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“Mitotic spindle: From living and synthetic systems to theory” #SpindleCroatia2021 starts tomorrow! We are running the final preparations and enjoying the view from the rooftop terrace of the conference hotel Cornaro. pic.twitter.com/mBdGlb3C6S
— Tolić lab (@Toliclab) March 27, 2021
The conference #SpindleCroatia2021 is open! Wish you were all here with us in Split! https://t.co/Hi3FwHyAIz pic.twitter.com/9XOAT2papl — Tolić lab (@Toliclab) March 28, 2021
Grand start of #SpindleCroatia2021 today by Alexey Khodjakov, who showed that formation of kinetochore fibers is driven by short non-centrosomal microtubules, sorted by CENP-E, and bundles of antiparallel microtubules on the surface of the spindle.
— Tolić lab (@Toliclab) March 28, 2021
Alex Mogilner showed incredible 3D simulations of the Search-and-Capture mechanism, revealing that rapid microtubule turnover at kinetochores, deformable centromeres, and chromosome positioning near the spindle equator are important for spindle assembly. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 28, 2021
Nandini Mani from Radhika Subramanian’s Lab showed what happens when you mix PRC1, CLASP1, and Kif4A. On single microtubules, CLASP1 wins due to its higher activity, but on bundled microtubules Kif4A wins because of its recruitment by PRC1. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 28, 2021
Alessandro Dema from @WittmannTorsten lab showed cool optogenetic experiments in which EB1 photoinactivation increased astral microtubule number and length, likely due to Kif18B removal. Spindles shortened and moved away from the light-exposed areas. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 28, 2021
Chip Asbury showed that microtubule pivoting is crucial for spindle assembly in S. cerevisiae. They designed Spc110 mutants that alter the pivoting flexibility of microtubules about purified spindle poles, and found that they affect pole separation in vivo. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 28, 2021
David Odde @DavidOddeLab used multiscale modeling of microtubule assembly, starting with an atomic-level structure as input. They found that GTP hydrolysis results in longitudinal bond weakening and an outward bending preference, driving dynamic instability. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 28, 2021
Patrik Risteski @risteski_ @Toliclab showed that microtubule poleward flux promotes chromosome alignment. A longer kinetochore fiber has faster poleward flux due to larger overlap with bridging microtubules, centering an off-centered chromosome. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 28, 2021
Rebecca Heald @rebeccaheald discussed mitotic chromosome scaling, how they get smaller as the cells get smaller. In their cool single-molecule experiments they stretch DNA by optical tweezers and study subsequent compaction. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 28, 2021
Julien Dumont showed that critical kinetochore components are different between mitosis and holocentric meiosis. Simultaneous loss of Ndc80 attachments and suppression of kinetochore microtubule dynamics recapitulated the kinetochore-null phenotype. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 28, 2021
Olga Afonso @OlgaAfonso_ from @MGG_lab asked how chromosome segregation and nuclear envelope reformation adapt to cell size. Cytoplasmic flows appear close to chromosomes, scale with cell size and correlate with chromosome velocity. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 28, 2021
Good night, #SpindleCroatia2021! What a vibrant and exciting first day! See you all tomorrow! pic.twitter.com/DIHylmefTY
— Tolić lab (@Toliclab) March 28, 2021
Happy birthday to our marvellous moderator Juraj Simunic! #SpindleCroatia2021 pic.twitter.com/XXU3cZSYn4 — Tolić lab (@Toliclab) March 29, 2021
Sophie Dumont @DumontLab started Day Two of #SpindleCroatia2021 with her exciting story about the role of opposing motors in mechanical and functional robustness of the spindle. NuMA & Eg5 inhibited spindles are mechanically fragile and extremely twisted!
