Biology subjects

Nollen, E.

Publications and source records attributed to Nollen, E..

2 recordsLinked to original sources

bioRxiv2021

Optogenetic manipulation of individual or whole population Caenorhabditis elegans worms with an under hundred-dollar tool: the OptoArm

AbstractOptogenetic tools have revolutionized the study of neuronal circuits in Caenorhabditis elegans. The expression of light-sensitive ion channels or pumps under specific promotors allows researchers to modify the behavior of excitable cells. Several optogenetic systems have been developed to spatially and temporally photoactivate light-sensitive actuators in C. elegans. Nevertheless, their high costs and low flexibility have limited wide access to optogenetics. Here, we developed an inexpensive, easy-to-build, and adjustable optogenetics device for use on different microscopes and worm trackers, called the OptoArm. The OptoArm allows for single- and multiple-worm illumination and is adaptable in terms of light intensity, lighting profiles and light-color. We demonstrate the OptoArms power in a population-based study on contributions of motor circuit cells to age-related motility decline. We find that functional decline of cholinergic neurons mirrors motor decline, while GABAergic neurons and muscle cells are relatively age-resilient, suggesting that rate-limiting cells exist and determine neuronal circuit aging.

genetics↗

bioRxiv2021

Deletion of Serf2 shifts amyloid conformation in an Aβ amyloid mouse model

In age-related neurodegenerative disease, like Alzheimers and Parkinsons disease, disease-specific proteins become aggregation-prone and form amyloid-like deposits. Depletion of SERF proteins ameliorates this toxic process in worm- and human cell models for disease. Whether SERF modifies amyloid pathology in mammalian brain, however, has remained unknown. Here, we generated SERF2 brain-specific knockout mice which, unlike full body knockout mice, were viable, and showed no major behavioral and cognitive abnormalities. We combined these knockout mice with the APPPS1 mouse model for human amyloid beta aggregation. Using structure-specific amyloid dyes, previously used to distinguish amyloid polymorphisms in human brain, we show that knockout of SERF2 alters the structure of amyloid fibrils and deposits. Moreover, scanning transmission electron microscopy revealed thicker, shorter and more densely packed amyloid in absence of SERF2. Altogether, our data reveal pleiotropic functions of SERF in development and aging and support a function as a modifier of amyloid aggregation in mammalian brain. Our results indicate that single cellular factors like SERF can determine the structural outcome of amyloid aggregation, offering possibilities for polymorphism-based disease interventions.

molecular biology↗