turnover
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 4
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '21849'
abstract:
- lang: eng
text: The development of complex tissues relies on the precise assignment of cell
identity. At the molecular scale, this process depends on the deposition of epigenetic
modifications—such as methylation—that are regulated by complex biochemical networks
and occur at specific regions on the DNA and chromatin. Here we show that despite
the complexity of epigenetic regulation, dynamical scaling and self-similarity
of DNA methylation marks emerge in embryonic development. Drawing on single-cell
multi-omics experiments, super-resolution microscopy and statistical physics,
we demonstrate that these phenomena originate in dynamical feedback between DNA
methylation and the formation of nanoscale dynamic chromatin aggregates. These
nanoscale processes lead to genome-wide increase in DNA methylation marks following
a power law and self-similar correlation functions. Using this framework, we identify
methylation patterns that precede gene expression changes in embryonic symmetry
breaking. Our work identifies linear sequencing measurements as a laboratory to
study mesoscopic biophysical processes in vivo.
acknowledgement: We thank all members of the W.R. and S.R. laboratories, F. Piazza,
B. D. Simons, and F. Jülicher for helpful discussions. We thank M. Ciarchi for providing
annotations for the chromatin compartments. S.R. is a member of the Center for Nano
Science (CeNS). This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation programme
(grant agreement number 950349). Research in W.R.’s laboratory was supported by
the Biotechnology and Biological Sciences Research Council (BB/K010867/1), Wellcome
(095645/Z/11/Z) and the European Research Council (ERC) under the European Union’s
Horizon 2020 research and innovation programme (EpiCell lineage 882798). F.O. received
funding from the European Union’s Horizon 2020 research and innovation programme
under the Marie Skłodowska-Curie grant agreement number 101034413. Open access funding
provided by Max Planck Society.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Fabrizio
full_name: Olmeda, Fabrizio
id: 69dbf5fb-8a76-11ed-866b-fb486d8b5689
last_name: Olmeda
- first_name: Tim
full_name: Lohoff, Tim
last_name: Lohoff
- first_name: Ioannis
full_name: Kafetzopoulos, Ioannis
last_name: Kafetzopoulos
- first_name: Stephen J.
full_name: Clark, Stephen J.
last_name: Clark
- first_name: Laura
full_name: Benson, Laura
last_name: Benson
- first_name: Fatima
full_name: Santos, Fatima
last_name: Santos
- first_name: Felix
full_name: Krueger, Felix
last_name: Krueger
- first_name: Simon
full_name: Walker, Simon
last_name: Walker
- first_name: Wolf
full_name: Reik, Wolf
last_name: Reik
- first_name: Steffen
full_name: Rulands, Steffen
last_name: Rulands
citation:
ama: Olmeda F, Lohoff T, Kafetzopoulos I, et al. Scaling and self-similarity in
the formation of the embryonic epigenome. Nature Physics. 2026. doi:10.1038/s41567-026-03263-x
apa: Olmeda, F., Lohoff, T., Kafetzopoulos, I., Clark, S. J., Benson, L., Santos,
F., … Rulands, S. (2026). Scaling and self-similarity in the formation of the
embryonic epigenome. Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-026-03263-x
chicago: Olmeda, Fabrizio, Tim Lohoff, Ioannis Kafetzopoulos, Stephen J. Clark,
Laura Benson, Fatima Santos, Felix Krueger, Simon Walker, Wolf Reik, and Steffen
Rulands. “Scaling and Self-Similarity in the Formation of the Embryonic Epigenome.”
