Where in a nerve cell is a certain receptor protein located? Without an answer to this question, it is difficult to draw firm conclusions about the function of this protein. Two scientists at the Max Planck Institute of Neurobiology developed a method in the fruit fly that marks receptor proteins in selected cells. In this way, they gained new insights into the neuronal mechanisms of motion vision. In addition, the research community receives an innovative tool to label proteins of all kinds.

One of the most fundamental questions in neurobiology is how sensory inputs are processed within the neuronal circuits of the brain. Thereby, it is not only important to understand which neurons are connected via synapses, but also how they communicate with each other. Receptors play a decisive role in this process.

These special proteins sit in the membrane envelope of neurons and specifically at synapses, where they receive incoming signals from other cells. Depending on receptor type and position, they determine how the cells react to incoming information: are they activated or inhibited, and how quickly does this happen? To understand a neural network in its entirety, it is therefore essential to study receptors and their distribution in neurons. However, this is not an easy task.

Some established methods provide little or no information about the distribution of proteins. Other techniques allow the labelling of receptors artificially introduced into cells, but not of naturally occurring ones. Therefore, the PhD students Sandra Fendl and Renee Vieira from Alexander Borst's department used the genetic resources available in the fruit fly Drosophila and developed a method to label proteins.

Read more



A team of scientists from the Neuro-Electronics Research Flanders developed and tested, in cooperation with scientists from the MPI of Neurobiology, a new volumetric functional ultrasound imaging platform. The ease of use, reliability, and affordability of the technology make it an excellent candidate for driving future brain-wide neuroimaging research.

Ultrasound is used to image soft tissue or organs, such as the heart, lungs and bladder, in real time. It is routinely used in hospitals because it is both safe and affordable. Over the past ten years, scientists at the Urban Lab (NERF, empowered by imec, KU Leuven and VIB) have contributed to the development of innovative brain ultrasound hardware and software solutions in collaboration with several academic and industrial partners. Using functional ultrasound imaging (fUSI) they have succeeded to visualize neural activity by mapping local changes in cerebral blood flow. Initially, however, fUSI was restricted to cross-sectional 2D imaging within a small field of view, which meant that visualization of brain-wide activity remained a challenge.

Read more



Spotting, pursuing and catching prey – for many animals this is an essential task for survival. Scientists at the Max Planck Institute of Neurobiology now show in zebrafish that the localization of neurons in the midbrain is adapted to a successful hunting sequence.

Far away, in the periphery of its visual field, a tiny zebrafish larva detects a small dot moving sideways. Is it prey or is it a threat, for instance, a distant predator sneaking up on it? Within the shortest possible time, the fish decides that it must be potential prey. The larva turns toward the object, approaches it, until it is right in front, and snaps shut – one of its daily hunting routines is successfully finished.

What might sound straightforward, is actually a highly complex process. Many different visual stimuli are detected simultaneously, transferred from the eye to the brain, and further processed. Interestingly, the stimuli don’t reach the brain at random locations: every position on the retina is transmitted to a very specific location in the tectum of the midbrain, the processing hub for visual stimuli. However, apart from that, there is not much knowledge of how the neurons are wired and organized, or which signals they specifically react to. Dominique Förster and a team from Herwig Baier’s laboratory analyzed how retinal ganglion cells transfer visual information from the eye to the tectum and how this input is further processed.

Read more



Publication Placeholder

Weng, T.H., Steinchen, W., Beatrix, B., Berninghausen, O., Becker, T., Bange, G., Cheng, J., and Beckmann, R.
EMBO J, 2020, e105643, online ahead of print.
doi: 10.15252/embj.2020105643

Architecture of the active post-translational Sec translocon

In eukaryotes, most secretory and membrane proteins are targeted by an N-terminal signal sequence to the endoplasmic reticulum, where the trimeric Sec61 complex serves as protein-conducting channel (PCC). In the post-translational mode, fully synthesized proteins are recognized by a specialized channel additionally containing the Sec62, Sec63, Sec71, and Sec72 subunits. Recent structures of this Sec complex in the idle state revealed the overall architecture in a pre-opened state. Here, we present a cryo-EM structure of the yeast Sec complex bound to a substrate, and a crystal structure of the Sec62 cytosolic domain. The signal sequence is inserted into the lateral gate of Sec61α similar to previous structures, yet, with the gate adopting an even more open conformation. The signal sequence is flanked by two Sec62 transmembrane helices, the cytoplasmic N-terminal domain of Sec62 is more rigidly positioned, and the plug domain is relocated. We crystallized the Sec62 domain and mapped its interaction with the C-terminus of Sec63. Together, we obtained a near-complete and integrated model of the active Sec complex.



graduationCongratulations on your PhD!

Iris Martí Fernández

Antibodies to Myelin Oligodendrocyte Glycoprotein (MOG): Analysis of the impact of the glycosylation site of MOG for recognition of human autoantibodies and dissection of effector functions of the anti-MOG monoclonal antibody 8-18C5

RG: Reinhard Hohlfeld



Ralf Jungmann, head of the research group "Molecular Imaging and Bionanotechnology" receives ERC Consolidator Grant

Ralf Jungmann, head of the research group “Molecular Imaging and Bionanotechnology” at the Max Planck Institute of Biochemistry in Martinsried and Professor for Experimental Biophysics at the LMU Munich receives the Consolidator Grant of the European Research Council. It comes with funding of 2.3 million Euros over five years. With his team, Jungmann aims to develop novel imaging technologies to unravel how the nanoscale organization of surface proteins on immune and tumor cells dictates their decision-making processes. The techniques could yield fundamental insights into the molecular architecture of immune cell interactions and enable the future development of more refined “pattern”-based immunotherapeutics. One of the major aims of many therapeutics is targeting cell surface proteins to alter cellular behavior. Recently approved immunotherapeutic drugs trigger anti-tumor immunity by disrupting key cell surface proteins that guide immune cell interactions.

