Decoding astrocyte natural rhythms: Impact of actin and channel protein dynamics across scales
Abstract
The goal of the present proposal is to investigate the contributions of the cytoskeleton to the function of non neuronal brain cells, called astrocytes. Three institutions – the University of Maryland, CNR, and UNIBA (Italy) – will work together to achieve a common goal while at the same time establishing an international collaboration. In the proposed work, we will explore the biophysical and molecular mechanisms that govern cytoskeletal properties in astrocytes. The molecular and functional correlation between the cytoskeleton and membrane bound channels will be investigated. In particular, we will focus on the non classical biophysics of these interactions. We will use in vitro cell culture models of polarized astrocytes, where cells resemble the in vivo phenotype, allowing for more representative studies at several relevant spatial scales. Primary cultures will be prepared from wild type (WT) rodents as well as from genetically modified mice. The effect of non classical dynamics on astrocyte homeostatic function will be studied with the long term goal of exploring astrocyte neuron signaling (gliotransmission). We will investigate dynamics across multiple lengthscales (from as small as nm to as large as mm) and timescales (from millisecond events to as long as minutes) by means of state of the art microscopy. These techniques will be combined with super resolution imaging techniques as well as with electrophysiology and membrane measurements to provide biophysical insights. We will utilize a combination of biophysical modeling and machine learning approaches to extract actionable insights from these multi faceted and multidimensional measurements. The ultimate goals of this investigation are to develop a novel approach to modulate astrocyte function based on intracellular signals and, in the future, to use astrocyte modulation to enhance astrocyte’s role in neuronal operations, particularly cognition and regeneration.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 14, 2022
- Source ID
- FA95501910370
Entities
People
- Wolfgang Losert
Organizations
- Air Force Office of Scientific Research
- United States Air Force
- University of Maryland