Nature Physics. Springer Nature, 2026. https://doi.org/10.1038/s41567-026-03263-x.
ieee: F. Olmeda et al., “Scaling and self-similarity in the formation of
the embryonic epigenome,” Nature Physics. Springer Nature, 2026.
ista: Olmeda F, Lohoff T, Kafetzopoulos I, Clark SJ, Benson L, Santos F, Krueger
F, Walker S, Reik W, Rulands S. 2026. Scaling and self-similarity in the formation
of the embryonic epigenome. Nature Physics.
mla: Olmeda, Fabrizio, et al. “Scaling and Self-Similarity in the Formation of the
Embryonic Epigenome.” Nature Physics, Springer Nature, 2026, doi:10.1038/s41567-026-03263-x.
short: F. Olmeda, T. Lohoff, I. Kafetzopoulos, S.J. Clark, L. Benson, F. Santos,
F. Krueger, S. Walker, W. Reik, S. Rulands, Nature Physics (2026).
date_created: 2026-05-10T22:02:16Z
date_published: 2026-04-29T00:00:00Z
date_updated: 2026-05-11T06:22:47Z
day: '29'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1038/s41567-026-03263-x
ec_funded: 1
has_accepted_license: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1038/s41567-026-03263-x
month: '04'
oa: 1
oa_version: Published Version
project:
- _id: fc2ed2f7-9c52-11eb-aca3-c01059dda49c
call_identifier: H2020
grant_number: '101034413'
name: 'IST-BRIDGE: International postdoctoral program'
publication: Nature Physics
publication_identifier:
eissn:
- 1745-2481
issn:
- 1745-2473
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Scaling and self-similarity in the formation of the embryonic epigenome
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
_id: '19670'
abstract:
- lang: eng
text: “Pasta alla Cacio e pepe” is a traditional Italian dish made with pasta, pecorino
cheese, and pepper. Despite its simple ingredient list, achieving the perfect
texture and creaminess of the sauce can be challenging. In this study, we systematically
explore the phase behavior of Cacio e pepe sauce, focusing on its stability at
increasing temperatures for various proportions of cheese, water, and starch.
We identify starch concentration as the key factor influencing sauce stability,
with direct implications for practical cooking. Specifically, we delineate a regime
where starch concentrations below 1% (relative to cheese mass) lead to the formation
of system-wide clumps, a condition determining what we term the “Mozzarella Phase”
and corresponding to an unpleasant and separated sauce. Additionally, we examine
the impact of cheese concentration relative to water at a fixed starch level,
observing a lower critical solution temperature that we theoretically rationalized
by means of a minimal effective free-energy model. We further analyze the effect
of a less traditional stabilizer, trisodium citrate, and observe a sharp transition
from the Mozzarella Phase to a completely smooth and stable sauce, in contrast
to starch-stabilized mixtures, where the transition is more gradual. Finally,
we present a scientifically optimized recipe based on our findings, enabling a
consistently flawless execution of this classic dish.
acknowledgement: he authors thank Frank Jülicher, for supporting the initiative and
stimulating discussions. We thank Tetsuya Spippayashi for enlightening clarifications
on the historical origins of Cacio e pepe and Giuseppe Ricchitelli for helping with
the construction of the experimental apparatus. We further thank Martina Gaiba,
Alessandro Gaiba, John D. Treado, Virginia Lepore, Eleonora Nanu, Julia Kirsch,
Lara Koehler, Burak Budanur, Irina Pi-Jaumà, Elizabeth Brückner, M.J. Franco Oñate,
Giorgio Nicoletti, and Marco Salvalaglio for their support and for eating up the
sample leftovers. Finally, we thank Simone Frau for taking the photograph in Fig.
1(a).
article_number: '044122'
article_processing_charge: Yes (in subscription journal)
article_type: original
arxiv: 1
author:
- first_name: G.
full_name: Bartolucci, G.
last_name: Bartolucci
- first_name: D. M.
full_name: Busiello, D. M.
last_name: Busiello
- first_name: M.
full_name: Ciarchi, M.
last_name: Ciarchi
- first_name: A.
full_name: Corticelli, A.
last_name: Corticelli
- first_name: I.
full_name: Di Terlizzi, I.
last_name: Di Terlizzi
- first_name: Fabrizio
full_name: Olmeda, Fabrizio
id: 69dbf5fb-8a76-11ed-866b-fb486d8b5689
last_name: Olmeda
- first_name: D.
