Biology subjects

Nguyen, L. T.

Publications and source records attributed to Nguyen, L. T..

3 recordsLinked to original sources

bioRxiv2018

Simulations suggest a constrictive force is required for Gram-negative bacterial cell division

To divide, Gram-negative bacterial cells must remodel their peptidoglycan cell wall to a smaller and smaller radius at the division site, but how this process occurs remains debated. While the tubulin homolog FtsZ is thought to generate a constrictive force, it has also been proposed that cell wall remodeling alone is sufficient to drive membrane constriction, possibly via a make-before-break mechanism in which new hoops of cell wall are made inside the existing hoops (make) before bonds in the existing wall are cleaved (break). Previously, we constructed software, REMODELER 1, to simulate cell wall remodeling in rod-shaped bacteria during growth. Here, we used this software as the basis for an expanded simulation system, REMODELER 2, which we used to explore different mechanistic models of cell wall division. We found that simply organizing the cell wall synthesis complexes at the midcell was not sufficient to cause wall invagination, even with the implementation of a make-before-break mechanism. Applying a constrictive force at the midcell could drive division if the force was sufficiently large to initially constrict the midcell into a compressed state before new hoops of relaxed cell wall were incorporated between existing hoops. Adding a make-before-break mechanism could drive division with a smaller constrictive force sufficient to bring the midcell peptidoglycan into a relaxed, but not necessarily compressed, state.

biophysics↗

bioRxiv2017

Structure of the fission yeast actomyosin ring during constriction

Cell division in many eukaryotes is driven by a ring containing actin and myosin. While much is known about the main proteins involved, the precise arrangement of actin filaments within the contractile machinery, and how force is transmitted to the membrane remains unclear. Here we use cryosectioning and cryo-focused ion beam milling to gain access to cryo-preserved actomyosin rings in Schizosaccharomyces pombe for direct three-dimensional imaging by electron cryotomography. Our results show that straight, overlapping actin filaments, running nearly parallel to each other and to the membrane, form a loose bundle of approximately 150 nm in diameter that \"saddles\" the inward-bending membrane at the leading edge of the division septum. The filaments do not make direct contact with the membrane. Our analysis of the actin filaments reveals the variability in filament number, nearest-neighbor distances between filaments within the bundle, their distance from the membrane and angular distribution with respect to the membrane.\n\nSignificance StatementMost eukaryotic cells divide using a contractile actomyosin ring, but its structure is unknown. Here we use new specimen preparation methods and electron cryotomography to image constricting rings directly in 3D, in a near-native state in the model organism Schizosaccharomyces pombe. Our images reveal the arrangement of individual actin filaments within the contracting actomyosin ring.

cell biology↗

bioRxiv2017

Complex models of sequence evolution require accurate estimators as exemplified with the invariable site plus Gamma model

The invariable site plus {Gamma} model is widely used to model rate heterogeneity among alignment sites in maximum likelihood and Bayesian phylogenetic analyses. The proof that the invariable site plus continuous {Gamma} model is identifiable (model parameters can be inferred correctly given enough data) has increased the creditability of its application to phylogeny reconstruction. However, most phylogenetic software implement the invariable site plus discrete {Gamma} model, whose identifiability is likely but unproven. How well the parameters of the invariable site plus discrete {Gamma} model are estimated is still disputed. Especially the correlation of the fraction of invariable sites with the fractions of sites with a slow evolutionary rate is discussed as being problematic. We show that optimization heuristics as implemented in frequently used phylogenetic software cannot always reliably estimate the shape parameter, the proportion of invariable sites and the tree length. Here, we propose an improved optimization heuristic that accurately estimates the three parameters. While research efforts mainly focus on tree search methods, our results signify the equal importance of verifying and developing effective estimation methods for complex models of sequence evolution.

evolutionary biology↗