Biology subjects

Vaggi, F.

Publications and source records attributed to Vaggi, F..

3 recordsLinked to original sources

bioRxiv2018

The chaperone-client network subordinates cell-cycle entry to growth and stress

The precise coordination of growth and proliferation has a universal prevalence in cell homeostasis. As a prominent property, cell size is modulated by the coordination between these processes in bacterial, yeast and mammalian cells, but the underlying molecular mechanisms are largely unknown. Here we show that multifunctional chaperone systems play a concerted and limiting role in cell-cycle entry, specifically driving nuclear accumulation of the G1 Cdk-cyclin complex. Based on these findings, we establish and test a molecular competition model that recapitulates cell-cycle-entry dependence on growth rate. As key predictions at a single-cell level, we show that availability of the Ydj1 chaperone and nuclear accumulation of the G1 cyclin Cln3 are inversely dependent on growth rate and readily respond to changes in protein synthesis and stress conditions that alter protein folding requirements. Thus, chaperone workload would subordinate Start to the biosynthetic machinery and dynamically adjust proliferation to the growth potential of the cell.

molecular biology↗

bioRxiv2018

MuSCA: a multi-scale model to explore carbon allocation in plants

Background and aimsCarbon allocation in plants is usually represented at a specific spatial scale, peculiar to each model. This makes the results obtained by different models, and the impact of their scale of representation, difficult to compare. In this work we developed a Multi Scale Carbon Allocation model (MuSCA) that can be applied at different, user-defined, topological scales of a plant, and used to assess the impact of each spatial scale on simulated results and computation time.\n\nMethodsModel multi-scale consistency and behavior were tested by applications on three realistic apple tree structures. Carbon allocation was computed at five spatial scales, spanning from the metamer (the finest scale, used as a reference) up to 1st order branches, and for different values of a sap friction coefficient. Fruit dry mass increments were compared across spatial scales and with field data.\n\nKey ResultsThe model showed physiological coherence in representing competition for carbon assimilates. Results from intermediate values of the friction parameter best fitted the field data. For these, fruit growth simulated at the metamer scale (considered as a reference) differed from about 1% at growth unit scale up to 35% at first order branch scale. Generally, the coarser the spatial scale the more fruit growth diverged from the reference and the lower the obtained within-tree fruit growth variability. Coherence in the carbon allocated across scales was also differently impacted, depending on the tree structure considered. Decreasing the topological resolution reduced computation time up to four orders of magnitude.\n\nConclusionsMuSCA revealed that the topological scale has a major influence on the simulation of carbon allocation, suggesting that this factor should be carefully evaluated when using different carbon allocation models or comparing their results. Trades-off between computation time and prediction accuracy can be evaluated by changing topological scales.

plant biology↗

bioRxiv2017

Reconstructing regulatory pathways by systematically mapping protein localization interdependency networks

A key goal of functional genomics is to elucidate how genes and proteins act together in space and time, wired as pathways, to control specific aspects of cell biological function. Here, we develop a method to quantitatively determine proteins localization interdependencies at high throughput. We show that this method can be used to systematically obtain weighted, signed and directional pathway relationships, and hence to reconstruct a detailed pathway wiring. As proof-of-principle, we focus on 42 factors that control cell polarity in fission yeast (Schizosaccharomyces pombe) and use high-throughput confocal microscopy and quantitative image analysis to reconstruct their Localization Interdependency Network (LIN). Through this approach we identify 554 pairwise interactions across the factors, including 98% putative new directed links. Validation of an unexpected interaction between two polarity factor subgroups - the polarity landmark proteins and the cell integrity pathway components - by orthogonal phenotyping demonstrates the power of the LIN approach in detecting subtle, systems-level causal connections.

cell biology↗