full_name: Revignas, D.
last_name: Revignas
- first_name: V. M.
full_name: Schimmenti, V. M.
last_name: Schimmenti
citation:
ama: Bartolucci G, Busiello DM, Ciarchi M, et al. Phase behavior of Cacio e Pepe
sauce. Physics of Fluids. 2025;37(4). doi:10.1063/5.0255841
apa: Bartolucci, G., Busiello, D. M., Ciarchi, M., Corticelli, A., Di Terlizzi,
I., Olmeda, F., … Schimmenti, V. M. (2025). Phase behavior of Cacio e Pepe sauce.
Physics of Fluids. AIP Publishing. https://doi.org/10.1063/5.0255841
chicago: Bartolucci, G., D. M. Busiello, M. Ciarchi, A. Corticelli, I. Di Terlizzi,
Fabrizio Olmeda, D. Revignas, and V. M. Schimmenti. “Phase Behavior of Cacio e
Pepe Sauce.” Physics of Fluids. AIP Publishing, 2025. https://doi.org/10.1063/5.0255841.
ieee: G. Bartolucci et al., “Phase behavior of Cacio e Pepe sauce,” Physics
of Fluids, vol. 37, no. 4. AIP Publishing, 2025.
ista: Bartolucci G, Busiello DM, Ciarchi M, Corticelli A, Di Terlizzi I, Olmeda
F, Revignas D, Schimmenti VM. 2025. Phase behavior of Cacio e Pepe sauce. Physics
of Fluids. 37(4), 044122.
mla: Bartolucci, G., et al. “Phase Behavior of Cacio e Pepe Sauce.” Physics of
Fluids, vol. 37, no. 4, 044122, AIP Publishing, 2025, doi:10.1063/5.0255841.
short: G. Bartolucci, D.M. Busiello, M. Ciarchi, A. Corticelli, I. Di Terlizzi,
F. Olmeda, D. Revignas, V.M. Schimmenti, Physics of Fluids 37 (2025).
date_created: 2025-05-11T22:02:40Z
date_published: 2025-04-01T00:00:00Z
date_updated: 2026-04-28T13:24:53Z
day: '01'
ddc:
- '530'
department:
- _id: EdHa
doi: 10.1063/5.0255841
external_id:
arxiv:
- '2501.00536'
isi:
- '001482986200001'
file:
- access_level: open_access
checksum: 242d05898aa0a2348b9c108747adb5ce
content_type: application/pdf
creator: dernst
date_created: 2025-05-12T09:31:22Z
date_updated: 2025-05-12T09:31:22Z
file_id: '19681'
file_name: 2025_PhysicsFluids_Bartolucci.pdf
file_size: 4926853
relation: main_file
success: 1
file_date_updated: 2025-05-12T09:31:22Z
has_accepted_license: '1'
intvolume: ' 37'
isi: 1
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
publication: Physics of Fluids
publication_identifier:
eissn:
- 1089-7666
issn:
- 1070-6631
publication_status: published
publisher: AIP Publishing
quality_controlled: '1'
related_material:
link:
- description: News on ISTA
relation: press_release
url: https://ista.ac.at/en/news/2025-ig-nobel-prize-for-perfect-pasta-sauce/
scopus_import: '1'
status: public
title: Phase behavior of Cacio e Pepe sauce
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: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 37
year: '2025'
...
---
_id: '17892'
abstract:
- lang: eng
text: "Enzyme-substrate kinetics form the basis of many biomolecular processes.
The interplay between substrate binding and substrate geometry can give rise to
long-range interactions between enzyme binding events. Here we study a general
model of enzyme-substrate kinetics with restricted long-range interactions described
by an exponent −\U0001D6FE. We employ a coherent-state path integral and renormalization
group approach to calculate the first moment and two-point correlation function
of the enzyme-binding profile. We show that starting from an empty substrate the
average occupancy follows a power law with an exponent 1/(1−\U0001D6FE) over time.
