Miloš Tišma

biorxiv.orgChromosome topology gates productive RecA homology searchIn homologous recombination, DNA repair depends on recombinase filaments finding homologous templates on chromosomes whose topology is continually remodeled by replication and transcription. How dynam...

I just still cannot help myself from looking that these beautiful real-time dynamics videos from @anjbadri.bsky.social lab! thanks to all the authors from @joeloparo.bsky.social / @anjbadri.bsky.social and TJ Ha labs.

Miloš Tišma@tismaa.bsky.social

I'm happy to share the first paper from my postdoc work: www.biorxiv.org/content/10.6... How does RecA find one homologous sequence in an entire chromosome -and what turns that encounter into a repair-competent one? We find that DNA topology is the gatekeeper !! 1/10

But this faster search was completely unproductive: we observed 0/100 homology-resolution events over 2 h !!! Drug washout restored normal dynamics and resolution. Mobility can solve the encounter problem; DNA topology solves the commitment problem. 9/10

Our model is that RecA explores the chromosome through filament movement and extension, while local negative supercoiling enables productive strand engagement and stabilization. Chromosome topology is therefore an active regulator of homology search - not passive DNA packaging !! 10/10

This topological preference was broadly conserved in bacteria! RecA orthologs from E. coli, Caulobacter, Bacillus, Streptomyces, and Staphylococcus all strongly favored negatively supercoiled targets, despite their evolutionary and chromosomal diversity. 7/10

We then tested the model in living Caulobacter cells. Removing negative supercoiling with novobiocin (blocking the gyrase) did not prevent RecA filament formation or pole-to-pole search. Instead, filaments traversed the cells ~45% faster and paused less. 8/10

This was not simply an effect of DNA compaction. Binding was essentially unchanged from highly compacted targets to DNA stretched beyond 90% of its contour length. Artificially compacting relaxed DNA with PEG also failed to rescue binding. Topology-not compaction-was key. 5/10

Real-time imaging revealed the step controlled by topology: commitment. Transient sampling occurred on both DNA states, but we saw no transient-to-stable transitions on relaxed targets. On supercoiled DNA, stable capture also pinned a plectoneme at the homologous site. 6/10

The central result: negative supercoiling acts as a selectivity filter. RecA filaments can sample both relaxed and supercoiled DNA, but they efficiently commit to stable homologous capture only on negatively supercoiled targets. 3/10

The effect was striking. Within 15 min, 85/85 negatively supercoiled DNA molecules were stably bound, versus 5/543 relaxed molecules. Even after 1 h, <3% of relaxed targets bound. The kinetic preference for negative supercoiling was ~100-fold. 4/10

We used a single-molecule assay that lets us tune the topology to precise supercoiling levels of DNA targets while watching RecA-ssDNA filaments search and bind in real time. 2/10

20 July

So thankful for winning the Poster Prize at @fusionconf.bsky.social in Prokaryotic Cell Biology for my research on the effects of chromosome topology on DNA repair! Looking forward to developing the work further and sharing more soon !! 🤩🤩

@jovanakaljevic.bsky.social

20 July

I’m grateful for the insightful discussions, feedback, and support from the research community. Congratulations to all the winners!

Miloš Tišma reposted

Jovana Kaljević ⬜️

18 July

Honoured to receive a talk prize at the Fusion Conference on Prokaryotic Cell Biology in Lisbon last week. Thank you to the organisers for a wonderful meeting, and to all the scientists whose ideas continually help me grow! @fusionconf.bsky.social #ProkaryoticCellBio #scienceisbeautiful

24 June

In the last steps of the manuscript writing and I just ran the full document through the new @qedscience.bsky.social "Meet the 1%" manuscript comparison... I am beyond excited to share my postdoc work from @joeloparo.bsky.social lab in the next few weeks! 🤩🤩

pnas.orgVersatile NTP recognition and domain fusions expand the functional repertoire of the ParB-CTPase fold beyond chromosome segregation | PNASNucleotide triphosphate (NTP)-dependent molecular switches regulate essential cellular processes by cycling between active and inactive states thro...

4 Dec 2025

Outstanding work from @jovanakaljevic.bsky.social as together with the team they explore the depths of ParB world🤩 On my list!

Jovana Kaljević ⬜️@jovanakaljevic.bsky.social

Our preprint is now published in PNAS! This came together thanks to a great collaboration with Antoine Hocher and a strong team effort from the Le Lab. Thank you to the reviewers and to everyone who helped improve it. I hope ParB aficionados will enjoy it. www.pnas.org/doi/10.1073/...

