The role polyglutamylation in tauopathic neurodegeneration

Lab's research themes:

We are a team of microtubule enthusiasts aiming at understanding how microtubules adapt to many different functions in living cells.

We use an interdisciplinary approach to understand how microtubules are regulated at the molecular level to control their functions in cells, and how this contributes to organism homeostasis. We want to understand how dysfunctions of these mechanisms lead to diseases, such as neurodegeneration, cancer, or male infertility.

Merits of the lab:

My team has discovered a large number of enzymes that catalyse tubulin polyglutamylation and polyglycylation (Janke et al., Science 2005; van Dijk et al., Mol Cell 2007; Rogowski et al., Cell 2009; Rogowski et al., Cell 2010), thus for the first time allowing to study these enigmatic modifications that had initially been discovered in the 1990ies.

My team demonstrated that tubulin modifications act mostly as fine-regulators of MT functions, and are thus important for homeostasis. We discovered the importance of tubulin polyglutamylation and glycylation for neuronal homeostasis and its implication in neurodegeneration (Magiera et al., EMBO J 2018; Shashi et al., EMBO J 2018), male fertility (Giordano et al., J Cell Sci 2019; Gadadhar et al., Science 2021), ciliary functions (Bosch Grau et al., J Cell Biol 2013; J Cell Sci 2017; Gadadhar et al., J Cell Biol 2017) and cancer (Rocha et al., EMBO J 2014).

The work of my team has further driven the development of novel technologies, such as the purification of unmodified tubulin to study the impact of tubulin posttranslational modifications by in-vitro reconstitution assays (Souphron et al., Nat Protoc 2019, Jijumon et al., Nat Cell Biol 2022).

The concept we develop in my team can help researchers to overcome the barrier between molecular studies and physiology. It can deliver novel insights on how apparently insignificant molecular alterations play a key role in the life of an organism, and how these events, if perturbed, can cause late-onset diseases in humans.

Why do we want medical doctors?

Our team is mostly anchored in basic research; however, our recent discoveries show the key importance of the molecular mechanisms we are working on for medical research (Shashi et al., EMBO J 2018). We thus believe that working with a medical doctor on this project would allow us to establish closer links to the clinic, while the PhD student would greatly profit from our interdisciplinary research experience.

The position