Microtubules and motors in cell division
Life is all about movement. Cells, the basic units of life, show extensive internal movements that sustain the dynamic organization of the cell’s interior. Cells have to constantly explore their inner space to adjust the position of their components in a response to changes such as growth, progression through the cell cycle, and signals from the environment. To this aim cells use microtubules and actin filaments together with cytoskeleton-associated proteins.
We are interested in how motor proteins and microtubules self-organize to produce large-scale movements in the cell. The work of our lab is focused on meiotic nuclear oscillations, kinetochore capture, spindle assembly, and segregation of damaged proteins in dividing cells. Our approach is live cell imaging at the single-molecule level in fission yeast and mammalian cells, in combination with genetic and biophysical manipulations, e.g., laser ablation. We aim at quantitative descriptions and development of theoretical models that help us understand the self-organization processes in the cell.
Coelho, Miguel; Lade, Steven J.; Alberti, Simon; Gross, Thilo; Tolić, Iva M.
Coelho, Miguel; Dereli, Aygül; Haese, Anett; Kühn, Sebastian; Malinovska, Liliana; DeSantis, Morgan E.; Shorter, James; Alberti, Simon; Gross, Thilo; Tolić-Nørrelykke, Iva M.
Ananthanarayanan, Vaishnavi; Schattat, Martin; Vogel, Sven K.; Krull, Alexander; Pavin, Nenad; Tolić-Nørrelykke, Iva M.
Kalinina, Iana M.; Nandi, Amitabha; Delivani, Petrina; Chacón, Mariola R.; Klemm, Anna; Ramunno-Johnson, Damien; Krull, Alexander; Lindner, Benjamin; Pavin, Nenad; Tolić-Nørrelykke, Iva M.
Stiess, Michael; Maghelli, Nicola; Kapitein, Lukas C; Gomis-Rüth, Susana; Wilsch-Bräuninger, Michaela; Hoogenraad, Casper C; Tolić-Nørrelykke, Iva M.; Bradke, Frank
Vogel, Sven; Pavin, Nenad; Maghelli, Nicola; Jülicher, Frank; Tolić-Nørrelykke, Iva M.
A complete list of publications can be found here.
What happens when you inherit all your parents' junk
During their lifetime, cells accumulate damage that is inherited by the daughter cells when the mother cell divides. The amount of inherited damage determines how long the daughter cell will live and how fast it will age. We have discovered fusion of protein aggregates as a new strategy that cells use to apportion damage asymmetrically during division. By combining live-cell imaging with a mathematical model, we show that fission yeast cells divide the damage equally between the two daughter cells, but only as long as the amount of damage is low and harmless. However, when the cells are stressed and the damage accumulates to higher levels, the aggregated proteins fuse into a single clump, which is then inherited by one daughter cell, while the other cell is born clean. This form of damage control may be a universal survival strategy for a range of cell types, including stem cells, germ cells, and cancer cells.
Weekly Editors' Picks: Stressed Yeast Paint a Picture of Dorian Gray by Roland G. Roberts PDF
A yeast that does not age
Do all organisms age? All single-cell organisms studied so far undergo aging. For example, when a cell of the baker's yeast divides, the mother cell receives older, often defective, cell material, whereas the daughter cell is equipped with new fully-functional material. We have shown that, unlike other species, the fission yeast S. pombe is immune to aging when reproducing under favorable growth conditions. Interestingly, these cells undergo a transition from non-aging to aging upon stress. This transition may have evolved to sacrifice some cells so that others may survive unharmed after severe environmental stresses.
Highlighted in Science (volume 342, page 164) Editors' Choice PDF
Dispatch in Current Biology by James Moseley PDF
Press Release of the Max Planck Society (in German)
Dynein motors caught in the act
Cells have a fascinating feature to neatly organize their interior by the use of motor proteins. The motor protein cytoplasmic dynein drives a variety of motile processes, such as the transport of organelles and mRNAs, and the formation of the mitotic spindle. Yet, little is known about the behavior of individual dyneins in vivo. We have been successful in observing individual dynein motors as they move throughout the cell, bind to and move along the microtubule. We uncovered a two-step binding process where dynein binds first to the microtubule and then also to the cortical anchor protein. Our study further reveals that dyneins target cortical anchors by diffusing along the microtubule and switch to directed movement upon binding to the anchor. These single-molecule observations thus bring the pieces of the puzzle together into a complete picture of the dynein behavior in vivo.
Microtubules search for kinetochores by pivoting
During cell division, spindle microtubules attach to chromosomes through kinetochores, protein complexes on the chromosome. The central question is how microtubules find kinetochores. By combining experiments with theory, we have discovered a new search mechanism: Microtubules swipe through the cell and thus explore the space in search for kinetochores, until they approach a kinetochore and capture it. This search strategy is cost-effective for the cell, because it requires only a small number of microtubules and does not need energy from ATP. In general, microtubules may probe the space laterally in various cellular contexts, as their search for intracellular targets such as chromosomes.
Press Release of the Max Planck Society (in German)
Dynein distribution is mechanically regulated to drive nuclear oscillations
A key aspect of life is sexual reproduction, which requires concerted movement (in the cell). For successful mixing of the genetic material, molecular motors have to move the nucleus back and forth inside the cell. We have observed and described mathematically how motors self-organize to produce these fascinating large-scale movements.
In 2009, Marcus Anhäuser received the Dresden Journalist in Residence Fellowship of the three Dresden Max Planck Institutes. At the MPI-CBG, he was hosted by the lab of Iva Tolic-Nørrelykke and wrote a daily online science blog about their work entitled Lab Diary.
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