Excursion of students from the CIPSM graduate educational program to the Bayer AG as part of the lecture series on Innovations Management of Bayer AGs former Board of Management Member Wolfgang Plischke.

Please register here:  postponed indefinitely due to the current situation

|READ MORE|

It’s Christmas and we at CIPSM just wanted to say
Thank you and that it’s been a pleasure working with you this past year.
We wish you and your family wonderful holidays and a Happy New Year!

 

|READ MORE|

RNAs contain post-transcriptional modifications, which fulfill a variety of functions in translation, secondary structure stabilization and cellular stress survival. Here, 2-methylthiocytidine (ms²C) is identified in tRNA of E. coli and P. aeruginosa using NAIL-MS (nucleic acid isotope labeling coupled mass spectrometry) in combination with genetic screening ...

|READ MORE|

TLR8 is among the highest-expressed pattern-recognition receptors in the human myeloid compartment, yet its mode of action is poorly understood. TLR8 engages two distinct ligand binding sites to sense RNA degradation products, although it remains unclear how these ligands are formed in cellulo in the context of complex RNA molecule sensing. Here, we identified ...

|READ MORE|

Sirtuin 5 is a class III histone deacetylase that, unlike its classification, mainly catalyzes desuccinylation and demanoylation reactions. It is an interesting drug target that we use here to test new ideas for calculating reaction pathways of large molecular systems such as enzymes. A major issue with most schemes (e.g., adiabatic mapping) is that the resulting ...

|READ MORE|

Theories about the origin of life require chemical pathways that allow formation of life’s key building blocks under prebiotically plausible conditions. Complex molecules like RNA must have originated from small molecules whose reactivity was guided by physico-chemical processes. RNA is constructed from purine and pyrimidine nucleosides, both of which are ...

|READ MORE|

The Fe(II) and 2-oxoglutarate-dependent oxygenase Alkb homologue 1 (Alkbh1) has been shown to act on a wide range of substrates, like DNA, tRNA and histones. Thereby different enzymatic activities have been identified including, among others, demethylation of N³-methylcytosine (m³C) in RNA- and single-stranded DNA oligonucleotides, demethylation of ...

|READ MORE|

The Scientific Oktoberfest will be this years meeting point for some of the internationally most distinguished researchers in the field of Life Science Chemistry & Biology.

The CIPSM Scientific Oktoberfest will be held from the 19th to the 20th of September at the Institute of Advanced Study IAS in Garching near Munich. At the two-day conference, researchers ...

|READ MORE|

The TATA-binding protein (TBP) and a transcription factor (TF) IIB-like factor compound the fundamental core of all eukaryotic initiation complexes. The reason for the emergence and strict requirement of the additional intiation factor Bdp1, which is unique to the RNA polymerase (RNAP) III sytem, however, remained elusive. A poorly studied aspect in this context ...

|READ MORE|

Psoralens are natural compounds that serve in the light dependent treatment of certain skin diseases (PUVA therapy). They are DNA intercalators that upon photoexcitation form adducts with thymine bases. For one psoralen derivative, 4′-aminomethyl-4,5′,8-trimethylpsoralen (AMT), the photoreactions are characterized here by nanosecond UV–vis and IR absorption ...

|READ MORE|

Lipid droplets (LDs) are ubiquitous organelles comprising a central hub for cellular lipid metabolism and trafficking. This role is tightly associated with their interactions with several cellular organelles. Here, we provide a systematic and quantitative structural description of LDs in their native state in HeLa cells enabled by cellular cryoelectron ...

|READ MORE|

An efficient minimization of the random phase approximation (RPA) energy with respect to the one-particle density matrix in the atomic orbital space is presented. The problem of imposing full self-consistency on functionals depending on the potential itself is bypassed by approximating the RPA Hamiltonian on the basis of the well-known Hartree–Fock Hamiltonian ...

|READ MORE|

Following the discovery of numerous long non-coding RNA (lncRNA) transcripts in the human genome, their important roles in biology and human disease are emerging. Recent progress in experimental methods has enabled the identification of structural features of lncRNAs. However, determining high-resolution structures is challenging as lncRNAs are expected to be ...

