Biology subjects

Wilke, N.

Publications and source records attributed to Wilke, N..

3 recordsLinked to original sources

bioRxiv2026

Local translation drives glioblastoma heterogeneity and tumor invasion

O_FIG O_LINKSMALLFIG WIDTH=174 HEIGHT=200 SRC="FIGDIR/small/722387v1_ufig1.gif" ALT="Figure 1"> View larger version (96K): org.highwire.dtl.DTLVardef@1da020corg.highwire.dtl.DTLVardef@1bc9b32org.highwire.dtl.DTLVardef@171198aorg.highwire.dtl.DTLVardef@43ce6f_HPS_FORMAT_FIGEXP M_FIG C_FIG Glioblastoma is characterized by diffuse brain invasion, yet the subcellular mechanisms enabling this aggressive behavior remain poorly understood. A subpopulation of glioblastoma cells forms invasive tumor microtubes (TMs), neurite-like extensions that drive whole-brain colonization. Here, we establish local protein translation as a fundamental driver of TM dynamics and invasive cell states. Developing a subcellular transcriptomics approach - integrating subcellular organelle organization with spatially resolved transcriptomics and functional readouts - we reveal that TM gene expression drives cell state identity. Invasive cells further exhibit significantly elevated local translation in protruding TMs, directly linking subcellular protein synthesis to functional invasive states associated with neurodevelopmental programs of axonal growth cones. Targeted disruption of TM-localized translation via photoswitchable puromycin, and specific knockdowns of the TM-enriched proteins GPM6A and GAP43, impaired TM dynamics, suppressed invasion, and reduced tumor growth. Together, these findings define local translation as a key determinant of tumor heterogeneity and glioblastoma invasion.

cancer biology↗

bioRxiv2026

Ursolic Acid Inhibits Rotavirus Replication Through Modulation Of Lipid Droplet Homeostasis

Rotavirus (RV) replication occurs within viroplasms (VP), which are globular, membrane-less cytosolic inclusions primarily assembled by the viral NSP5 and NSP2 proteins. Among host factors, lipid droplets (LD) are strictly required for VP biogenesis. LD are ubiquitous organelles consisting of a neutral lipid core surrounded by a phospholipid monolayer and associated proteins. Ursolic acid (UA), a pentacyclic triterpenoid widely present in plants and fruits, displays multiple biological activities, including modulation of lipid metabolism, and exhibits antiviral activity against RV, as we have previously demonstrated. Here, we investigated the molecular mechanism underlying the antiviral effect of UA. Using biophysical approaches, we first examined the impact of UA on LD formation, finding that it impairs LD biogenesis, consistent with reduced LD budding from the endoplasmic reticulum. We then employed cell-based assays to assess LD turnover and observed that UA acts as a lipolytic stimulus, leading to a marked reduction in LD abundance. Notably, we found that autophagic pathways contribute to LD degradation in the presence of UA. Finally, molecular dynamics simulations proposed that UA, owing to its intrinsic lipid-partitioning capacity, inserts into the LD phospholipid monolayer, establishing interactions with interdigitated neutral lipids. Together, our results indicate that UA both hampers LD biogenesis and accelerates LD degradation, likely through its association with and destabilization of the LD membrane. This dual effect leads to LD depletion, thereby impairing VP formation and ultimately inhibiting RV replication. IMPORTANCEDiarrheal diseases caused by a wide range of pathogens, including bacteria and viruses, remain a major global public health concern, accounting for more than one million deaths annually. These diseases mainly affect children under five years of age, with RV being the primary cause of diarrheal mortality in this age group. The burden is particularly severe in low- and middle-income countries. To address RV-associated disease, coordinated public health interventions have been implemented worldwide, including improvements in water, sanitation, hygiene, the introduction of vaccines, and the widespread use of oral rehydration therapy. Although these measures have substantially reduced the global burden of diarrheal diseases, the lack of a specific antiviral treatment against RV highlights the need for continued research. The development of antiviral strategies could provide a valuable complementary approach to existing interventions and help further reduce morbidity and mortality in infected children.

microbiology↗

bioRxiv2020

Regulation of the activity of an antimicrobial peptide by sterols or hopanoids: possible role in cell recognition

It is now accepted that hopanoids act as sterol-surrogates in membranes of some sterol-lacking bacteria. Here we inquiry whether the hopanoid diplopterol (DP) could attenuate the activity of the antimicrobial peptide Polybia-MP1 (MP1) similarly to cholesterol (CHO). Survival of P. aeruginosa exposed to MP1 was lower for cells incubated with DP than those incubated with CHO, and the affinity and subsequent effect of the peptide on lipid bilayers were different in the presence of DP than in the presence of CHO. Membrane properties showed a non-monotonic behavior as the peptide adsorbed, penetrated, and translocated bilayers with DP suggesting a reorganization of MP1 during these processes. We conclude that MP1 selectivity is finely tuned by lipid composition, and propose the differential interaction and consequent effect promoted by the peptide in membranes with diplopterol as a promising starting point for targeting antimicrobial peptides to hopanoid-containing bacterial membranes.

biophysics↗