Ubiquitin-fold modifier 1 (UFM1) is a ubiquitin-like protein (UBL) covalently attached to substrates through a dedicated enzymatic cascade (UFMylation) and removed by specific proteases. Despite a key role in endoplasmic reticulum (ER)-ribosome homeostasis, the basis by which this UBL supports cell fitness remains elusive, as the essentiality of UFMylation machinery varies widely across hundreds of […]

Hypoxia-inducible factors (HIFs) are key regulators of cellular responses to low oxygen (hypoxia), controlling the expression of genes required for survival and adaptation. KDM2B, a chromatin-modifying enzyme, is a direct target of HIF-1, but its precise role in regulating HIF and the hypoxia response remains unclear. Here, we investigated the role of KDM2B in the […]

During neurogenesis, neuroblasts are selected from proneural-competent cells through lateral inhibition, a process controlled by the evolutionarily conserved Notch signalling pathway. By tracking transcription from Notch-target genes and cell morphologies in real time, we discovered that the presumptive neuroblast never initiates target-gene transcription. This implies a pre-existing bias directs Notch signalling. The bias correlates with […]

Thylakoid membranes are indispensable for oxygenic photosynthesis, yet the mechanisms that protect these membranes from photooxidative damage remain poorly understood. By screening previously uncharacterized proteins induced during the chloroplast unfolded protein response, we identify VIA1 as an essential factor for preserving thylakoid integrity under high light in the model green alga Chlamydomonas reinhardtii. Loss of […]

We discovered that palmatine (PAL), a well-known natural product, was inducing the fluorogenic fixation of live cells upon visible light irradiation. This ultrafast phenomenon proceeded under high spatiotemporal control down to single cells (SC), with persistence of well-preserved fixed-labeled cells. Cell optofixing was mediated by PAL interaction with nuclear and mitochondrial DNA, yielding reactive oxygen […]

Kinesin motors drive long-range intracellular transport through coordinated cargo recognition and conformational autoregulation, yet the mechanisms that selectively control cargo engagement remain unclear. Here, we identify a phosphorylation-dependent gate on kinesin-1 activity mediated by the carboxy-terminal domain (CTD) of kinesin light chain 2 (KLC2). The KLC2 CTD is constitutively phosphorylated on multiple serine residues, suppressing […]

Individual cells exhibit distinct molecular landscapes shaped by proteins and the diverse functional repertoire of their corresponding proteoforms. These structurally diverse variants (e.g., post-translationally modified including truncated proteolyzed forms) collectively orchestrate cellular functions. However, resolving proteoform heterogeneity at single-cell (SC) resolution remains a significant analytical challenge. Here, we present a shotgun SC top-down proteomics (SC-TDP) […]

Asymmetric self-organization is a hallmark of cell polarity, yet the diversity of observed polarization patterns is frequently attributed to specialized, complex biochemical mechanisms motifs beyond simple positive feedback. Here, we demonstrate that spatial heterogeneity alone fundamentally reshapes polarization dynamics within minimal stochastic reaction-diffusion processes. We show that weak differences in reaction rates between distinct spatial […]

Long noncoding RNAs (LncRNAs) have emerged as a class of important regulatory ncRNAs and are known to fine- tune numerous cellular processes including proliferation, differentiation and development; however, their role in quiescence still remains largely unexplored. A miRNA host gene lncRNA, MIR503HG, has been reported to play important role in cancer development. Here, we demonstrate […]

Variants in TMEM106B and GRN, which encode lysosomal proteins, interact through unknown mechanisms to increase the risk of age-related cognitive decline and neurodegeneration. Here, we show that these variants converge on a single molecular intermediate: the cleaved intra-lysosomal fibril core of TMEM106B, a precursor to amyloid fibrils that accumulate in the aging brain. A protein-coding […]

Caveolae, flask-shaped membrane invaginations highly enriched in endothelial cells, play a central role in buffering membrane tension, yet the principles governing their spatial organization remain elusive. This investigation sought to generate the most comprehensive and systematic analysis of blood vessel caveolar spatial organization. To do so, our group leveraged micropatterning technologies to impose precise biophysical […]

Intracerebral haemorrhage (ICH) is a severe form of stroke with high morbidity and mortality rates. For survivors, acute haematoma expansion strongly determines neurological outcome. Although blood pressure reduction is widely investigated as a strategy to limit haematoma growth, the haemodynamic mechanisms regulating haemorrhage development remain poorly understood. Zebrafish provide a tractable in vivo model to […]