Publication highlights

An international group of researchers from the Crick, Imperial College London, Waseda University and the Cancer Institute of the Japanese Foundation for Cancer Research have redrawn the idea of chromosome shape, finding that they’re not always stable X-shaped structures but are constantly in flux as cell division takes place. They live-imaged chromosomes over time, observing that they become continuously shorter and thicker, and that they are aiming for a 'final roundness' - a ratio of length and width that's the most physically stable. Using computer simulations, they showed that longer chains reach far longer to reach a stable length, suggesting that they aren't in a steady state at cell division, whereas shorter chains reach a steady state almost straight away. The team conclude that the length of time chromosomes spend in mitosis dictates whether they will all reach a final shape or not.

Cryopreservation methods for archiving and distributing mouse strains mostly focus on freezing embryos or sperm. In contrast, the cryopreservation of oocytes (eggs) is not widely adopted in large biomedical research facilities, due to highly variable results and challenges in validating methods to preserve genetically modified oocytes on a large scale. The Genetic Modification Service at the Crick has developed a robust vitrification protocol for large-scale oocyte cryopreservation, achieving high viability and fertilisation rates comparable to fresh oocytes. They have extensively tested the protocol for in vitro fertilisation of 13 genetically altered strains, using both genetically altered and wild-type oocytes and sperm. Combining these genetically modified cryopreserved oocytes with an archive of cryopreserved sperm allows the generation of embryos with different genetic combinations. This potentially reduces subsequent breeding steps and the need to maintain live stocks of certain mouse strains.

During development, cells acquire cell fates with remarkable precision and reliability. This is exemplified in insect wings, which form a highly stereotypical vein pattern. Molecular markers suggest that vein fates are specified during larval stages, when wing primordia still undergo growth and morphogenetic movements. Previous work has shown that the initial vein pattern can be compared to broad brush strokes that are subsequently refined to make up the final picture. Using live reporters of cell fate and signalling activity, combined with mathematical modelling, researchers at the Crick and the University of Geneva show how a network of three well-known signal transduction pathways continuously update the vein fate to ensure reproducible vein formation despite the complex flows associated with tissue rearrangements.

Sister chromatids of DNA are held together by a ring-shaped protein complex called cohesin, and scientists have long pondered how the DNA-copying machinery manages to navigate genetic strands while encountering cohesin rings. After finding that the replisome can travel through the cohesin ring, a multidisciplinary team of researchers at the Crick investigated sister chromatid cohesion in more detail. They often observed that cohesin hugged just a single DNA copy after replication, and that a structure called the 'cohesin loader' appears to intervene and bring the second chromatid into the ring. They also showed that sometimes more cohesin molecules are used, bringing together the chromatids in a two-step process involving additional cohesin molecules to those present before replication.

Gene regulatory networks play a central role in shaping spatial patterns: the lines that eventually give rise to segments, organs or markings like stripes and spots. Researchers at the Crick explored whether specific types of mutations in patterning networks accelerate the evolution of new patterns, and if any of these changes yield predictable evolutionary outcomes. Using a computer simulation that models how small networks of genes evolve under natural selection, they found that adjusting an existing boundary needed only small tweaks to the strengths of existing gene interactions. But creating new boundaries was far more difficult, demanding multiple changes at once. They also found that certain mutations radically shift the predicted evolutionary outcome, suggesting that a mutation introduces a fork in the road early on which reliably redirects evolution to a specific destination.

Sister chromatids of DNA are held together by a ring-shaped protein complex called cohesin, and scientists have long pondered how the DNA-copying machinery manages to navigate genetic strands while encountering cohesin rings. A multidisciplinary team of researchers at the Crick use a biological reconstitution method to explore this. When they loaded cohesin onto DNA and added the replisome, in some cases they witnessed the replisome travelling through the ring. Additionally, the more replisome components they added, the more efficiently the complex passed through the rings, despite its increased size. Finally, the team showed that the components responsible for helping the replisome pass through the cohesin ring where DNA polymerase enzymes. In a complimentary paper, they also showed that there are other ways for the replisome to bypass cohesin rings.