|READ MORE|

Assembling composite DNA modules from custom DNA parts has become routine due to recent technological breakthroughs such as Golden Gate modular cloning. Using Golden Gate, one can efficiently assemble custom transcription units and piece units together to generate higher-order assemblies. Although Golden Gate cloning systems have been developed to assemble DNA ...

|READ MORE|

Requirements for novel bioconjugation reactions for the synthesis of Antibody‐Drug‐Conjugates (ADCs) are exceptionally high, since conjugation selectivity as well as stability and hydrophobicity of linkers and payloads drastically influence the performance and safety profile of the final product. Herein we describe Cys‐selective ethynylphosphonamidates as new ...

|READ MORE|

Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm resulting from the malignant transformation of myeloid progenitors. Despite intensive chemotherapy leading to initial treatment responses, relapse caused by intrinsic or acquired drug resistance represents a major challenge. Here, we report that histone 3 lysine 27 demethylase KDM6A (UTX) is ...

|READ MORE|

Affinity maturation of the humoral immune response depends on somatic hypermutation (SHM) of immunoglobulin (Ig) genes, which is initiated by targeted lesion introduction by activation-induced deaminase (AID), followed by error-prone DNA repair. Stringent regulation of this process is essential to prevent genetic instability, but no negative feedback control has ...

|READ MORE|

Tripeptides with two consecutive prolines are the shortest and most frequent sequences causing ribosome stalling. The bacterial translation elongation factor P (EF-P) relieves this arrest, allowing protein biosynthesis to continue. A seven amino acids long loop between beta-strands β3/β4 is crucial for EF-P function and modified at its tip by lysylation of lysine ...

|READ MORE|

Small regulatory RNAs (sRNAs) are crucial components of many stress response systems. The envelope stress response (ESR) of Gram‐negative bacteria is a paradigm for sRNA‐mediated stress management and involves, among other factors, the alternative sigma factor E (σ^E) and one or more sRNAs. In this study, we identified the MicV sRNA as a new member of the σ^E ...

|READ MORE|

Wir freuen uns über ein gelungenes Richtfest des neuen Institutes für Chemische Epigenetik am 13.5.2019 auf dem Campus Großhadern.

Wir danken mit Nachdruck allen Arbeitern, Ingenieuren, Architekten und Planern, die unseren schönen Forschungsbau so schnell und professionell erbaut haben.

Großer Dank gilt Sigrid Bauer für ihre ausgezeichnete Organisation des ...

|READ MORE|

The carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) consists of 26 and 52 heptad-repeats in yeast and mammals, respectively. Studies in yeast showed that the strong periodicity of the YSPTSPS heptads is dispensable for cell growth and that di-heptads interspersed by spacers can act as minimal functional units (MFUs) to fulfil ...

|READ MORE|

Prof. Thomas Carell from CIPSM and Dr. Alexander Karp, founder and CEO of Palantir Technologies (Palo Alto) were elected into the BASF supervisory board (Aufsichtsrat).

|READ MORE|

Histone lysine methylation is generally performed by SET domain methyltransferases and regulates chromatin structure and gene expression. Here, we identify human C21orf127 (HEMK2, N6AMT1, PrmC), a member of the seven-β-strand family of putative methyltransferases, as a novel histone lysine methyltransferase. C21orf127 functions as an obligate heterodimer with ...

|READ MORE|

Bisacylphosphane oxides (BAPOs) are established as photoinitiators for industrial applications. Light irradiation leads to their photolysis, producing radicals. Radical species induce oxidative stress in cells and may cause cell death. Hence, BAPOs may be suitable as photolatent cytotoxic agents, but such applications have not been investigated yet. Herein, we ...

|READ MORE|

A complex relationship exists between environmental factors, signaling networks and phenotypic individuality in bacteria. In this review, we will focus on the organization, function and control points of multiple-input histidine kinase-based signaling cascades as a source of phenotypic heterogeneity. In particular, we will examine the quorum sensing cascade in ...

