Our Recent Work

Discover the latest work from our doctoral researchers! In this section, our students present their publications along with visuals that highlight their findings. For a full list of publications, visit the Publications tab in the main menu.

Mycoplasma pneumoniae

Serena Arghittu

Research Group: Roberto Covino

Institution: Frankfurt Institute of Advanced Studies

DOI: doi.org/10.1126/sciadv.ady4746

Multicolored protein shaking during computational simulation. — **Spontaneous lipid uptake by P116: first, the lipid splays, then it is transferred into the cavity.** Sina Manger & Serena M Arghittu et al. *Sci. Adv*.(2025).

**Spontaneous lipid uptake by P116: first, the lipid splays, then it is transferred into the cavity.** Sina Manger & Serena M Arghittu et al. *Sci. Adv*.(2025).

Mycoplasma pneumoniae is one of the smallest known bacteria and lacks the metabolic pathways necessary to synthesize many essential lipids for its survival. To compensate for this deficiency, it scavenges lipids directly from the host membranes. A critical player in this process is P116, an essential membrane-anchored protein responsible for lipid uptake and delivery. Our research, which combines molecular dynamics (MD) simulations with fluorescence assays and cryo-electron microscopy, has revealed key steps in the P116 mechanism. Acting as a self-sufficient lipid transporter, P116 interacts with host membranes to extract lipid molecules. It then stores these lipids in two large hydrophobic cavities before releasing them into the bacterial membrane.

The video illustrates a crucial mechanistic step uncovered by our simulations: spontaneous lipid uptake. In this process, a freely diffusing lipid is captured by P116 and guided into its internal cavity without requiring ATP or additional protein partners. This autonomous behavior is due to P116's structural features, including its flexible hinge region, hydrophobic cavity, and specialized access channel, which work together to facilitate efficient lipid capture and translocation. This mechanism demonstrates how a minimal organism like Mycoplasma pneumoniae has evolved an adaptive, energy-independent strategy to secure the membrane components necessary for its survival.

Atlas of the hippocampus

Quinn Waselenchuk

Research Group: Julian Langer / Erin Schuman

Institution: Max Planck Institute of Brain Reseach

DOI: doi.org/10.1038/s41467-025-63119-5

**Fluorescence image of a mouse hippocampal slice. Synapses are shown in green, and blue marks the cell bodies of neurons.** Kaulich et al. *Nature Communications (*2025).

**Fluorescence image of a mouse hippocampal slice. Synapses are shown in green, and blue marks the cell bodies of neurons.** Kaulich et al. *Nature Communications (*2025).

Understanding the complexity of the brain requires detailed maps of both messenger RNAs (mRNAs) and proteins across regions, cell types, and compartments. While recent studies have profiled either transcripts or proteins in specific brain areas, few have systematically integrated both molecular classes across multiple spatial scales in parallel. In this work, we present the first integrated transcriptomic and proteomic atlas of the mouse hippocampus at synaptic resolution. The hippocampus - a region central to learning and memory - was chosen for its well-characterized structure, function, and connectivity. Here, we combined RNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) with precision microdissection of different hippocampal subregions and layers, as well as Fluorescence-Activated Synaptosome Sorting (FASS). This enabled systematic mapping of more than 17,000 mRNAs and 10,000 proteins, uncovering thousands with distinct enrichment patterns, including receptors, ion channels, adhesion molecules, and metabolic regulators. Integration of transcriptome and proteome data highlighted proteins tightly linked to or decoupled from mRNA availability, in part due to protein half-life differences. Incorporation of translatome data then identified roles for protein trafficking versus local translation in establishing compartmental organization of pyramidal neurons, with distal dendrites showing increased reliance on local protein synthesis. Classification of synapses from area CA1 further revealed contributions from kinases, cytoskeletal elements, and adhesion molecules in defining specificity of synapses formed with projections originating from different brain areas. Together, we provide a molecular atlas of the hippocampus and its synapses (accessible at syndive.org) that yields insights into spatial transcript-protein relationships. In doing so, we offer a tool to help the community investigate how molecular organization shapes neuronal and synaptic function.

Protein recruitment

Ainara Claveras

Research Group: Gerhard Hummer

Institution: Max Planck Institute of Biophysics

DOI: 10.1126/science.adl3787

Simulation of the class III phosphatidylinositol (PI) 3-kinase complex 1 as it lies on top of a membrane and phosphorilates its lipids. — **The PI3KC3-C1 complex in the active form stably engaging with the membrane.** Cook, Chen, Nguyen, Claveras et al. *Science* (2025).

**The PI3KC3-C1 complex in the active form stably engaging with the membrane.** Cook, Chen, Nguyen, Claveras et al. *Science* (2025).

