Kiebler Lab

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Prof. Dr. Michael Kiebler

+49 89 2180 75884
michael.kiebler@med.uni-muenchen.de

Research Topics

• RNA-binding proteins in neurogenesis and synaptic plasticity
• RNA transport and local translation
• Synapses and their role in learning and memory

Publications

https://orcid.org/0000-0002-8850-6297

Top 5 Publications

Kiebler MA and KE Bauer (2024) RNA granules in flux: dynamics to balance physiology and pathology (review), Nature Rev. Neurosci. 25, 711 (Sept 30 2024)

Ehses J, Schlegel M, Schröger L, Schieweck R, Derdak S, Harner M, Bilban M, Harner M, and Kiebler MA (2022) The dsRBP Staufen2 governs RNP assembly of neuronal Argonaute proteins. Nucl. Acid Res. 50, 7034-47.

Bauer KE, Bargenda N, Schieweck R, Illig C, Segura I, and Kiebler MA (2022). RNA supply drives physiological granule assembly. Nature Comm.13, 2781.

Schieweck R, Riedemann T, Forné I, Harner M, Bauer KE, Rieger D, Ang Fy, Hutten S, Demleitner A, Popper B, Derdak S, Sutor B, Bilban M, Imhof A, and Kiebler MA (2021) Pumilio2 and Staufen2 selectively balance the synaptic proteome (Resource), Cell Rep. 35, 109279.

Bauer K, Segura I, Gaspar I, Scheuss V, Illig C, Ammer G, Hutten S, Basyuk E, Fernandez-Moya SM, Ehses J, Bertrand E and Kiebler MA (2019). Live cell imaging reveals 3’-UTR-dependent mRNA sorting to synapses. Nature Comm. 10, 3178.

Research Topics

A long-term goal of the Kiebler lab is to understand the molecular basis of synaptic plasticity with a specific focus on RNA and its cognate RNA-binding proteins RBPs). The center of our interest is how individual synapses, the point of contact and communication between neurons, are altered during their lifetime and how this contributes to our ability to learn and remember. Here, RBPs) play essential roles both during development as well as during synaptic plasticity. In particular, we have focused on a series of RBPs, e.g. Staufen2, Pumilio2, Argonaute2 and DDX6/Rck and investigated their role(s) in dendritic RNA localization and translational control at the synapse. A second and more recent topic has been - in close collaboration with Jovica Ninkovic - the role of RBPs in neurogenesis in the dentate gyrus and in reprograming of astrocytes to primary neurons.

Below is a brief summary of current research projects being conducted in the lab.

1. Investigating the dynamics of the neuronal RNP network (funded by the DFG, KI 502/9-1)

In this project, we want to study RNP assembly in primary neurons and unravel the underlying dynamics of the RNP network. Therefore, we will exploit a battery of interactor screens complemented with live-cell imaging and state-of-the-art biochemistry to unravel how the RBP network dynamically assembles and balances cellular alterations. Read more...

2. Pumilio2-mediated control of local protein expression in neurons

We have extensively characterized the RBP Pum2 in primary neurons including its neuronal targets (Vessey et al., 2006, 2010, 2012, Schieweck et al., 2021). Of particular interest is the fact that Pum2 regulates the expression of several key components of the GABA pathway. Therefore, not surprisingly, Pum2 deficiency has been linked to epilepsy, a neurological disease characterized by neuronal hyperexcitability, in mice (Follwaczny et al., 2017, DMM) and humans (XL Wu et al., 2015, Epilepsy & Behavior). In this project, we would like to unravel how the RBP Pum2 represses neuronal targets at the synapse and how this yields epileptic seizures in adult mice.

3. The role of translation in shaping microglial activation states during neuroinflammation (funded by the DFG, SPP2395, KI 502/12-1)

In this newly funded project together with Max Harner, a close collaboration with Jovica Ninkovic, we are studying how specific changes in translation drive microglial reactivity. In particular, we propose the following experimental aims:

• Establish the causal relationship between microglial activation and translation rate regulation
• Determine if global or selective translation changes drive microglial reactivity
• Uncover the mechanisms regulating translation during the transition from homeostatic to reactive microglia states

4. The role of the RNA-binding protein Pum2 in lineage choice of adult neural stem cells and its impact on neuronal differentiation

In this long-term project, another close collaboration with Jovica Ninkovic and Gregor Pilz, we are unraveling the role of the RBP Pum2 in cell fate determination of neural stem cells (NSCs). By focusing on neurogenesis in the DG of the adult hippocampus, one of the important stem cell niches in the mammalian brain, we are investigating how Pum2 determines neuronal differentiation and what consequences arise in vivo in the absence of Pum2 for the function of the hippocampus.
Our pilot experiments provide significant support for this hypothesis: (i) Pum2 controls cell fate decision in the DG of Pum2 GT and adult WT animals; (ii) its absence results in the accumulation of a novel cell type (TSCs) that is clearly distinct from glial and neuronal cells; (iii) these cells can be identified upon downregulation of Pum2 but also (to a much lesser extent) in WT animals. These findings led us to set up a working model in which the translational regulator Pum2 (Vessey et al. 2006, Schieweck et al. 2021b) controls first whether differentiating cells enter regular indirect or direct neurogenesis, and second the transition of RGCs to neurons via a transient state in the latter pathway.

Team