Biology subjects

Kamnev, A.

Publications and source records attributed to Kamnev, A..

3 recordsLinked to original sources

bioRxiv2021

BioProfiling.jl: Profiling biological perturbations with high-content imaging in single cells and heterogeneous populations

MotivationHigh-content imaging screens provide a cost-effective and scalable way to assess cell states across diverse experimental conditions. The analysis of the acquired microscopy images involves assembling and curating morphological measurements of individual cells into morphological profiles suitable for testing biological hypotheses. Despite being a critical step, there is currently no standard approach to morphological profiling and no solution is available for the high-performance Julia programming language. ResultsHere, we introduce BioProfiling.jl, an efficient end-to-end solution for compiling and filtering informative morphological profiles in Julia. The package contains all the necessary data structures to curate morphological measurements and helper functions to transform, normalize and visualize profiles. Robust statistical distances and permutation tests enable quantification of the significance of the observed changes despite the high fraction of outliers inherent to high-content screens. This package also simplifies visual artifact diagnostics, thus streamlining a bottleneck of morphological analyses. We showcase the features of the package by analyzing a chemical imaging screen, in which the morphological profiles prove to be informative about the compounds mechanisms of action and can be conveniently integrated with the network localization of molecular targets. AvailabilityThe Julia package is available on GitHub: https://github.com/menchelab/BioProfiling.jl We also provide Jupyter notebooks reproducing our analyses: https://github.com/menchelab/BioProfilingNotebooks Contactjoerg.menche@univie.ac.at

bioinformatics↗

bioRxiv2020

Inhibition of cell membrane ingression at the division site by cell wall in fission yeast

Eukaryotic cells assemble an actomyosin ring during cytokinesis to function as a force-generating machine to drive membrane invagination, and to counteract the intracellular pressure and the cell surface tension. It is unclear whether additional factors such as the extracellular matrix (cell wall in yeasts and fungi) affect the actomyosin ring contraction. While studying the fission yeast {beta}-glucan synthase mutant cps1-191, which is defective in division septum synthesis and actomyosin ring contraction, we found that significantly weakening of the extracellular glycan matrix caused the spheroplasts to divide at the non-permissive condition. This division was dependent on a functional actomyosin ring and vesicular trafficking, but independent of normal septum synthesis. cps1-191 cells with weakened extracellular glycan matrix divide non-medially with a much slower ring contraction rate compared to wild type cells under similar conditions, which we term as cytofission. Interestingly, the high turgor pressure appears to play minimal roles in inhibiting ring contraction in cps1-191 mutants as decreasing the turgor pressure alone does not enable cytofission. We propose that during cytokinesis, the extracellular glycan matrix restricts actomyosin ring contraction and membrane ingression, and remodeling of the extracellular components through division septum synthesis relieves the inhibition and facilitates actomyosin ring contraction.

cell biology↗

bioRxiv2018

Stabilising and destabilising kinesin complexes queue at plus tips to ensure microtubule catastrophe at cell ends

In fission yeast, the length of interphase microtubule (iMT) arrays are adapted to cell length so as to maintain cell polarity and to help centre the nucleus and cell division ring. Here we show that length regulation of iMTs is dictated by spatially-regulated competition between MT-stabilising Tea2/Tip1/Mal3 (Kinesin-7) and MT-destabilising Klp5/Klp6/Mcp1 (Kinesin-8) complexes at iMT plus tips. During MT growth, the Tea2/Tip1/Mal3 complex remains bound to the plus tips of iMT bundles and restricts access to the plus tips by Klp5/Klp6/Mcp1, which accumulates behind it. At cell ends, Klp5/Klp6/Mcp1 invades the space occupied by the Tea2/Tip1/Tea1 kinesin complex triggering its displacement from iMT plus tips and MT catastrophe. These data show that in vivo, whilst the \"antenna model\" for iMT length- and age-dependent catastrophase accumulation has validity, length control is an emergent property reflecting spatially-regulated competition between multiple complexes at the MT plus tip.

cell biology↗