Miloš Tišma reposted

Jovana Kaljević ⬜️

@jovanakaljevic.bsky.social

4 Dec 2025

Miloš Tišma reposted

23 Sept 2025

Wow, what an honor! The @biophysicalsoc.bsky.social awards me the esteemed '2026 Kazuhiko Kinosita Award in Single-Molecule Biophysics' 'for groundbreaking contributions to the field of nanobiology and single-molecule biophysics, from nanopores to SMC molecular motors'. Feel honored, very thankful!

8 Aug 2025

Absolutely preposterous size of a Giant Sequoia…

Miloš Tišma reposted

25 June 2025

Here's a new very exciting paper from our #CDlab: www.cell.com/cell-reports... In an exemplary in vitro/in vivo study, 1st authors ‪@btanalikwu.bsky.social‬ & Alice Deshayes showed that dense linear protein arrays (e.g. telomeres) do stop loop-extruding SMCs! Great collaboration with Marcand lab.

@physicsoflifeuk.bsky.social

9 June 2025

Wrapped up a GRC on Bacterial Cell Biology and Development last week in SNHU, New Hampshire. A full week of talks on novel bacterial systems and new mechanistic details on eastablished systems. Great chance to learn, connect with peers and enjoy science!

Miloš Tišma reposted

@physicsoflifeuk

10 Apr 2025

We're excited to host two fantastic speakers at our next online @physicsoflifeuk.bsky.social ECR Seminar on Tuesday 15 April, 2–3 PM BST: Tisma Milos and Thomas McLean chaired by @veronicabiga.bsky.social Please register below for the Zoom link: lnkd.in/dSynrAe8

youtube.comThe Man Who Used Gene Editing On Babies - Jiankui HeYouTube video by BioAcc Podcast

4 Mar 2025

Just watched a podcast with Jiankui He, the first person to go. through with CRISPR editing in human babies in 2018. He started a complex debate (both in productive and destructive ways) on ethics in science, future of gene editing and safety of current methods.   www.youtube.com/watch?v=ch03...

4 Mar 2025

I must say while he mentions ethics and transparency of his results he did have strange requests on X/Twitter: - requested upfront to have his 2018 results published in Science or Nature - continuously has strange financial request to give a talk at a major US university

1 Mar 2025

A lovely visit to Yale School of Medicine to see @leoschaerfen.bsky.social graduate with a spectacular PhD work. 🤩

biorxiv.orgIntracellular competition shapes plasmid population dynamicsConflicts between levels of biological organization are central to evolution, from populations of multicellular organisms to selfish genetic elements in microbes. Plasmids are extrachromosomal, self-r...

25 Feb 2025

Biologist-"Let me order some Biotin-11-dUTP" Chemist-"Let me order some ((2R,3S,5R)-5-(2,4-dioxo-5-(3-(6-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)hexanamido)prop-1-yn-1-yl)-3,4-dihydropyrimidin-1(2H)-yl)-3-hydroxytetrahydrofuran-2-yl)methyl hydrogen triphosphate" 😅

Miloš Tišma reposted

Michael Baym

@baym.lol

21 Feb 2025

Legitmately thrilled to share our latest work, in which @fernpizza.bsky.social solved an experimental challenge in plasmid biology as old as the field: measuring how plasmids compete and evolve within individual cells!

Fernando Rossine@fernpizza.bsky.social

I'm so happy that I can finally share the results of my first postdoc paper with @baym.lol!!! Turns out plasmids are an amazing system to study multi-scale evolution and we can track within-cell and between-cell dynamics! (1/n) www.biorxiv.org/content/earl...

science.orgScientists rally in support of Serbia’s anticorruption protestsBut some criticize “weak and formal” support for protests from scientific institutions

13 Feb 2025

Nice to see that Science(.org) supports and spreads awareness of the massive protests currently ongoing in Serbia! Peaceful protests lead by Serbian University students (later joined by many others), have gathered more than 200 000 people on occasions! www.science.org/content/arti...