|READ MORE|

Methanotrophs play a prominent role in the global carbon cycle, by oxidizing the potent greenhouse gas methane to CO₂. Methane is first converted into methanol by methane monooxygenase. This methanol is subsequently oxidized by either a calcium-dependent MxaF-type or a lanthanide-dependent XoxF-type methanol dehydrogenase (MDH). Electrons from methanol oxidation ...

|READ MORE|

We introduce a chemoenzymatic strategy for straightforward in vitro generation of C-terminally linked fusion proteins. Tubulin tyrosine ligase is used for the incorporation of complementary click chemistry handles facilitating subsequent formation of functional bispecific antibody-fragments. This simple strategy may serve as central conjugation hub for a modular ...

|READ MORE|

Metallic nanoparticles were shown to affect Förster energy transfer between fluorophore pairs. However, to date, the net plasmonic effect on FRET is still under dispute, with experiments showing efficiency enhancement and reduction. This controversy is due to the challenges involved in the precise positioning of FRET pairs in the near field of a metallic ...

|READ MORE|

We explore and show the usefulness of the density of states function for computing vibrational free energies and free energy differences between small systems. Therefore, we compare this density of states integration method (DSI) to more established schemes such as Bennett’s Acceptance Ratio method (BAR), the Normal Mode Analysis (NMA), and the Quasiharmonic ...

|READ MORE|

We describe a new technique in protein synthesis that extends the existing repertoire of methods for protein modification: A chemoselective reaction that induces reactivity for a subsequent bioconjugation. Hereby, an azide building block reacts first with an ethynylphosphonite via the Staudinger‐phosphonite reaction (SPhR) to an ethynylphosphonamidate. The ...

|READ MORE|

The free energy is one of the central quantities in material and natural sciences. While being well-established, e.g., in drug design or catalyst optimization, computational methods lack a straightforward way to gain deeper insights into the calculated free energy, and thus the underlying chemical or physical processes. Here, we present a generally applicable, ...

|READ MORE|

A fundamental step in membrane protein biogenesis is their integration into the lipid bilayer with a defined orientation of each transmembrane segment. Despite this, it remains unclear how cells detect and handle failures in this process. Here we show that single point mutations in the membrane protein connexin 32 (Cx32), which cause Charcot-Marie-Tooth disease, ...

|READ MORE|

An ideal point light source is as small and as bright as possible. For fluorescent point light sources, homogeneity of the light sources is important as well as that the fluorescent units inside the light source maintain their photophysical properties, which is compromised by dye aggregation. Here we propose DNA origami as a rigid scaffold to arrange dye ...

|READ MORE|

A common design principle of heteromeric signaling proteins is the use of shared subunits. This allows encoding of complex messages while maintaining evolutionary flexibility. How cells regulate and control assembly of such composite signaling proteins remains an important open question. An example of particular complexity and biological relevance is the ...

|READ MORE|

Escherichia coli and many other bacterial species can enter into a viable but nonculturable (VBNC) state, which is a survival strategy adopted by cells exposed to adverse environmental conditions. Pyruvate is known to be one factor that promotes resuscitation of VBNC cells. Here we studied the role of a pyruvate-sensing network, composed of the histidine ...

|READ MORE|

Bacteria use quorum sensing to monitor cell density and coordinate group behaviours. In Vibrio cholerae, the causative agent of the diarrheal disease cholera, quorum sensing is connected to virulence gene expression via the two autoinducer molecules, AI-2 and CAI-1. Both autoinducers share one signal transduction pathway to control the production of AphA, a key ...

|READ MORE|

All living cells have a large number of proteins that are anchored with one transmembrane helix in the cytoplasmic membrane. Almost nothing is known about their spatiotemporal organization in whole cells. Here we report on the localization and dynamics of one representative, the pH sensor and transcriptional regulator CadC in Escherichia coli. Fluorophore-tagged ...

|READ MORE|

To be able to perform their biological function, a protein needs to be correctly folded into its three dimensional structure. The protein folding process is spontaneous and does not require the input of energy. However, in the crowded cellular environment where there is high risk of inter-molecular interactions that may lead to protein molecules sticking to each ...

|READ MORE|