Biology subjects

Fai, T. G.

Publications and source records attributed to Fai, T. G..

4 recordsLinked to original sources

bioRxiv2025

Curvature-based machine learning method for automated segmentation of dendritic spines

AO_SCPLOWBSTRACTC_SCPLOWRecent advances in connectomics have been led by high-resolution reconstruction of large volumes of neural tissues using electron microscopy (EM), providing unprecedented insights into brain structure and function. Dendritic spines--dynamic protrusions on neuronal dendrites--play crucial roles in synaptic plasticity, influencing learning, memory, and various neurological disorders. However, current spine analysis methods often rely on manual annotation of subcellular features, limiting their ability to handle the complexity of spines in dense dendritic networks. This paper introduces a novel automated computational framework that integrates discrete differential geometry, machine learning, and 3D image processing to analyze dendritic spines in these intricate environments. By generating distributions of spine morphology from high resolution images including many thousands of spines, our approach captures subtle variations in spine shapes, offering a nuanced understanding of their roles in synaptic function. This framework is tested on multiple EM datasets, with the aim of enhancing our understanding of synaptic plasticity and its alterations in disease states. The proposed method is poised to accelerate neuroscience research by providing a scalable, objective, and comprehensive solution for spine analysis, uncovering insights into the role of spine geometry for neural function.

neuroscience↗

bioRxiv2023

Passive endocytosis in protocells enables nutrient transport bypassing permeability limits

Semipermeable membranes are a key feature of all living organisms. While specialized membrane transporters in cells can import otherwise impermeable nutrients, the earliest cells would have lacked a mechanism to import nutrients rapidly under nutrient-rich circumstances. Using both experiments and simulations, we find that a process akin to passive endocytosis can be recreated in model primitive cells. Molecules that are too impermeable to be absorbed can be taken up in a matter of seconds in an endocytic vesicle. The internalized cargo can then be slowly released over hours, into the main lumen or putative cytoplasm. This work demonstrates a way by which primitive life could have broken the symmetry of passive permeation prior to the evolution of protein transporters.

biophysics↗

bioRxiv2022

Quantitative mapping of synaptic periactive zone architecture and organization

1.Following exocytosis at active zones, synaptic vesicle membranes and membrane-bound proteins must be recycled. The endocytic machinery that drives this recycling accumulates in the periactive zone (PAZ), a region of the synapse adjacent to active zones, but the organization of this machinery within the PAZ, and how PAZ composition relates to active zone release properties remains unknown. The PAZ is also enriched for cell adhesion proteins, but their function at these sites is poorly understood. Here, using Airyscan and STED imaging of Drosophila synapses, we develop a quantitative framework describing the organization and ultrastructure of the PAZ. Different endocytic proteins localize to distinct regions of the PAZ, suggesting that sub-domains are specialized for distinct biochemical activities, stages of membrane remodeling, or synaptic functions. We find that the accumulation and distribution of endocytic but not adhesion PAZ proteins correlate with the abundance of the scaffolding protein Bruchpilot at active zones - a structural correlate of release probability. These data suggest that endocytic and exocytic activities are spatially correlated. Taken together, our results provide a new approach to quantify synaptic architecture and identify novel relationships between the exocytic and endocytic apparatus at the synapse.

neuroscience↗

bioRxiv2018

Length regulation of multiple flagella that self-assemble from a shared pool of components

Control of organelle size is a problem that has intrigued cell biologists for at least a century. The single-celled green algae Chlamydomonas reinhardtii with its two 2agella has proved to be a very useful model organism for studies of size control. Numerous experiments have identi1ed motor-driven transport of tubulin to the growing ends of microtubules at the tip of the 2agella as the key component of the machinery responsible for controlling their length. Here we consider a model of 2agellar length control whose key assumption is that proteins responsible for the intra2agellar transport (IFT) of tubulin are present in limiting amounts. We show that this limiting-pool assumption and simple reasoning based on the law of mass action leads to an inverse relationship between the rate at which a 2agellum grows and its length, which has been observed experimentally, and has been shown theoretically to provide a mechanism for length control. Experiments in which one of the two 2agella are severed have revealed the coupled nature of the growth dynamics of the two 2agella, and we extend our length-control model to two 2agella by considering different mechanisms of their coupling. We describe which coupling mechanisms are capable of reproducing the observed dynamics in severing experiments, and why some that have been proposed previously are not. Within our theoretical framework we conclude that if tubulin and IFT proteins are freely exchanged between 2agella simultaneous length control is not possible if the disassembly rate is constant. However, if disassembly depends on the concentration of IFT proteins at the tip of the 2agellum, simultaneous length control can be achieved. Finally, we make quantitative predictions for experiments that could test this model.

systems biology↗