Hypothesis Retrofitting.
Scientific papers are more complex than ever, but are we gaining deeper understanding or losing sight of the hypothesis?

In my opinion, a very well articulated viewpoint.

network-febs-org.cdn.ampproject.org/c/s/network....

COS7 cells labeled for actin (gray), microtubules (orange) and clathrin (blue). The two middle cells are dividing, with a reorganisation of microtubules into a spindle and denser clathrin assemblies. Image taken with an Apotome microscope.

Busy #cellfie 🧪

Mitosis is truly the most beautiful cellular process to image 😍

Nature’s laboratory - Works in Progress Magazine Millions of years of evolution have given us genomes that are like giant datasets for drug development. Finally, we are learning how to study them.

Very insightful synthesis of ideas and lessons on how human genetics is used to shape drug development @worksinprogress.bsky.social

worksinprogress.co/issue/nature...

Thrilled to share our new paper describing the development and characterization of CDK11 inhibitors for cancer therapy. We also establish a new system that I think represents a huge leap forward in our ability to understand drug toxicity in a living organism.

A pivot-tether model for nucleosome recognition by the chromosomal passenger complex | EMBO reports imageimageAurora B is targeted to chromatin subdomains by the chromosome passenger complex, formed by survivin, borealin and INCENP. Spatial restriction of Aurora B adjacent to kinetochores is importa...

Work from the Barr lab @oxfordbiochemistry.bsky.social keeps on coming. Fantastic mechanistic work!

Time as a danger signal promoting G1 arrest after mitosis Cell cycle checkpoints preventing the replication and inheritance of damaged DNA are crucial for maintaining genome stability and stopping the growth of damaged cells. Canonical checkpoints do this by preventing passage between cell cycle phases until damage has been repaired, or by promoting cell cycle exit. Herein we review checkpoint integration between cell cycle phases, specifically findings showing that extended spindle assembly checkpoint surveillance in mitosis is a danger signal triggering G1 cell cycle arrest. Evidence linking mitotic delays induced by activation of the spindle assembly checkpoint with positive and negative regulators of the G1 DNA damage checkpoint target p53 is discussed, with a focus on time-dependent changes to a p53-binding deubiquitinating complex USP28–53BP1 and the p53 ubiquitin-ligase mouse double minute homologue 2 (MDM2), respectively.

Time as a danger signal promoting G1 arrest after mitosis

WIP1 mutations suppress DNA damage triggered bypass of the mitotic timer | The EMBO Journal imageimageProlonged delays in mitosis and G2 DNA-damage stress both lead to cell-cycle arrest in G1. This work shows how these pathways normally lead to G1 arrest by different routes, and how cancer-a...

Happy to share our latest work from the Barr lab is now published in @embojournal.org

👉 WIP1 mutations suppress DNA damage triggered bypass of the mitotic timer | EMBO Journal

#cellcycle
@oxfordbiochemistry.bsky.social

www.embopress.org/doi/full/10....

New definition of leaving a mark.

Lot of work to do, but thanks to investors, we hope to bring ASOs for RNA editing to the clinic. Let's do this! #RNAtherapeutics #RNAediting #biotech

News: AIRNA: Harnessing the Body’s RNA-Editing System for Therapeutic Applications - CRISPR Medicine Boston- and Germany-based biotech startup AIRNA is pioneering a new approach to genetic medicine by harnessing the body's natural RNA-editing machinery. Building on more than a decade of research in A...

RNA editing has a lot of potential yet to be uncovered. We'll find out how to use it to cure diseases.

A pivot-tether model for nucleosome recognition by the chromosomal passenger complex Spatial restriction of Aurora B to centromeres during prometaphase and metaphase enables it to phosphorylate proteins necessary for spindle assembly checkpoint signalling and biorientation of chromoso...

Fabulous work from our colleagues in the Barr lab showing how the CPC binds the nucleosome!

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

MDM2 functions as a timer reporting the length of mitosis - Nature Cell Biology Fulcher et al. show that MDM2 times mitosis through self-catalysed ubiquitination and proteasomal destruction, triggering G1 arrest following delays in mitosis associated with chromosome instability a...

This paper from the Barr lab @oxfordbiochemistry.bsky.social is 🔥. MDM2 levels fall during mitosis due to short protein half life. When cells spend too much time in mitosis, too much MDM2 degradation occurs. As a result, p53 stabilizes triggering G1 arrest.
www.nature.com/articles/s41...