We have started a project trying to predic the interactions/structures of all yeast protein pairs using an AlphaFold pooling approach. We are making the current dataset open and we welcome collaborations.
www.evocellnet.com/2026/03/mapp...
Thanks Judy!
Finally, thanks to Markus for supporting me on this curiosity-driven excursion into fission yeast physiology and genetics, and a HUGE thanks to @jbahler.bsky.social for support, encouragement and advice to all of us throughout the project!
Ladislav ended up making some nice mbx2 overexpression strains using a golden-gate cloning strategy that helped us answer some questions from the revision. Also big thanks to Saniya Raut who used her magic touch to help make some fresh deletion strains for the revisions.
Great job @bencekover.bsky.social for hard work, creativity and thoughtful analysis and for sticking with the project to the end. Also thanks for a job well done to Celeste and the students who followed up on different aspects of this project including George Long, Justin Kong and Ladislav Seres.
A big thank you to @reviewcommons.org, who found four very helpful reviewers for the paper and were patient with us as we followed up on loose ends. Thanks of course to those reviewers, and to @genetics-gsa.bsky.social #GENETICS journal for accepting the paper!
We found it interesting that in the case of flocculation, the flocculins themselves are not conserved but underlying regulatory logic was conserved, a contrast to regulatory rewiring that exists for other phenotypes pubmed.ncbi.nlm.nih.gov/21164485/
This work helps better characterize MLPs in fission yeast and may reveal some mechanisms for forming MLPs that differ from the budding yeast, although it seems like the link between the srb10, srb11, and mbx2 (orthologous to SSN3, SSN8, and the paralogs RLM1/SMP1) and MLP formation is conserved.
Of those adhesive strains, deletion of srb11 and srb10 tended to grow faster than others with similar levels of adhesion indicating that it strikes a balance between adhesiveness and slow growth that may help to explain why it exists in wild isolates driving Multicellular Like Phenotypes.
Finally Bence went above and beyond the call of duty to screen the entire S. pombe deletion collection and identified 15 genes not previously associated with Multicellular-Like Phenotypes in fission yeast, S. cerevisiae or C. albicans.
Also the mutation (and the surrounding genomic region) showed up in one of our most sticky wild isolates (JB914) even though it was overall not closely related to JB759 indicating that this mutation may exist in the population as an allele that confers MLP formation in multiple lineages.
Srb11 is the cyclin for CDK8, known as srb10 in S. pombe and it is part of the cyclin-dependent kinase module in fission yeast. We saw that deletion of srb10 or srb11 drove flocculation in an mbx2 dependent manner and that overexpression of mbx2 drove flocculation even in rich media.
Interestingly this locus did not show up when we did the QTL analysis without including those additional sequenced strains.
After sequencing several of the strains from that library that didn't make the original dataset, and that happened to be some of the most adhesive (perhaps not a coincidence?), we performed a QTL analysis and found one frameshift mutation in the srb11 gene implicated in the phenotype.
Bence had the clever idea of checking for correlation between gene expression in those strains and our Flocculation and Adhesion phenotypes and observed that the phenotypes were highly correlated with expression of the transcription factor mbx2 as well as some flocculins:
We were also lucky to have in the lab a library of segregants from a cross between the lab strain and our original sticky strain, JB759, from previous work which had associated RNA-sequencing data:
pubmed.ncbi.nlm.nih.gov/25432776/
We developed a flocculation assay in liquid media and an adhesion assay in solid media and used those assays to screen a library of natural isolates in different conditions. We saw that the propensity to form Multicellular-Like Phenotypes (MLPs) was strain and conditions dependent.
The initial observation that launched the project was of a wild isolate of S. pombe that showed flocculation in minimal media:
This project from @jbahler.bsky.social lab at @ucl.ac.uk's Genetics Evolution and Environment (GEE) department came out of a summer project from Celeste Cohen and a very productive masters project from first author @bencekover.bsky.social.
Proud of our new paper just out in the @genetics-gsa.bsky.social's #GENETICS journal academic.oup.com/genetics/adv...!
So with the ease that one can port these impressive projects do we lose some of the lab-based development of particular packages? That would be sad as a user. I would prefer for the developers of an R-based tool to manage the python version.
Congrats Max and thanks for the clear summary - looking forward to reading the full paper!
Nice new paper by Mariella Obermaier in the Ralser Lab to understand interactions between common drugs co-administered with antifungals and antifungals on C. albicans pubmed.ncbi.nlm.nih.gov/40720257/
Nice work by @maxhaase.bsky.social about the strange history of yeast centromeres - got to see him present it at #yeast2025
It’s out! The evolutionary origins of yeast point centromeres uncovered!
“Ancient co-option of LTR retrotransposons as yeast centromeres”
www.biorxiv.org/content/10.1...
Thanks Jacob for your help with this project- was great working with you!
NEW pub: The role of metabolism in shaping #enzyme structures over 400 million years. Now out in @nature.com
Super grateful to have played a small role in this project - congrats to lead/corr authors Oliver, Benjamin, and Markus!
www.nature.com/articles/s41...
#alphafold #evolution #genomics
A paper I have been working on with Oliver Lemke in the Ralser lab has just come out: www.nature.com/articles/s41...
We used predicted structures to gain insight into the evolution of metabolic proteins in yeast.
A bit more in this linked-in post (www.linkedin.com/posts/benjam...).
how (yeast) cells re-climb the fitness landscape when they are reprogrammed to a different telomere DNA sequences (human-like)? read the latest from @melaniadangiolo.bsky.social etal , with great help and insights from Eric Gilson, Jonas Warringer and @juliamuenzner.bsky.social (& Ralser lab)
Wow - amazing mito video!