Judith Kribelbauer

Now that I'm settled in at @umasschan.bsky.social, I'm hiring at all levels: grad students, post-docs, and software engineers/bioinformaticians!

The goal of my lab is to understand the regulatory role of every nucleotide in our genomes and how this changes across every cell in our bodies.

While over here discussions are about slashing Science funding, the Swiss are proposing to put it center stage on their currency. And I thought I was returning to the "Mecca of Science", not leaving it... 😅 Also, is this even real money? www.neuebanknotenserie.ch/detailview.h...

Beautifully controlled system to delineate primary from context-specific TF binding, revealing how chromatin state shapes TF binding specificity during differentiation and vice versa!

Excited to see that our study on context-specific transcription factors was named as one of 8 remarkable outputs of 2024 by the Swiss Institute of Bioinformatics.

The Range Extender
For enhancers to function
At long distances

#ChromatinHaiku

Congrats!

same here. Have an 18-month-old and the only time I get anything done is at night when he sleeps 🫠 You are not alone, hang in there!

Agree, there are definitely cases where syntax is important, the question is more how to model it well when it isn't. I would think the latter is important for accuracy, which is where models tend to start underperforming (e.g. predicting activity for personalised genomes). I like your suggestion!

might be time to reconsider how we train machine learning models. Almost every model I come across uses convolutional filters that attempt to learn syntax, when perhaps none is present...

Really cool work using a gene synteny-based strategy to identify enhancer conservation across species w/o seq similarity. Last figure is my favorite: while TFBS content is conserved, TFBS syntax is not! Aligns with our findings on TF cooperativity, where a specific syntax was not required.

Baby Is Healed With World’s First Personalized Gene-Editing Treatment

As a scientist and mom of a little boy this story really touched me. The rewards of science funding go way beyond $ return on investment (& NIH's ROI is unparalleled). Hats off to the parents making this incredibly tough decision, paving the way for future treatments. www.nytimes.com/2025/05/15/h...

Home - Kribelbauer Lab USC Dornsife

How is it end of April already? Excited to share that the Kribelbauer Lab is up and running @USC/MCB. Grateful for my first two PhD students @m-finegan.bsky.social @christinagirgis.bsky.social. We are dev scalable, genome-int. tools to study TF & enhancer regulation. Website now live bit.ly/4jo8Tjg

MPRAbase (mprabase.ucsf.edu) , a customized database for massively parallel reporter assays (MPRAs) to easily find and download MPRA data. Amazing work by Jingjing Zhao, Fotis Baltoumas, Georgios Pavlopoulos, @vagar.bsky.social, ilias Georgakopoulos-Soares & others.

genome.cshlp.org/content/earl...

The End of Disease

100% agree w Lowe on this: "But how is AGI going to suddenly reveal what is now hidden? The sum total of all the medical information in the world right now is not enough. And it's going to go on being Not Enough for quite some time..." Let's also focus on Exp. Tools! www.science.org/content/blog...

Postdoctoral Scholar in Genomics University of California, Merced is hiring. Apply now!

Looking for a Postdoc position in #Genomics at the interface of computational and molecular biology? -> The Rube lab at UC Merced is recruiting. I highly recommend you reach out! aprecruit.ucmerced.edu/JPF01874

Thank you! Very complementary to the synthetic platform your lab built. Still challenging to go beyond 5kb for us, so tackling distal enhancer regulation will take a lot more engineering! Looking forward to future work from your lab!

Scalability is definitely the next big step in the journey. Also in the works a universal replacement cassette. With the current throughput it can still be useful for benchmarking/providing insights into potential shortcoming of "AI" tools.

Thank you!

Thank you! Been a long time coming...

Looking forward to feedback from the community. We want to move into new applications (SynBio, genAI, ...), reach out if interested!

Stay tuned, we have some exciting collaborations in the works (@lucapinello.bsky.social lab), applying EXTRA-seq to test cell type specificity & the dynamic range of synthetically created sequences.

We evaluated combinatorial E-P modifications, finding a new role for the TATA box, which acts as a 'noise suppressor' to prevent expression from weak (1 TFBS) "enhancers". With increasing E strength it switches to activation thus expanding the dynamic range.

It also allows testing "out-of context" enhancer activities and what enhancer-native molecular features correlate with expression.

We sys compare it to plasmid-based MPRAs and deep learning models (Enformer @DeepMind), finding new bio insights & suggesting ways to improve predictions.
We resolve expression differences down to distinct TF configurations on DNA, highlighting shortcomings of MPRAs and DL tools.

EXTRA-seq can be targeted to endogenous loci, allowing us to measure "near-native" gene expression as a function of dozens of newly introduced E-P genotypes (over 2kb apart).

EXTRA-seq: a genome-integrated extended massively parallel reporter assay to quantify enhancer-promoter communication Precise control of gene expression is essential for cellular function, but the mechanisms by which enhancers communicate with promoters to coordinate this process are not fully understood. While seque...

Finally out! We present EXTRA-seq, a new EXTended Reporter Assay to quantify endogenous enhancer-promoter communication at kb scale!
www.biorxiv.org/content/10.1...
A 🧵about what it can do:
#SynBio #DeepLearning #GeneRegulation

Neat study introducing a new system to study enhancer cooperativity across large distances in endogenous (!) contexts - showing that there is still much to learn about E-E and E-P communication. Enhancer order, distance, and strength, & CTCF sites all matter, and in a context-specific manner!

and here the flagship manuscript #Codebook

Curious to learn more about the Codebook Project? years-long, multi-center effort to identify binding specificities for poorly characterized human TFs. Read below if you want to learn more about 'dark' TFs (1/5 preprints in total).

(1/12) Excited to present the results of the large-scale benchmarking of DNA motif discovery tools using the Codebook data compendium on poorly studied human transcription factors and the Codebook Motif Explorer: dx.doi.org/10.1101/2024..., mex.autosome.org ⬇️.