Johannes Zuber
@johanneszuber.bsky.social
1.2K followers 980 following 10 posts
Senior Group Leader IMP / Adjunct Professor Medical University of Vienna. Fascinated by functional genetics (CRISPR, RNAi, degrons) and time-resolved omics towards understanding cancer biology and probing new therapeutic concepts.
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johanneszuber.bsky.social
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/...
johanneszuber.bsky.social
Thus, acidosis is not merely a byproduct of altered metabolism in tumors. Rather, it is a dominant factor in the tumor microenvironment that orchestrates a boost in mitochondrial energy production, thereby rendering cancer cells resilient to different types of stress.
johanneszuber.bsky.social
Acidosis induces mitochondrial fusion by abrogating Ras-induced mitochondrial fragmentation. Intriguingly, acidosis triggers this effect by inactivating cytoplasmic ERK1/2 and, in turn, the fission factor DRP1, revealing a direct link between oncogenic RAS signaling and energy metabolism.
johanneszuber.bsky.social
…and goes along with increased mitochondrial activity and a switch from glycolysis to oxidative mitochondrial metabolism, leading to a boost in ATP production that renders cancer cells resilient to diverse stresses.
johanneszuber.bsky.social
Acidosis triggers profound changes in the shape and architecture of mitochondria, which reorganize from fragmented organelles into fused tubular networks. Mitochondrial fusion is required for cell proliferation and survival under acidosis…
johanneszuber.bsky.social
In subsequent stress combination screens and follow-up studies, we find that acidosis overwrites the effects of many other stresses such as shortages in nutrients or growth factors. For example, merely lowering the media pH enables glucose-starved cancer cells to re-enter proliferation!
johanneszuber.bsky.social
Through genome-wide CRISPR screens, we characterized fitness genes under diverse metabolic stresses and sequentially screened 771 stress-specific fitness genes in pancreatic tumors in vivo. Gene dependency profiles in vivo closely mimicked only one stress condition in cell culture: Acidosis!
johanneszuber.bsky.social
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/...
Reposted by Johannes Zuber
impvienna.bsky.social
📢Open call: the International Birnstiel Award for Doctoral Research in Molecular Life Sciences is now accepting nominations!

Do you know an outstanding PhD student who deserves recognition?

Nominate them by 30 June 👉 www.imp.ac.at/achievements...

🎥 www.youtube.com/watch?v=ghfQ...
International Birnstiel Award for Doctoral Research in Molecular Life Sciences
YouTube video by Research Institute of Molecular Pathology
www.youtube.com
Reposted by Johannes Zuber
impvienna.bsky.social
Here's a first collection of great life science institutes worldwide you can follow to help you get back in the loop. 🌍🔬

Did we miss any? Let us know, and we'll add them!

go.bsky.app/A5Jrf8N
johanneszuber.bsky.social
Are you a #Masters student interested in translational
#cancer research, tumor immunology and #CRISPR screens? Then apply to our lab at the @impvienna.bsky.social in Vienna:

www.imp.ac.at/career/open-...

#oncology, #cancerresearch, #CRISPR
johanneszuber.bsky.social
Another masterpiece from our friends in the Obenauf lab, deciphering an entire cascade that enables cancer cells to evade immunity & discovering a key role of monocytes in T-cell activation! Huge congrats to @obenaufa.bsky.social, @aelewaut.bsky.social, @guillemxtivill.bsky.social & all co-authors!
obenaufa.bsky.social
1/23 Big news for the #ObenaufLab! So excited to finally share our new study providing another puzzle piece, why immunotherapy fails in many tumors, now out in @Nature 🧵👇 www.nature.com/articles/s41...
Reposted by Johannes Zuber
impvienna.bsky.social
Are you a #postdoc with an innovative vision for starting your own lab in #Syntheticbiology, #Genomics, #GeneRegulation, #Development, #Cancer, #Immunology or #InfectionBiology?

@IMPvienna is inviting applications for group leader positions: www.imp.ac.at/career/open-...

Pls share!