News | IMPRS for Molecules of Life

Publication of IMPRS-LS student Stefan Bauernfried

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Bauernfried, S., and Hornung, V.
J Exp Med, 2022, 219, online ahead of print.
DOI: 10.1084/jem.20211405

Human NLRP1: From the shadows to center stage

In response to infection or cell damage, inflammasomes form intracellular multimeric protein complexes that play an essential role in host defense. Activation results in the maturation and subsequent secretion of pro-inflammatory cytokines of the IL-1 family and a specific cell death coined pyroptosis. Human NLRP1 was the first inflammasome-forming sensor identified at the beginning of the millennium. However, its functional relevance and its mechanism of activation have remained obscure for many years. Recent discoveries in the NLRP1 field have propelled our understanding of the functional relevance and molecular mode of action of this unique inflammasome sensor, which we will discuss in this perspective.

Publication of IMPRS-LS student Beatrice Laudenbach

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Laudenbach, B.T., Krey, K., Emslander, Q., Andersen, L.L., Reim, A., Scaturro, P., Mundigl, S., Dächert, C., Manske, K., Moser, M., Ludwig, J., Wohlleber, D., Kröger, A., Binder, M., and Pichlmair, A.
(IMPRS-LS students are in bold)
Nat Commun, 2021, 12, 6918
DOI: 10.1038/s41467-021-27239-y

NUDT2 initiates viral RNA degradation by removal of 5'-phosphates

While viral replication processes are largely understood, comparably little is known on cellular mechanisms degrading viral RNA. Some viral RNAs bear a 5'-triphosphate (PPP-) group that impairs degradation by the canonical 5'-3' degradation pathway. Here we show that the Nudix hydrolase 2 (NUDT2) trims viral PPP-RNA into monophosphorylated (P)-RNA, which serves as a substrate for the 5'-3' exonuclease XRN1. NUDT2 removes 5'-phosphates from PPP-RNA in an RNA sequence- and overhang-independent manner and its ablation in cells increases growth of PPP-RNA viruses, suggesting an involvement in antiviral immunity. NUDT2 is highly homologous to bacterial RNA pyrophosphatase H (RppH), a protein involved in the metabolism of bacterial mRNA, which is 5'-tri- or diphosphorylated. Our results show a conserved function between bacterial RppH and mammalian NUDT2, indicating that the function may have adapted from a protein responsible for RNA turnover in bacteria into a protein involved in the immune defense in mammals.

Publication of IMPRS-LS student Yusuf Qutbuddin

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Qutbuddin, Y., Krohn, J.H., Brüggenthies, G.A., Stein, J., Gavrilovic, S., Stehr, F., and Schwille, P.
(IMPRS-LS students are in bold)
J Phys Chem B, 2021, 125, 13181-13191
DOI: 10.1021/acs.jpcb.1c07694

Design Features to Accelerate the Higher-Order Assembly of DNA Origami on Membranes

Nanotechnology often exploits DNA origami nanostructures assembled into even larger superstructures up to micrometer sizes with nanometer shape precision. However, large-scale assembly of such structures is very time-consuming. Here, we investigated the efficiency of superstructure assembly on surfaces using indirect cross-linking through low-complexity connector strands binding staple strand extensions, instead of connector strands binding to scaffold loops. Using single-molecule imaging techniques, including fluorescence microscopy and atomic force microscopy, we show that low sequence complexity connector strands allow formation of DNA origami superstructures on lipid membranes, with an order-of-magnitude enhancement in the assembly speed of superstructures. A number of effects, including suppression of DNA hairpin formation, high local effective binding site concentration, and multivalency are proposed to contribute to the acceleration. Thus, the use of low-complexity sequences for DNA origami higher-order assembly offers a very simple but efficient way of improving throughput in DNA origami design.

Graduation of Rohit Agarwal

Congratulations on your PhD!

Rohit Agarwal

Ultra-high Throughput Studies of Rare Events and Multi-molecular Complexes using Flow Magnetic Tweezers

RG: Karl Duderstadt

Graduation of Derya Kabacaoğlu

Congratulations on your PhD!

Derya Kabacaoğlu

Understanding the function of NF-κB transcription factor c-Rel in pancreatic cancer

RG: Hana Algül

Publication of IMPRS-LS student Jose Maria Martinez de Paz

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Martinez de Paz, J.M., and Macé, E.
Neuroimage, 2021, 245, 118722.
DOI: 10.1016/j.neuroimage.2021.118722

Functional ultrasound imaging: A useful tool for functional connectomics?

