Our evil ORFeome paper is out! In collaboration with @alex-stark.bsky.social, we screened ~4,000 viral proteins and secreted effectors from bacteria and parasites, covering hundreds of diverse pathogens, for phenotypes in human cells.

Last Discovery Seminar before the summer break: On Friday, July 3, Prof. Alexander Stark from the Research Institute of Molecular Pathology @impvienna.bsky.social will talk about “Decoding Transcription Regulation.” Everyone is welcome!

Activator-promoter compatibility in mammals - Hcfc1 is a key and intrinsically CGI-promoter-specific co-activator that cannot activate non-CGI promoters. Lead by @nemcko.bsky.social & Kevin Sabath in collab. with @plaschkalab.bsky.social @impvienna.bsky.social www.biorxiv.org/content/10.6... (1/2)

Activator-promoter compatibility in mammals: a CpG-Island-specific co-activator directly bridges transcription factors to TFIID

Transcription from CpG island (CGI) promoters controls the expression of two-thirds of mammalian genes, yet despite their prevalence, it remains unknown whether CGI-specific co-activators with intrins...

biorxiv.org

Our preprint "Predictive design of tissue-specific mammalian enhancers that function in vivo in the mouse embryo" is on bioRxiv: www.biorxiv.org/content/10.6... . Amazing collaboration by @shenzhichen1999.bsky.social, Vincent Loubiere (@impvienna.bsky.social,@viennabiocenter.bsky.social),... (1/2)

Predictive design of tissue-specific mammalian enhancers that function in vivo in the mouse embryo

Enhancers control tissue-specific gene expression across metazoans. Although deep learning has enabled enhancer prediction and design in mammalian cell lines and invertebrate systems, it remains uncle...

biorxiv.org

Join @stirlingchurchman.bsky.social, @moffittlab.bsky.social, @saramostafavi.bsky.social, me and all speakers for the 2026 CSHL meeting Systems Biology: Global Regulation of Gene Expression, March 11-14. Abstract deadline January 9! More infos and registration at meetings.cshl.edu/meetings.asp...

Read the full story in our preprint! 👇 biorxiv.org/content/10.6... Excited to share this work with my co-first author Kevin Sabath - a fantastic collaboration between the @alex-stark.bsky.social and @plaschkalab.bsky.social labs! 🤝🧪

Activator-promoter compatibility in mammals: a CpG-Island-specific co-activator directly bridges transcription factors to TFIID

Transcription from CpG island (CGI) promoters controls the expression of two-thirds of mammalian genes, yet despite their prevalence, it remains unknown whether CGI-specific co-activators with intrins...

biorxiv.org

Using Hcfc1 as a model, we show it functions as a molecular bridge: it connects CGI-bound TFs directly to TFIID. This recruitment overcomes a rate-limiting step unique to CGI promoters, enabling transcription initiation. 🧬🌉

Do transcriptional activators work on any promoter? Our data says no. 🙅‍♂️ Despite driving ~2/3 of mammalian genes, CpG island (CGI) promoters have remained a puzzle. We identified >50 activators that are exclusively compatible with this promoter class. 🧬

Activator-promoter compatibility in mammals - Hcfc1 is a key and intrinsically CGI-promoter-specific co-activator that cannot activate non-CGI promoters. Lead by @nemcko.bsky.social & Kevin Sabath in collab. with @plaschkalab.bsky.social @impvienna.bsky.social www.biorxiv.org/content/10.6... (1/2)

Activator-promoter compatibility in mammals: a CpG-Island-specific co-activator directly bridges transcription factors to TFIID

Transcription from CpG island (CGI) promoters controls the expression of two-thirds of mammalian genes, yet despite their prevalence, it remains unknown whether CGI-specific co-activators with intrins...

biorxiv.org

Join @stirlingchurchman.bsky.social, @moffittlab.bsky.social, @saramostafavi.bsky.social, me and all speakers for the 2026 CSHL meeting Systems Biology: Global Regulation of Gene Expression, March 11-14. Abstract deadline January 9! More infos and registration at meetings.cshl.edu/meetings.asp...

Read our new preprint where we uncover a hierarchy in human PIC assembly and establish a quantitative framework that connects factor exchange kinetics to the regulation of Pol II activity in living human cells. doi: doi.org/10.64898/202... By A. Oravecz and our collaborators @molinalab.bsky.social

RNA polymerase II initiation factors show different dynamic behaviour upon induced transcription in live cells

Transcription by RNA polymerase II (Pol II) requires the ordered action of general transcription factors (GTFs) forming the pre-initiation complex (PIC). How these events unfold kinetically remains un...

doi.org

Not that long ago, in vivo mouse enhancer design was a dream. Today, it's a reality! Using transfer deep learning to design de novo synthetic embryonic enhancers active in the heart, limb, and CNS. Great collab with @alex-stark.bsky.social lab! @ucibiosci.bsky.social @impvienna.bsky.social

