Alexander Hanzl

New preprint on technologies to scale up CRISPR screens.

We use them to map 665,856 pairwise genetic perturbations and outline a path to comprehensive interaction mapping in human cells.

We also introduce an approach for cloning lentiviral libraries with billions of elements.

We introduce #ProxiCapture, an affinity-proteomics platform to map degrader-induced interactions in native cell & tissue lysates. We uncover a context-dependent “glueable” proteome and a scalable route to accelerate molecular glue discovery 🤗
@ibc2-gu.bsky.social @goetheuni.bsky.social

New research group leader for functional genomics Molecular biologist Matthias Muhar becomes part of the MPI-CBG faculty

New research group leader @matthiasmuhar.bsky.social joins @mpi-cbg.de! 🥳 With his group "Functional genomics of proteome remodeling,” Matthias wants to pursue high-throughput genetic studies to understand how protein turnover is regulated. Welcome, Matthias! www.mpi-cbg.de/news-outreac...

TF-MAPS: fast high-resolution functional and allosteric mapping of DNA-binding proteins Transcription factors (TFs) bind specific DNA sequences to control gene expression. Modulating TF activity is of considerable therapeutic interest but very few TFs have been successfully drugged. TF D...

TF-MAPS: fast high-resolution functional and allosteric mapping of DNA-binding proteins by @XianghuaLi2

Are Transcription Factors really 'undruggable'?

www.biorxiv.org/content/10.1...

Mapping the diverse topologies of protein-protein interaction fitness landscapes De novo binder discovery is unpredictable and inefficient due to a lack of quantitative understanding of protein-protein interaction (PPI) sequence-function landscapes. Here, we use our PANCS-Binder t...

Our latest work seeks to answer a longstanding question: why is discovering new protein binders seemingly unpredictable – and can we better quantify and understand the de novo binder discover process? 1/12

www.biorxiv.org/content/10.1...

Just out in @science.org: Together with the lab of @wilhelmpalm.bsky.social, we used sequential in-vitro/in-vivo CRISPR screens to decipher metabolic adaptations in tumors. We find that acidosis is a dominant factor that shapes energy metabolism and stress resilience. www.science.org/doi/10.1126/...

Really excited to share our latest work led by @mattiaubertini.bsky.social and @nesslfy.bsky.social: we report that cohesin loop extrusion creates rare but long-lived encounters between genomic sequences which underlie efficient enhancer-promoter communication.
www.biorxiv.org/content/10.1...
A🧵👇

🚨 We're hiring, please share! The FMI seeks a tenure-track Group Leader (Assistant Prof) in Structural Biology 🔬
Innovative scientists in genome regulation, RNA metabolism, or protein homeostasis—especially using cutting-edge approaches—apply now at www.fmi.ch/education-ca...

Image of Toronto

JOB ALERT 🚨 We are hiring TWO principal investigators in cell, molecular, systems, or chemical biology in Toronto, Canada at @sinaihealth.bsky.social. We provide a generous startup, fully funded salary and academic appointment at U of Toronto.

www.nature.com/naturecareer...

Please repost!

The genetic architecture of the human bZIP family Generative biology holds the promise to transform our ability to design and understand living systems by creating novel proteins, pathways, and organisms with tailored functions that address challenge...

I am happy to finally share this preprint of my PhD project in @guillaumediss.bsky.social lab at the FMI in Basel.
We used ddPCA to map the genetic architecture of the entire human bZIP interaction network.

www.biorxiv.org/content/10.1...

Thanks to all our co-authors for the great collaboration!

SNAP-tag2 for faster and brighter protein labeling - Nature Chemical Biology SNAP-tag is a widespread tool for labeling protein for bioimaging. Now, Kühn et al. report SNAP-tag2 with increased labeling kinetics and brightness, which translates into a better performance in live...

Finally out in Nature Chem Bio:
SNAP-tag2 for faster and brighter protein labeling
www.nature.com/articles/s41...
Thank you Steffi and Veselin.

ChAHP Silences SINE Retrotransposons by Inhibiting TFIIIB Recruitment Short interspersed nuclear elements (SINEs) are abundant non-autonomous transposable elements derived from RNA polymerase III (POL III)-transcribed short non-coding RNAs. SINEs retain sequence feature...