The correlation function decays algebraically with two distinct spatial regimes
characterized by exponents −\U0001D6FE on short distances and −(2/3)(2−\U0001D6FE)
on long distances. The crossover between both regimes scales inversely with the
average substrate occupancy. Our work allows associating experimental measurements
of bound enzyme locations with their binding kinetics and the spatial conformation
of the substrate."
acknowledgement: We thank F. Piazza, M. Henkel, and F. Jülicher for helpful feedback
and the entire Rulands group for fruitful discussions. We thank W. Reik, S. Clark,
T. Lohoff, and I. Kafetzopoulos for fruitful discussions about the biological aspects
of this work. This project has received funding from the European Research Council
(ERC) under the European Union's Horizon 2020 research and innovation program (Grant
No. 950349). This project has received funding from the European Union's Horizon
2020 research and innovation programme under the Marie Skłodowska-Curie Grant No.
101034413.
article_number: '024404'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Fabrizio
full_name: Olmeda, Fabrizio
id: 69dbf5fb-8a76-11ed-866b-fb486d8b5689
last_name: Olmeda
- first_name: Steffen
full_name: Rulands, Steffen
last_name: Rulands
citation:
ama: Olmeda F, Rulands S. Field theory of enzyme-substrate systems with restricted
long-range interactions. Physical Review E. 2024;110(2). doi:10.1103/PhysRevE.110.024404
apa: Olmeda, F., & Rulands, S. (2024). Field theory of enzyme-substrate systems
with restricted long-range interactions. Physical Review E. American Physical
Society. https://doi.org/10.1103/PhysRevE.110.024404
chicago: Olmeda, Fabrizio, and Steffen Rulands. “Field Theory of Enzyme-Substrate
Systems with Restricted Long-Range Interactions.” Physical Review E. American
Physical Society, 2024. https://doi.org/10.1103/PhysRevE.110.024404.
ieee: F. Olmeda and S. Rulands, “Field theory of enzyme-substrate systems with restricted
long-range interactions,” Physical Review E, vol. 110, no. 2. American
Physical Society, 2024.
ista: Olmeda F, Rulands S. 2024. Field theory of enzyme-substrate systems with restricted
long-range interactions. Physical Review E. 110(2), 024404.
mla: Olmeda, Fabrizio, and Steffen Rulands. “Field Theory of Enzyme-Substrate Systems
with Restricted Long-Range Interactions.” Physical Review E, vol. 110,
no. 2, 024404, American Physical Society, 2024, doi:10.1103/PhysRevE.110.024404.
short: F. Olmeda, S. Rulands, Physical Review E 110 (2024).
corr_author: '1'
date_created: 2024-09-08T22:01:12Z
date_published: 2024-08-01T00:00:00Z
date_updated: 2025-09-08T09:17:18Z
day: '01'
ddc:
- '530'
department:
- _id: EdHa
doi: 10.1103/PhysRevE.110.024404
ec_funded: 1
external_id:
isi:
- '001299670100004'
pmid:
- '39294986'
file:
- access_level: open_access
checksum: 67fc2cc8eee3155e5c3b7380307d8284
content_type: application/pdf
creator: dernst
date_created: 2024-09-11T05:59:36Z
date_updated: 2024-09-11T05:59:36Z
file_id: '18053'
file_name: 2024_PhysReviewE_Olmeda.pdf
file_size: 445696
relation: main_file
success: 1
file_date_updated: 2024-09-11T05:59:36Z
has_accepted_license: '1'
intvolume: ' 110'
isi: 1
issue: '2'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: fc2ed2f7-9c52-11eb-aca3-c01059dda49c
call_identifier: H2020
grant_number: '101034413'
name: 'IST-BRIDGE: International postdoctoral program'
publication: Physical Review E
publication_identifier:
eissn:
- 2470-0053
issn:
- 2470-0045
publication_status: published
publisher: American Physical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: Field theory of enzyme-substrate systems with restricted long-range interactions
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 110
year: '2024'
...