Alex Stark@alex-stark.bsky.social · 7mo ago

Our preprint "Predictive design of tissue-specific mammalian enhancers that function in vivo in the mouse embryo" is on bioRxiv: www.biorxiv.org/content/10.6... . Amazing collaboration by @shenzhichen1999.bsky.social, Vincent Loubiere (@impvienna.bsky.social,@viennabiocenter.bsky.social),... (1/2)

Our preprint "Predictive design of tissue-specific mammalian enhancers that function in vivo in the mouse embryo" is on bioRxiv: www.biorxiv.org/content/10.6... . Amazing collaboration by @shenzhichen1999.bsky.social, Vincent Loubiere (@impvienna.bsky.social,@viennabiocenter.bsky.social),... (1/2)

Predictive design of tissue-specific mammalian enhancers that function in vivo in the mouse embryo

Enhancers control tissue-specific gene expression across metazoans. Although deep learning has enabled enhancer prediction and design in mammalian cell lines and invertebrate systems, it remains uncle...

biorxiv.org

After a huge amount of work w/ @alex-stark.bsky.social's group, a new version of our Ledidi preprint is now out! In an era of AI-designed proteins, the next leap will be controlling when, where, and how much of these proteins are expressed in living cells. www.biorxiv.org/content/10.1...

Programmatic design and editing of cis-regulatory elements

The development of modern genome editing and DNA synthesis has enabled researchers to edit DNA sequences with high precision but has left unsolved the problem of designing these edits. We introduce Le...

biorxiv.org

Messenger RNA is made in the nucleus before it is exported to the cytoplasm for translation. But how are only correctly made mRNAs chosen and remodeled in the nucleus for export? Our new paper investigates the nuclear events leading to human mRNA export. www.nature.com/articles/s41.... (1/4)

Lastly, I’m excited to join @imbmainz.bsky.social in 2026 to start my own lab. We'll explore new mechanisms in eukaryotic gene expression, leveraging ‘evolutionary play’ to uncover how regulation, repurposing, and hijacking shape RNA biology. tinyurl.com/y4x29ctt Thanks for reading! 20/20

My first @umasschan.bsky.social/@impvienna.bsky.social affiliated paper is up! tomtom-lite is a re-implementation of tomtom targeting the ML age of genomics. Fast annotations ("what is this motif?") and simple large-scale discovery of motifs. Check it out! academic.oup.com/bioinformati...

Tomtom-lite: accelerating Tomtom enables large-scale and real-time motif similarity scoring

AbstractSummary. Pairwise sequence similarity is a core operation in genomic analysis, yet most attention has been given to sequences made up of discrete c

academic.oup.com

Jacob Schreiber@jmschreiber91.bsky.social · last yr.

Last week I shared a preprint on tomtom-lite, a super fast re-implementation of Tomtom for annotating short genomic spans with the motifs they most resemble. Now, there's a convenient command line tool `ttl` that comes with the installation. You can get it with `pip instal memelite`

🎉 Congrats to @aelewaut.bsky.social for winning the 2024 #DenisePBarlowAward! 🎖️ She carried out her PhD thesis in @obenaufa.bsky.social's lab (@impvienna.bsky.social), work published in @nature.com. 📄 Paper: rdcu.be/eQv1f ➡️ About the award: bit.ly/3iFbafP

Looks like the previous link is not working... here's a working link! www.biorxiv.org/content/10.1...

Link to preprint: www.biorxiv.org/content/2025...

This has been an amazing collaborative project that keeps on giving. We now have a new 3x larger eORFeome and we will dive deep into pathogen and host biology. If you are interested in scalable approaches to study effectors and their interactions with the host, get in touch! 8/8

Our new preprint is online! Viruses, bacteria and parasites use effector proteins to evade immunity and rewire host cell pathways. Together with @AlexanderStark8, we wondered if we could systematically map what these effectors, regardless of their origin, do in human cells. 1/8

Major new direction in the lab: hacking human cell biology with pathogen effectors (eORFs) - amazing collaboration with @miketilapia.bsky.social lab. Huge congrats to first authors Tomas & He & all co-authors! Check out the pre-print on @biorxivpreprint.bsky.social www.biorxiv.org/content/10.1...

Systematic Discovery of Pathogen Effector Functions across Human Pathogens and Pathways https://www.biorxiv.org/content/10.1101/2025.11.17.687821v1

Join this year's CSH Asia Systems Biology of Gene Regulation & Genome Editing meeting in beautiful Suzhou, China, Oct 20-24. Let's bring the international communities together! Abstract deadline Sept 19! Infos and registration at csh-asia.org?content/2767. Please repost!

Join this year's CSH Asia Systems Biology of Gene Regulation & Genome Editing meeting in beautiful Suzhou, China, Oct 20-24. Let's bring the international communities together! Abstract deadline Sept 19! Infos and registration at csh-asia.org?content/2767. Please repost!