Biology subjects

Fröhlich, F.

Publications and source records attributed to Fröhlich, F..

3 recordsLinked to original sources

bioRxiv2018

A Systematic Approach to Identify Recycling Endocytic Cargo Depending on the GARP Complex

Proteins and lipids of the plasma membrane underlie constant remodeling via a combination of the secretory- and the endocytic pathway. In the yeast endocytic pathway, cargo is sorted for recycling to the plasma membrane or degradation in vacuoles. In a previous paper we have shown a role for the GARP complex in sphingolipid sorting and homeostasis (Frohlich et al. 2015). However, the majority of cargo sorted in a GARP dependent process remain largely unknown. Here we use auxin induced degradation of GARP combined with mass spectrometry based vacuolar proteomics and lipidomics to show that recycling of two specific groups of proteins, the amino-phospholipid flippases and cell wall synthesis proteins depends on a functional GARP complex. Our results suggest that mis-sorting of flippases and remodeling of the lipid composition are the first occurring defects in GARP mutants. Our assay can be adapted to systematically map cargo of the entire endocytic pathway.

cell biology↗

bioRxiv2018

MIN1PIPE: A Miniscope 1-photon-based Calcium Imaging Signal Extraction Pipeline

In vivo calcium imaging using 1-photon based miniscope and microendoscopic lens enables studies of neural activities in freely behaving animals. However, the high and fluctuating background, the inevitable movements and distortions of imaging field, and the extensive spatial overlaps of fluorescent signals emitted from imaged neurons inherent in this 1-photon imaging method present major challenges for extracting neuronal signals reliably and automatically from the raw imaging data. Here we develop a unifying algorithm called MINiscope 1-photon imaging PIPEline (MIN1PIPE) that contains several standalone modules and can handle a wide range of imaging conditions and qualities with minimal parameter tuning, and automatically and accurately isolate spatially localized neural signals. We quantitatively compare MIN1PIPE with other existing partial methods using both synthetic and real datasets obtained from different animal models, and show that MIN1PIPE has a superior performance both in terms of efficiency and precision in analyzing noisy miniscope calcium imaging data.

neuroscience↗

bioRxiv2017

Mechanistic hierarchical population model identifies latent causes of cell-to-cell variability

All biological systems exhibit cell-to-cell variability, and this variability often has functional implications. To gain a thorough understanding of biological processes, the latent causes and underlying mechanisms of this variability must be elucidated. Cell populations comprising multiple distinct subpopulations are commonplace in biology, yet no current methods allow the sources of variability between and within individual subpopulations to be identified. This limits the analysis of single-cell data, for example provided by flow cytometry and microscopy. In this study, we present a data-driven modeling framework for the analysis of populations comprising heterogeneous subpopulations. Our approach combines mixture modeling with frameworks for distribution approximation, facilitating the integration of multiple single-cell datasets and the detection of causal differences between and within subpopulations. The computational efficiency of our framework allows hundreds of competing hypotheses to be compared, giving unprecedented depth of a study. We demonstrated the ability of our method to capture multiple levels of heterogeneity in the analyzes of simulated data and data from highly heterogeneous sensory neurons involved in pain initiation. Our approach identified the sources of cell-to-cell variability and revealed mechanisms that underlie the modulation of nerve growth factor-induced Erk1/2 signaling by extracellular scaffolds.

systems biology↗