📖 Happy to share our recent preprint! www.biorxiv.org/content/10.1... We discovered how SINEs are kept silent: the ChAHP protein complex acts as a molecular brake on POL III transcription retrotransposons. A 🧵:

Novel insights into the silencing of an understudied transposable element - check out our latest preprint by @jakobschnabl.bsky.social and colleagues

Primed for degradation: How weak protein interactions enable molecular glue degraders Molecular glues are small drug-like molecules that induce de novo protein–protein interactions or facilitate pre-existing weak interactions between pr…

📝 🚨 Review alert from the Thomä Lab

@alexanderhanzl.bsky.social, Stefan and Clara collected their thoughts on recent molecular glue degrader modalities. Packed with computational predictions, mutations mimicking glues, bivalent engagement and a discussion on mode of action.
tinyurl.com/mpmbuuky

Huge hanks to @labthoma.bsky.social, @fmiscience.bsky.social and @snsf-ch.bsky.social for all the support

tinyurl.com/mpmbuuky

- Mutations mimicking glues by @brianliau.bsky.social al and Ning Zheng
- Covalent and bivalent glue engagement by @dannomura.bsky.social, Nathanael Gray, @georgwinter.bsky.social and @alessiociulli.bsky.social
- And finish it of with a discussion on general mode-of-action.

We highlight among others:
- Computational predictions of neosubstrates by @monterosatx.com
- Engineering target specificity by @ericfischer.bsky.social, colleagues @novartis.bsky.social as well as David Liu

📝 Review alert 🚨 from @labthoma.bsky.social
Stefan, Clara, Nico and I have collected our thoughts on recent discoveries of molecular glue degraders for a special issue of CurrOpinStrucBiol edited by Philip Biggin and Roderick Hubbard. 👇

tinyurl.com/mpmbuuky

Come and join us! We’re hiring a new Group Leader in Generative Biology at the @sangerinstitute.bsky.social

Building AI models or the data to train them?

Core funding of >$130M a year for a faculty of ~30.

www.nature.com/naturecareer...

acrobat.adobe.com/id/urn:aaid:...

pls RT!

Him: Structures in PDB format Her: Do you mean mmCIF and not deprecated format, right? Him: Her: RIGHT?

Changes in PDB IDs are coming that will require use of PDBx/mmCIF file format... will you be ready? #MayThe4th
Resources are available to help: www.wwpdb.org/docume...

Celebrating 10 years of our lab with a new preprint:
www.biorxiv.org/content/10.1...
How does enhancer location within a TAD control transcriptional bursts from a cognate promoter?
Experiments by Jana Tünnermann and modelling by Gregory Roth

Something that qualifies as big news from my side:
I am very happy and excited to announce that I have been appointed as Life Science Director at AITHYRA, a new Research Institute for Biomedical Artificial Intelligence.

Find out more in the link and 🧵 below

lnkd.in/d_HaGuSE

A comprehensive Schizosaccharomyces pombe atlas of physical transcription factor interactions with proteins and chromatin Transcription factors (TFs) are key regulators of gene expression, yet many of their targets and modes of action remain unknown. In Schizosaccharomyce…

The realignment of research in our group @fmiscience.bsky.social is beginning to bear fruit. Proud of our captain @merleskribbe.bsky.social and the whole team!
www.sciencedirect.com/science/arti...

We are hiring two tenured full-time professors in Salzburg, Austria!

Today in @nature.com we share our back-to-back stories with Ning Zheng’s lab revealing chemical-genetic convergence between a molecular glue degrader & E3 ligase cancer mutations. 1/5

C-terminal amides mark proteins for degradation via SCF–FBXO31 - Nature SCF–FBXO31 scans proteins for C-terminal amidation and marks them for subsequent proteasomal degradation.

🎉Super excited to share our story on how the substrate receptor FBXO31 functions as a quality control factor by recognizing amides. This has been an amazing collaboration between Bode lab and @jcornlab.bsky.social. Special shutout goes to @matthiasmuhar.bsky.social www.nature.com/articles/s41...

📣 Please share: We’re hiring a tenure-track Group Leader in Multicellular Systems to explore the molecular and cellular mechanisms driving the formation, maintenance, or destabilization of tissues, organs and organisms. Apply at: www.fmi.ch/education-ca...

Permanent position for a Linux Systems Engineer: Are you fond of scientific computing and/Linux/HPC and would enjoy working in a vibrant research environment? Have a look at our job opening: www.fmi.ch/education-ca...