To maintain cellular health, our cells get rid of damaged materials, such as protein aggregates, through a process known as autophagy. Thiscomplex process involves a double-membrane organelle called the autophagosome, which engulfs cellular debris and delivers it to the lysosome for degradation. If the autophagy machinery malfunctions, damaged proteins and organelles can accumulate in the cytosol and harm the cell. There is increasing evidence suggesting that defects in autophagy may be linked to neurological diseases like Parkinson’s. One of the first steps of autophagy is to recruit essential proteins to a specific site. The class III phosphatidylinositol (PI) 3-kinase complex 1 (PI3KC3-C1) plays a very important role in this process, as it phosphorylates lipids on the membrane of the autophagosome precursor. These phosphorylated lipids are then recognized by other autophagy proteins. Using a combination of cryo-EM and molecular dynamics simulations, we have obtained valuable insights into the mechanism of activation of the PI3KC3-C1 complex. Our data suggests that the catalytic subunit of the complex needs to reorient before binding to the membrane. Once this subunit engages with the membrane, lipids can access the catalytic site and undergo phosphorylation. We believe our findings will set the stage for future research into the subsequent steps of the autophagy pathway.

Defense against HIV

Jan Philipp Kreysing

Research Group: Martin Beck

Institution: Max Planck Institute of Biophysics

Publication: doi.org/10.1016/j.cell.2024.12.008

The HIV-1 capsid cracks the rings of the nuclear pore complex as it traverses the channel from the cytosol to the nucleus. — **The HIV-1 capsid cracks the rings of the nuclear pore complexas it traverses the channel.** Kreysing, Heidari, Zila et al. *Cell* (2025).

**The HIV-1 capsid cracks the rings of the nuclear pore complexas it traverses the channel.** Kreysing, Heidari, Zila et al. *Cell* (2025).

HIV-1 infection relies on the ability of the virus to transport its genetic material into the nucleus of human cells, where it integrates irreversibly into the host genome. Our work sheds light on the unique mechanism by which the HIV-1 capsid traverses the nuclear pore complex (NPC), a selective barrier guarding the nucleus. Using electron microscopy and computational simulations, we found that the cone-shaped capsid enters the nuclear pore with its narrow end first, exerting mechanical force that cracks the NPC’s ring-shaped structure, allowing the capsid to pass intact into the nucleus. This study further cements the critical role of HIV capsid in the HIV infection process, and introduces the novel concept of nuclear pore complex cracking. Better understanding of how the capsid helps the virus infect our immune cells is vital to developing better drugs against it.

Membrane Remodeling

Borna Markusic

Research Group: Ivan Đikić

Institution: Goethe University Frankfurt

Publication: doi.org/10.1073/pnas.2408071121

Simulation showing an orange lipid membrane being pulled upward by colorful, flexible proteins moving dynamically. The proteins interact with the membrane, creating a bump that deforms its structure. — **The dynamic interaction between the proteins and the membrane leads to structural changes, including deformation.** Poveda-Cuevas et al. *PNAS* (2024).

**The dynamic interaction between the proteins and the membrane leads to structural changes, including deformation.** Poveda-Cuevas et al. *PNAS* (2024).

Until now, the involvement of intrinsic disorder in membrane shaping processes has not been fully understood. A multidisciplinary team around Ramachandra M Bhaskara from Institute of Biochemistry II (IBC2) led by Sergio Alejandro Poveda Cuevas now reports in PNAS detailed insights into how intrinsically disordered regions (IDRs) of membrane proteins remodel cellular membranes. Focusing on the ER-phagy receptor FAM134B, they explored how membrane-anchored disordered regions behave. Through advanced computer modeling and molecular dynamics (MD) simulations, the team found that – depending on context – these highly flexible protein regions exhibit different behaviors: Driven by their conformational entropy alone, they can sense and induce membrane curvature, thereby aiding in local remodeling. However, when combined with membrane-shaping elements like the Reticulon homology domain (RHD), they amplify large-scale remodeling processes by active scaffolding. This Janus-like behavior is sequence-encoded and shared among other proteins involved in ER-phagy. It allows IDRs to boost protein clustering and accelerate the reshaping of the ER, providing a fresh perspective on their role in regulation of membrane dynamics and shaping of cellular organelles.

Structure of NADPH oxidases

Victor Dubach

Research Group: Bonnie Murphy

Institution: Max Planck Institute of Biophysics

Publication: doi.org/10.1038/s41594-024-01348-w

Rotating 3D visualization of the structural map of SpNOX — **3D structure of SpNOX from *Streptococcus pneumoniae*, resolved using cryo-EM.** Dubach et al. *NSMB* (2024).

**3D structure of SpNOX from *Streptococcus pneumoniae*, resolved using cryo-EM.** Dubach et al. *NSMB* (2024).

The NADPH oxidase (NOX) protein family plays an important role in the innate immune system, cell differenation and cancer. The enzyme oxidizes NADPH and use it as an electron source to reduce oxygen on the other side of the membrane. Even though NOXs have been studied for decades, there is little structural and mechanistic information on them. In order to gain insight, we have characterized a bacterial NOX homolog from Streptococcus pneumoniae (SpNOX). In total, four cryo-EM structures were obtained of the 46-kDa SpNOX. These structures were supplemented with targeted mutagenesis based on the obtained structures as well as (an)aerobic activity assays. These data gave insight into the lack of substrate selective of SpNOX opposed to its human homologous as well as the electron pathway across the membrane. Furthermore, the mechanism of the hydride transfer was elucidated allowing us to propose a catalytic cycle for SpNOX and other NOXs.