Past events with invited speakers

Tim Mitchison is from Harvard Medical School. In 1984, he discovered that microtubules are dynamic and thus established microtubule research field as we know it today.  

Carsten Janke, from Institut Curie, is one of the leading scientists in the field, describing how microtubule systems are regulated by the tubulin code.

Abstract: Diversifying cytoskeletal functions with the tubulin code

Microtubules are highly versatile cytoskeletal fibres that fulfil essential functions in every eukaryotic cell. Despite this functional diversity, microtubules and their basic building blocks - the tubulin proteins - are highly conserved throughout evolution. One of the key questions in biology is thus how microtubules can adapt to different functions. I will present how a mechanism called the Tubulin Code contributes to the functional diversification of the microtubule cytoskeleton. 

Tubulin is expressed from different genes (isotypes) and abundantly posttranslationally modified. While this molecular diversity does in most cases only subtly change the behaviour of the microtubule cytoskeleton at the molecular level, it appears that it has strong impacts at the organism and lifetime scale. 

Our lab uses mouse models in which single or multiple tubulin-modifying enzymes are knocked out to determine their physiological functions. We demonstrated that alterations in the tubulin modification glutamylation causes neurodegeneration with defects in axonal cargo transport. Changes in glutamylation can also lead to male infertility and retina degeneration. When we abolished another modification, glycylation, we observed male subfertility in mice with sperm swimming along abnormal trajectories. These finding strongly underpin the role of the tubulin code for organism homeostasis. Our current focus is to determine the molecular mechanisms underlying those physiological functions, which we do in a combination of in-vitro reconstitution and cell-biology experiments.

Polarized cells rely on a polarized cytoskeleton for polarized trafficking, oriented migration and spindle orientation. For instance, during asymmetric cell division, the anaphase midzone becomes asymmetric, with more microtubules on one side than the other, which polarizes the segregation of signalling endosomes containing cell-fate determinants to only one daughter cell, thus contributing to cell fate determination.  Here, I will discuss ongoing work from my lab to unravel the molecular mechanisms of anaphase midzone symmetry breaking, combining in vitro reconstitution of cytoskeleton dynamics, genetic screens in flies, and a synthetic biology approach aiming at reconstituting artificial polarity in unpolarised cells. Specifically, we found that central spindle asymmetry is conserved from flies to mammals and arises downstream of cortical phosphorylation by the aPKC subunit of the Par complex via Elongator, Kinesin13 and CAMSAP/Patronin. 

During cell division, the mitotic spindles self-assembles which requires the activities of microtubule nucleators, antagonistic molecular motors and regulators of microtubule dynamics. The design principles of such self-organized cytoskeletal architectures are however still not understood. To develop a mechanistic understanding of cytoskeletal self-organization based on basic biophysical and biochemical principles, we reverse-engineer dynamic sub-architectures of the human microtubule cytoskeleton. Using in vitro experiments with purified proteins and computer simulations, we explore the possible morphological organisations accessible with plus or minus-end directed mitotic motors, microtubule nucleators and depolymerases. Our results provide new insight into the morphogenetic potential mitotic cytoskeletal subsystems, helping to understand the molecular design principles of mitotic microtubule architectures.