13 Feb 2025

These protests are unique in their nature as they are: - entirely apolitical - peaceful - lead by students, and no single party or individual leading them - they have reignited hope, kindness and huge support in a country of wilted spirit due to corrupt government in the past couple of years

30 Jan 2025

This is so real 🤣🤣 I do not know the explanation of this but definitely resonates very well…

Miloš Tišma reposted

Rosana Collepardo

@rcollepardo.bsky.social

23 Jan 2025

What is the multiscale structure of chromatin condensates? How does it shape thermodynamic and material properties? We address this at near-atomistic resolution🔥🔥🔥 using cryoET (Rosen & Villa labs, led by H Zhou), a new multiscale model (K Russell) and cryoET-guided sims (J Huertas & J Maristany)

Jan Huertas@janhuemar.bsky.social

Exciting new preprint alert! 🚨 The Collepardo lab, teaming up with Huabin Zhou and the Rosen lab we took a deep, high-resolution look into chromatin condensates! [1/6] #Chromatin #MD @rcollepardo.bsky.social @juliamaristany.bsky.social www.biorxiv.org/content/10.1...

biorxiv.orgbiorxiv.org

Miloš Tišma reposted

@joostsnijder.bsky.social

23 Jan 2025

Congrats to #CDlab graduate ‪Miloš Tišma for winning a Rubicon grant to pursue postdoc research on antibiotic resistance at Harvard Medical School!

Miloš Tišma@tismaa.bsky.social

Glad to receive the trust and recognition in being awarded a Dutch NWO Rubicon Fellowship for important work on antibiotic resistance. I will be tackling this problem using a combination of biophysics, biochemistry and microbiology in Joe Loparo lab at Harvard Medical School (Dept. of BCMP).

Thanks to all that helped me with the ideation, application, and editing!

Miloš Tišma reposted

Joost Snijder

19 Dec 2024

About the price of a hefty GPU workstation, close to a student’s annual consumables cost in the lab, attendence to 5 conferences, full week of Krios data collection, cost of ~100 samples for proteomics data collection… so many things to better spend the money than these outrageous publishing fees.

Cees Dekker@ceesdekker.bsky.social

oefff, paying 11253 euro as open access fee for publishing a single paper in Cell (@cp-cell.bsky.social) - that's an outrageous amount of money.

Miloš Tišma reposted

Michael Eisen

@mbeisen.bsky.social

15 Dec 2024

The truth is nobody should care how many protein coding genes there are. The gene is a useful abstraction that loses its utility when defined precisely enough to count.

Veera Rajagopal@doctorveera.bsky.social

Exactly how many protein-coding genes are there in the human genome? The truth is no one knows. The numbers change based on what database you use as reference.

Miloš Tišma reposted

This will be me in a few months when i come back @btanalikwu.bsky.social and Jaco 🤣🙈

Oded Rechavi@odedrechavi.bsky.social

Revisiting the lab where you did your post doc and meeting your bench mates who're still there

doi.orgRaising a glass to the Four Friends Doing Science journal clubFour researchers who left Serbia to pursue their careers rely on this group to keep in touch and to navigate life in science.

28 Nov 2024

I hope this can inspire and motivate someone that distances that are often expected to happen as you walk your path through science, do not have to be harmful to your relationships and friendships ☺️

Miloš Tišma@tismaa.bsky.social

Nice to be featured in @natureportfolio.bsky.social Career Column for our personal story on how we kept in touch over the years. From undergrad -> MSc -> PhDs and beyond We added science to our friendships and in turn our friendships to our science! doi: doi.org/10.1038/d415...

doi.orgRaising a glass to the Four Friends Doing Science journal clubFour researchers who left Serbia to pursue their careers rely on this group to keep in touch and to navigate life in science.

28 Nov 2024

28 Nov 2024

Many thanks to the lovely editors and production for the quick process! 🙏

27 Nov 2024

Out today in Nucleic Acids Research! My final publication from @ceesdekker.bsky.social lab together with A.M. Gonzalez ! Together with @gruberlab.bsky.social in Lausanne, we show the interaction between supercoiled DNA and partitioning protein ParB. Read full: doi.org/10.1093/nar/...

Miloš Tišma reposted

27 Nov 2024

Latest #CDlab paper in Nucleic Acid Research: academic.oup.com/nar/article/... Great work by Alejandro Martin-Gonzalez, @tismaa.bsky.social ea collaboring with @gruberlab.bsky.social, showing the interplay of DNA supercoiling & ParB condensation, 2 processes that set bacterial genome organization.

who.intWorld Antimicrobial Awareness Week 2024World Antimicrobial Awareness Week aims to increase awareness of global antimicrobial resistance (AMR) and to encourage best practices.

AMR awareness week ends today, but still something to keep in mind always! www.who.int/campaigns/wo...

Specifically, antibiotics have been such an incredible contributor to human health since their discovery nearly ~100 years ago by A. Fleming. It's scary to think that we could be slowly reverting to the times where you could die from the most meaningless open-cut or routine medical procedure.

I hope to see more responsible use of antibiotics, responsible prescription of antibiotics, and novel development of both antibiotics and antibiotic alternatives in the future!

The migration of scientists and researchers en masse to this platform is great! Time to pick up my time here a bit🤩