Despite the cell surface representing a major site of drug action, its nanoscale organization remains poorly characterized. “The main reason for this is largely due to technical limitations of fluorescence imaging approaches” says Jungmann. “Current techniques do not allow high-throughput measurements of the spatial localization and interaction of hundreds of proteins with true single-protein-resolution on cell surfaces”, Jungmann continues. With the ERC Consolidator Grant “ReceptorPAINT – Imaging Receptomics as a tool for biomedical discovery”, his research team aims to develop novel imaging technologies based on DNA-PAINT microscopy to enable the visualization and quantification of all relevant cell surface proteins at single-protein-resolution.

Read more



graduationCongratulations on your PhD!


Stephanie Schumacher

Structural and biochemical characterization of the interaction between focal adhesion receptor integrin α5β1 and fibronectin

RG: Naoko Mizuno




Publication Placeholder

Blessing, C., Mandemaker, I.K., Gonzalez-Leal, C., Preisser, J., Schomburg, A., and Ladurner, A.G.
(IMPRS-LS students are in bold)
Mol Cell, 2020, 80, 862-875.e866.
doi: 10.1016/j.molcel.2020.10.009

The Oncogenic Helicase ALC1 Regulates PARP Inhibitor Potency by Trapping PARP2 at DNA Breaks

The anti-tumor potency of poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) has been linked to trapping of PARP1 on damaged chromatin. However, little is known about their impact on PARP2, an isoform with overlapping functions at DNA lesions. Whether the release of PARP1/2 from DNA lesions is actively catalyzed by molecular machines is also not known. We found that PARPis robustly trap PARP2 and that the helicase ALC1 (CHD1L) is strictly required for PARP2 release. Catalytic inactivation of ALC1 quantitatively traps PARP2 but not PARP1. ALC1 manipulation impacts the response to single-strand DNA breaks through PARP2 trapping, potentiates PARPi-induced cancer cell killing, and mediates synthetic lethality upon BRCA deficiency. The chromatin remodeler ALC1 actively drives PARP2 turnover from DNA lesions, and PARP2 contributes to the cellular responses of PARPi. This suggests that disrupting the ATP-fueled remodeling forces of ALC1 might enable therapies that selectively target the DNA repair functions of PARPs in cancer.



Publication Placeholder

Liwocha, J., Krist, D.T., van der Heden van Noort, G.J., Hansen, F.M., Truong, V.H., Karayel, O., Purser, N., Houston, D., Burton, N., Bostock, M.J., Sattler, M., Mann, M., Harrison, J.S., Kleiger, G., Ovaa, H., and Schulman, B.A.
(IMPRS-LS students are in bold)
Nat Chem Biol, 2020, online ahead of print.
doi: 10.1038/s41589-020-00696-0

Linkage-specific ubiquitin chain formation depends on a lysine hydrocarbon ruler

Virtually all aspects of cell biology are regulated by a ubiquitin code where distinct ubiquitin chain architectures guide the binding events and itineraries of modified substrates. Various combinations of E2 and E3 enzymes accomplish chain formation by forging isopeptide bonds between the C terminus of their transiently linked donor ubiquitin and a specific nucleophilic amino acid on the acceptor ubiquitin, yet it is unknown whether the fundamental feature of most acceptors-the lysine side chain-affects catalysis. Here, use of synthetic ubiquitins with non-natural acceptor site replacements reveals that the aliphatic side chain specifying reactive amine geometry is a determinant of the ubiquitin code, through unanticipated and complex reliance of many distinct ubiquitin-carrying enzymes on a canonical acceptor lysine.



Publication Placeholder

Karayel, O., Michaelis, A.C., Mann, M., Schulman, B.A., and Langlois, C.R.
Proc Natl Acad Sci U S A, 2020, online ahead of print.
doi: 10.1073/pnas.2020197117

DIA-based systems biology approach unveils E3 ubiquitin ligase-dependent responses to a metabolic shift

The yeast Saccharomyces cerevisiae is a powerful model system for systems-wide biology screens and large-scale proteomics methods. Nearly complete proteomics coverage has been achieved owing to advances in mass spectrometry. However, it remains challenging to scale this technology for rapid and high-throughput analysis of the yeast proteome to investigate biological pathways on a global scale. Here we describe a systems biology workflow employing plate-based sample preparation and rapid, single-run, data-independent mass spectrometry analysis (DIA). Our approach is straightforward, easy to implement, and enables quantitative profiling and comparisons of hundreds of nearly complete yeast proteomes in only a few days. We evaluate its capability by characterizing changes in the yeast proteome in response to environmental perturbations, identifying distinct responses to each of them and providing a comprehensive resource of these responses. Apart from rapidly recapitulating previously observed responses, we characterized carbon source-dependent regulation of the GID E3 ligase, an important regulator of cellular metabolism during the switch between gluconeogenic and glycolytic growth conditions. This unveiled regulatory targets of the GID ligase during a metabolic switch. Our comprehensive yeast system readout pinpointed effects of a single deletion or point mutation in the GID complex on the global proteome, allowing the identification and validation of targets of the GID E3 ligase. Moreover, this approach allowed the identification of targets from multiple cellular pathways that display distinct patterns of regulation. Although developed in yeast, rapid whole-proteome-based readouts can serve as comprehensive systems-level assays in all cellular systems.