— Tolić lab (@Toliclab) March 29, 2021
Francois Nedelec discussed how to make antiparallel microtubule overlaps. He showed a theory of how microtubules connected by crosslinkers (PRC1) and motors (Kif4A) form stable and mechanically strong overlaps, with traffic jam playing an important role. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 29, 2021
Geng-Yuan (Scott) Chen @asdScott0331 from Lampson Lab used optogenetics to manipulate Aurora B at individual kinetochores. He found that at high tension, Aurora B promotes microtubule release, whereas at low tension it promotes depolymerization. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 29, 2021
Geng-Yuan (Scott) Chen @asdScott0331 from Lampson Lab used optogenetics to manipulate Aurora B at individual kinetochores. He found that at high tension, Aurora B promotes microtubule release, whereas at low tension it promotes depolymerization. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 29, 2021
Alex Thompson @alexfthompson from Jason Stumpff lab @jstumpffVT showed that pathogenic mutations in the chromokinesin KIF22 disrupt anaphase chromosome segregation. Chromosomes start to segregate, but then re-congress due to polar ejection forces. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 29, 2021
Susanne Lens @LensSusanne coupled a minus-end directed motor to a specific chromosome to drive its mis-segregation! Plant Kin14VIb was recruited to TetO repeats on the chromosome arm. These arms moved to the pole and co-segregated into the same daughter cell! #SpindleCroatia2021 — Tolić lab (@Toliclab) March 29, 2021
Sarah McClelland @McclellandLab assembled an ectopic kinetochore by using CENP-T. This led to mis-segregation of specific chromosomes, which they will use to study consequences of these errors. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 29, 2021
Ivana Ban from Nenad Pavin’s group @nenad_pavin presented a mathematical model that explains tumor karyotypes by chromosome segregation errors together with increased proliferation. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 29, 2021
Phong Tran showed that the velocity of spindle elongation in S. pombe is regulated by the amount of kinesin-6 Klp9, which increases with cell size, resulting in faster elongation. He also proposed that the short mitosis duration protects cells from DNA damage. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 29, 2021
Paula Real-Calderon from Fred Chang’s lab used spindle bending in S. pombe as an in vivo force sensor. Bent spindles were made by oscillations in sorbitol. The spindles break at the midzone or pole, due to elongation forces. Bending depends on Ase1/PRC1. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 29, 2021
Nigel Burroughs developed an error-correction model merging tension-clock model with decision making. Spring force control and corona dynamics can reproduce low attachment error rates. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 29, 2021
In the heart of Split #SpindleCroatia2021 pic.twitter.com/06aONib5NA — Tolić lab (@Toliclab) March 30, 2021
Day 3 of #SpindleCroatia2021 started with Gohta Goshima asking how can an organism lose an essential gene. By activating a “masked” mechanism! For example, fission yeast without Polo kinases can be viable, as mutations in a downstream microtubule nucleator/stabilizer bypass Polo.
— Tolić lab (@Toliclab) March 30, 2021
Sabine Petry @LabPetry showed that the hydrodynamic Rayleigh-Plateau instability causes TPX2 to form regularly spaced droplets on microtubules, like water droplets on a spider web. TPX2 droplets co-condensate with tubulin and nucleate microtubule branching. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 30, 2021
David Oriola @davidhbp @brugueslab combined speckle microscopy, laser ablation and simulations to show that a gelation transition enables long-ranged microtubule flows causing spindles to self-organize into two oppositely polarized microtubule gels. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 30, 2021
Manasi Kelkar @manasikelkar09 from @G_Charras lab used optogenetics to locally modulate cortical tension. The spindles rotated away from myosin-enriched stiff cortical regions, positioning the division axis towards regions of lower cortical stiffness. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 30, 2021
Duane Compton @CINchromosome measured Hec1 phospho-occupancy by mass spectrometry. Phospho-occupancy is inherently low. Small changes in phosphorylation induce large changes in microtubule attachment, controlling chromosome segregation fidelity. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 30, 2021
Dileep Varma @DileepVarmaLab showed that Ska binds to Cdt1 and enables its docking to the Ndc80 complex, leading to the formation of a tripartite Ndc80-Ska-Cdt1 complex. This synergy may be important for robust end-on kinetochore-microtubule attachments. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 30, 2021
