Biology subjects

Alamban, A.

Publications and source records attributed to Alamban, A..

3 recordsLinked to original sources

bioRxiv2026

Self-reinforcing ROS-aneuploidy feedback loop shapes preimplantation development

Aneuploidy and oxidative stress have each been implicated in impaired embryonic development, yet their relationship remains unclear. Here we discover a self-reinforcing ROS-aneuploidy feedback loop with hysteretic properties in preimplantation development. In human blastocysts, oxidative stress associates with aneuploidy at the population level. Paradoxically, euploid and aneuploid embryos can show overlapping oxidative states, and oxidative stress is uncoupled from morphological, temporal, and maternal age-associated indicators of developmental competence. To test whether oxidative stress and aneuploidy merely co-occur or actively influence one another, we used IVF-derived mouse embryos. Induced chromosome missegregation elevates oxidative damage, while oxidative perturbations promote aneuploidy. Crucially, restoring ROS to baseline levels fails to rescue chromosome integrity or developmental potential, revealing hysteresis whereby outcomes depend more on prior chromosomal history than on instantaneous redox state. Together, these reveal that transient redox perturbations can induce persistent chromosomal alterations that shape developmental outcomes even after redox balance is restored, thereby challenging proposals of ROS as a biomarker of embryonic competence.

developmental biology↗

bioRxiv2022

Cytoplasmic divisions without nuclei

Cytoplasmic divisions have been commonly considered a sequel to nuclear divisions, even in the absence of DNA replication. Here we found in fruit fly embryos that the cytoplasm can compartmentalize and divide without nuclei. Our targeted screen for potential necessary and sufficient conditions revealed that, although the cytoplasmic compartments are tightly associated with centrosomes, they can form without astral microtubules and divide without centrioles. Although a focal pool of microtubules is necessary for maintaining cytoplasmic compartments, this is not sufficient for their initial formation. Actin filaments are similarly an essential component of cytoplasmic compartments; however, their myosin II-based contractility is unexpectedly dispensable for divisions. We show that the myosin II-based contractility is instead involved in regulating the pace of these divisions. Importantly, our results revealed that the cytoplasmic divisions without nuclei can occur in a periodic manner autonomously of the Cdk-Cyclin oscillator that normally drives the cell cycle. We demonstrate that such autonomy of cytoplasmic divisions is preserved even in normal development, where it is leveraged to extrude mitotically delayed nuclei from the blastoderm, protecting the synchrony of rapid nuclear divisions against local delays in mitotic entry. We propose that an active coordination between otherwise autonomous cycles of cytoplasmic and nuclear divisions acts as a quality control mechanism for genome integrity and partitioning in development.

cell biology↗

bioRxiv2021

Endoplasmic reticulum stress activates human IRE1α through reversible assembly of inactive dimers into small oligomers

Protein folding homeostasis in the endoplasmic reticulum (ER) is regulated by a signaling network, termed the unfolded protein response (UPR). Inositol-requiring enzyme 1 (IRE1) is an ER membrane-resident kinase/RNase that mediates signal transmission in the most evolutionarily conserved branch of the UPR. Dimerization and/or higher-order oligomerization of IRE1 are thought to be important for its activation mechanism, yet the actual oligomeric states of inactive, active, and attenuated mammalian IRE1 complexes remained unknown. We developed an automated two-color single-molecule tracking approach to dissect the oligomerization of tagged endogenous human IRE1 in live cells. In contrast to previous models, our data indicate that IRE1 exists as a constitutive homodimer at baseline and assembles into small oligomers upon ER stress. We demonstrate that the formation of inactive dimers and stress-dependent oligomers is fully governed by IRE1s lumenal domain. Phosphorylation of IRE1s kinase domain occurs more slowly than oligomerization and is retained after oligomers disassemble back into dimers. Our findings suggest that assembly of IRE1 dimers into larger oligomers specifically enables trans- autophosphorylation, which in turn drives IRE1s RNase activity.

biophysics↗