While some cell biologists might intuitively feel uncomfortable with extensive diversity within groups, they should question their intuition in the face of overwhelming evidence for phylogenetic monophyly. We welcome constructive discussion with anyone willing to study the opposing arguments. (3/X)
While the root is not fully resolved, the validity of phylogenomics to uncover deep evolutionary relationships is unquestionable. This approach unequivocally shows a monophyly of Euglenozoa invalidating the hypothesis that kinetoplastids/glycomonads split first from all other living eukaryotes.(2/3)
As a cell biology lab, we acknowledge the decades-long impressive efforts to uncover evolutionary relationships using advanced phylogenomics methods. These approaches undergo continuous improvements that lead to adjustments of data interpretation, as is the case in every scientific field. (1/3)
Recently, a Hypothesis was posed in @jcellsci.bsky.social in which the root of eukaryotes was placed between kinetoplastids and all other eukaryotes. From this, it was implied that LECA did not have a kinetochore. We argue this is highly unlikely. A 🧵(1/12)
Read our reply here: tinyurl.com/n87myhpr
New preprint from our lab! Led by Emine Ali and @maxraas.bsky.social
See the highlights below!
Our story on the kinetochore composition of the ciliate Tetrahymena thermophila is out now on bioRxiv! We find surprisingly many orthologs of conventional kinetochore components, but also components that have very different evolutionary origins. A 🧵 (1/11)
Check it out here: tinyurl.com/4ectm9x4
Surprise — it wasn’t: RNA-seq and histology show that moderate/high CIN causes massive cell death, triggering regeneration without immune infiltration — providing the non–cell-autonomous push that fuels tumorigenesis. (5/5)
One possibility of such a mechanism: CIN may mimic TPA in promoting tumorigenesis. Indeed, moderate/high CIN could partially replace TPA in the DMBA/TPA regimen.
But what TPA effect was CIN mimicking? Inflammation? (4/5)
Now the twist: despite being induced under moderate/high CIN, these tumors are made of low CIN cells across other tumor types.
So what’s happening?
Moderate/high CIN drives the outgrowth of rare low-CIN tumor cells through a non–cell-autonomous mechanism which doesn't happen in only low CIN. (3/5)
CIN levels matter!
We used CiMKi mice to induce and monitor skin tumors across five CIN levels in combination with DMBA/TPA treatment.
Low → more tumors but no effect on onset or growth
Moderate → more tumors earlier onset and larger growth
High → fewer tumors but earlier and earlier growth (2/5)
Ever wondered how chromosomal instability (CIN) influences tumorigenesis? And how does it contribute to shaping the tumor microenvironment?
In our latest preprint, we used the CiMKi model to induce and monitor skin tumors across five levels of CIN
tinyurl.com/52tuk88z
Here's what we find (1/5):
Ready to establish your own research group at the Hubrecht Institute for Molecular and Developmental Biology? We’re seeking a tenure-track group leader to develop an innovative research line within our vibrant scientific community. Learn more & apply! https://f.mtr.cool/jncxfqkuds
Altogether, our findings highlight the need to explore the tissue context of p53 responses to aneuploidy. We propose that future efforts should integrate the use of appropriate models of diverse healthy and pre-cancer human tissues.
(8/8)
Finally, we show that losses, but not gains, are more universally linked with p53 deficiency across cancer types. This association has been previously made and highlights an exciting direction to explore the role of p53 responses to aneuploidy.
(7/8)
Surprisingly, we find that neither arm-level or whole-chromosome CNAs correlate with p53 deficiency. This is particularly interesting given the role of p53 in responding to DNA damage, which is often linked to arm-level copy number alterations.
(6/8)
This lead us to ask the following question: can specific features of aneuploidy better distinguish p53 proficient and deficient tumors? To explore this we focused on the type (arm- or whole-chromosome) and direction of copy-number alteration (CNA).
(5/8)
We were excited to find that p53 inactivation is neither sufficient nor necessary for tumors to accumulate a high degree of aneuploidy. We find that tumors with high aneuploidy yet intact p53 are common, and also that p53 inactivation does not invariably lead to highly aneuploid tumors.
(4/8)
To fully capture the p53 status we defined p53 deficiency as either TP53 mutations or alterations that phenocopy TP53 loss. Aneuploidy was defined as arm- or whole-chromosome copy number alterations (CNAs).
(3/8)
Despite decades of research, it is still unclear whether p53 protects against particular forms of copy number alterations and whether it does so universally across cancer types. To investigate this we systematically analyzed TCGA tumors across 31 cancer types.
(2/8)
Our new preprint is out! We revisit the associations between p53 status and cancer aneuploidy using TCGA data. Here’s a breakdown of our findings. Important work spearheaded by the talented PhD candidate Joana Marques. Check it out here: www.biorxiv.org/content/10.1...
(1/8)🧵
A few weeks ago, we said goodbye to long-term Kops lab member Emine Ali, our resident protistologist.
We wish Emine all the best in her future career.
Spending a few days in beautiful Heidelberg for the 5th EMBL partnership conference. Our Hubrecht institute is EMBL partner and it has been wonderful to see the exciting science of the other partner institutes! @embl.org @hubrechtinstitute.bsky.social
An amazing inaugural Hubrecht Symposium on Developmental Biology, bringing the Dutch community together and getting inspired by amazing science! A big thank you to the speakers, the organizing committee and the many dedicated Hubrechters who made it happen.
🚀Ever wondered if there's a universal rule of spindle scaling across eukaryotes? Turns out, there is! Our study reveals an evolutionarily conserved principle driven by a surprising factor: chromosome crowding. 🧵👇
shorturl.at/MmPNr
Expression of the timing protein LIN-39 (green) in C. elegans
How do cells measure time? Despite its fundamental role in development, the underlying mechanisms remain unclear. An NWO ENW-XL grant allows a research consortium from the Hubrecht Institute, AMOLF, TU Delft, and ENS Paris to study timing regulation in C. elegans. www.hubrecht.eu/how-do-cells...
Phylogenetic profile of CENP-E across holocentric and monocentric taxa. (A–D) CENP-E conservation in (A) the phylum Nematoda, (B) the phylum Vertebrata, (C) the insect order Hemiptera and (D) the insect order Diptera. Lineages with an inferred CENP-E loss are highlighted with a coloured box. Holocentric lineages are indicated with ‘H’ and monocentric lineages with ‘M’, as well as with a graphic depiction of holocentric and monocentric chromosomes.
Ana Almeida, Helder Rocha, Maximilian Raas, Geert Kops, Reto Gassmann, Helder Maiato @i3suporto.bsky.social, et al. dissect the relationship between kinetochore size & CENP-E dependence for chromosome alignment.
journals.biologists.com/jcs/article/...
journals.biologists.com/jcs/article/...