Functional ultrasound (fUS) is a hemodynamic-based functional neuroimaging technique, primarily used in animal models, that combines a high spatiotemporal resolution, a large field of view, and compatibility with behavior. These assets make fUS especially suited to interrogating brain activity at the systems level. In this review, we describe the technical capabilities offered by fUS and discuss how this technique can contribute to the field of functional connectomics. First, fUS can be used to study intrinsic functional connectivity, namely patterns of correlated activity between brain regions. In this area, fUS has made the most impact by following connectivity changes in disease models, across behavioral states, or dynamically. Second, fUS can also be used to map brain-wide pathways associated with an external event. For example, fUS has helped obtain finer descriptions of several sensory systems, and uncover new pathways implicated in specific behaviors. Additionally, combining fUS with direct circuit manipulations such as optogenetics is an attractive way to map the brain-wide connections of defined neuronal populations. Finally, technological improvements and the application of new analytical tools promise to boost fUS capabilities. As brain coverage and the range of behavioral contexts that can be addressed with fUS keep on increasing, we believe that fUS-guided connectomics will only expand in the future. In this regard, we consider the incorporation of fUS into multimodal studies combining diverse techniques and behavioral tasks to be the most promising research avenue.

Publication of IMPRS-LS student Jonathan Schwach

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Schwach, J., Kolobynina, K., Brandstetter, K., Gerlach, M., Ochtrop, P., Helma, J., Hackenberger, C.P.R., Harz, H., Cardoso, M.C., Leonhardt, H., and Stengl, A.
(IMPRS-LS students are in bold)
Chembiochem, 2021, 22, 1205-1209
DOI: 10.1002/cbic.202000727

Site-Specific Antibody Fragment Conjugates for Reversible Staining in Fluorescence Microscopy

Antibody conjugates have taken a great leap forward as tools in basic and applied molecular life sciences that was enabled by the development of chemoselective reactions for the site-specific modification of proteins. Antibody-oligonucleotide conjugates combine the antibody's target specificity with the reversible, sequence-encoded binding properties of oligonucleotides like DNAs or peptide nucleic acids (PNAs), allowing sequential imaging of large numbers of targets in a single specimen. In this report, we use the Tub-tag® technology in combination with Cu-catalyzed azide-alkyne cycloaddition for the site-specific conjugation of single DNA and PNA strands to an eGFP-binding nanobody. We show binding of the conjugate to recombinant eGFP and subsequent sequence-specific annealing of fluorescently labelled imager strands. Furthermore, we reversibly stain eGFP-tagged proteins in human cells, thus demonstrating the suitability of our conjugation strategy to generate antibody-oligonucleotides for reversible immunofluorescence imaging.

Graduation of Johanna Tüshaus

Congratulations on your PhD!

Johanna Tüshaus

Proteomic secretome analysis of primary brain cells

RG: Stefan Lichtenthaler

Graduation of Giulia Chiapparini

Congratulations on your PhD!

Giulia Chiapparini

Structural and Biochemical Characterisation of Minimal Translesion Synthesis Complexes

RG: Christian Biertümpfel

Danny Nedialkova selected as EMBO Young Investigator

Danny Nedialkova, head of the Max Planck Research Group "Mechanisms of Protein Biogenesis" at the Max Planck Institute (MPI) of Biochemistry, has been elected into the EMBO Young Investigator Network. As one of 26 life science researchers chosen this year, she will receive financial support and access to a range of mentoring and training programs for a period of four years, starting in January 2022. "It’s an honor and a privilege to join the Young Investigator network, and I am excited about the new possibilities this opens up for me and my team," says Danny Nedialkova.

“They have already demonstrated scientific excellence despite only recently launching their own laboratories. The EMBO Young Investigator Programme will aid them in taking their career to the next level. We look forward to supporting them during an important phase of their career.” says Michael N. Hall, EMBO Director ad interim. For the synthesis of proteins, the sequence of nucleic acids, the basic building blocks of genetic information, is translated into a specific sequence of amino acids, the basic building blocks of proteins. This is called the genetic code. Danny Nedialkova’s research explores how the genetic code is translated into the thousands of different proteins that make up each cell. Her team uses genome-wide approaches and functional genomics to investigate how protein synthesis is regulated during development and in different cell types.