Veronique Marthiens from @basto_lab showed that in embryonic neural stem cells, spatial constraints lead to high density of astral microtubules and spindle geometry favoring abnormal kinetochore attachments, which results in chromosome segregation errors. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 30, 2021
Karsten Kruse discussed, from a theoretical point of view, microtubule length regulation by motor-dependent modifications of the microtubule shaft. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 30, 2021
Charlotte Aumeier showed that kinesin-1 walking on microtubules causes exchange of dimers along the shaft. These sites act as rescue locations, leading to increased microtubule length. In cells, increased motor activity results in denser microtubule networks. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 30, 2021
Emmanuel Nsamba @nsamba_emmanuel from Gupta lab made yeast expressing single tubulin isotypes, Tub1 or Tub3, and showed that this affects mitotic motors. Kinesin-14 bound to Tub3-only spindles, making them short, and kinesin-5 to Tub1-only, making them long. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 30, 2021
Emmanuel Nsamba @nsamba_emmanuel from Gupta lab made yeast expressing single tubulin isotypes, Tub1 or Tub3, and showed that this affects mitotic motors. Kinesin-14 bound to Tub3-only spindles, making them short, and kinesin-5 to Tub1-only, making them long. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 30, 2021
Good night, spindle lovers! Thank you for another exciting day at #SpindleCroatia2021! pic.twitter.com/STKrixzQy5 — Tolić lab (@Toliclab) March 31, 2021
Discussions over coffee in a labyrinth of narrow streets and alleyways in the historical center of Split #SpindleCroatia2021 pic.twitter.com/CINiD3I3Di
— Tolić lab (@Toliclab) March 31, 2021
Claire Walczak @clairewalczak started the last day of #SpindleCroatia2021 by showing that the Ran pathway is critical to promote kinesin-14 parallel microtubule crosslinking for bipolar spindle assembly and pole focusing. This could help cancer cells cluster their centrosomes. — Tolić lab (@Toliclab) March 31, 2021
Meredith Betterton asked how can motors measure the length of a microtubule that is 10x longer than the motor run length. Motors can sense and respond to motors bound several microns away on a microtubule! Microtubule is a dynamic medium like a wooden bridge. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 31, 2021
April Solon from @R_Ohi_Lab examined regulation of the kinesin motor activity by kinesin-binding protein (KBP). She determined high-resolution structures of KBP bound to Kif15 and Kif18A and identified regions critical for the interaction. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 31, 2021
Tarun Kapoor revealed how the proteins of -TuRC are organized into an asymmetric cone. They biochemically reconstituted the human -TuRC! The intriguing “lumenal bridge” helps self-assembly of regulatory interfaces around a microtubule-nucleating “core”. #SpindleCroatia2021
— Tolić lab (@Toliclab) March 31, 2021
Do microtubules pierce mitotic chromosomes? Daniel Gerlich @gerlich_daniel beautifully showed that global deacetylation of mitotic chromatin results in the formation of a microtubule impermeable surface on mitotic chromosomes. #SpindleCroatia2021 — Tolić lab (@Toliclab) March 31, 2021
Nuria Ferrandiz @Nufediaz from @roylelab showed that chromosomes that remain close to the spindle pole can become ensheathed in layers of endomembranes, resulting in missegregation. Pulling of endomembranes to the cell membrane rescues the missegregation! #SpindleCroatia2021
— Tolić lab (@Toliclab) March 31, 2021
Arshad Desai @Protofilament @oegemadesai_lab used the PLK4 inhibitor centrinone and showed that centrioles and the pericentriolar material can separately generate spindle microtubules. Acentrosomal spindle assembly is controlled by the ubiquitin ligase TRIM37. #SpindleCroatia2021 — Tolić lab (@Toliclab) April 1, 2021
Daniela Cimini used DLD-1 tetraploid clones to link SAC silencing and cell/spindle size. Spindle size does not always scale with cell size. Small clones have prolonged metaphase, which can be explained by spindle architectural features along with cell size. #SpindleCroatia2021
— Tolić lab (@Toliclab) April 1, 2021
In a closing talk of #SpindleCroatia2021, David Pellman discussed how genome evolution can be driven by burst-like mutational processes caused by cell division errors. This can lead to cytoplasmic chromatin, which can be damaged by an aberrant form of DNA base excision repair. — Tolić lab (@Toliclab) April 1, 2021
Thank you all for sharing so much exciting science at #SpindleCroatia2021, for staying on zoom for hours every day, for the passionate discussions and liveliest poster sessions we’ve seen over the past year. We look forward to hosting you for real in Split on #SpindleCroatia2023! pic.twitter.com/RgnVmJfdrm
— Tolić lab (@Toliclab) April 1, 2021