Skip to main content
European Commission logo print header

Biophysical Properties of the Neuronal Cytosol and their Dynamics upon Nutrient Starvation, Aging, and in Neurodegenerative Diseases.

Project description

Insight into the role of the cytosol in neurodegeneration

The cytosol is the semi-liquid substance that fills the cell's inner part where many biochemical reactions, including protein synthesis, occur. Accumulating evidence indicates that the cytosol regulates diffusive transport, but little is known about cytosol dynamics and how it varies between cells. The EU-funded NeuroFreezing project will focus on the neuronal cytosol and how stress, such as nutrient deprivation and ageing, can affect its function and properties. Researchers will employ state-of-the-art techniques to assess cytosol's role in protein aggregation observed in Huntington's disease neurons, paving the way towards novel therapeutic strategies.


The material properties of the cytosol control the biochemistry of the cell and influence all molecular interactions by regulating rates of intracellular diffusive transport. Despite this critical role, these properties remain poorly understood, and it is unclear to what extent the cytosol is homogeneous, whether there are differences between cell types, and if these properties are stable or dynamic. It has recently been discovered that yeast cells regulate their cytosolic properties in response to stress, namely glucose-starvation and aging. These stresses result in a decrease in cell volume and an increase in cytosolic crowding, inducing widespread phase separations and aggregation of polyglutamine (polyQ)-proteins. This type of polyQ-protein aggregation is the molecular hallmark of neurodegenerative diseases like Huntington's Disease (HD), and is very poorly understood. In this project, I will produce the first description of the biophysical properties of the neuronal cytosol, and I will directly test whether aged or nutrient-deprived neurons, or neurons from an HD mouse model exhibit changes in these properties. I propose that viscosity and density of mammalian cells, and in particular neuronal cells, are dynamic properties that can be actively regulated in response to environmental changes. In particular, I will test two hypotheses: - H1: Nutrient starvation and aging induce changes to the material properties of the neuronal cytosol. - H2: A neuronal stress-response upon starvation or aging is sufficient to trigger aggregation of polyQ-proteins. Combining state-of-the-art techniques and expertise in the fields of neurobiology, metabolism, and biophysics, my investigation of these novel and potentially paradigm shifting hypotheses could fundamentally alter our understanding of the material properties of the neuronal cytosol, and ultimately reveal new therapeutic strategies for the most common inherited neurodegenerative disorders.


Net EU contribution
€ 203 149,44
Raemistrasse 101
8092 Zuerich

See on map

Schweiz/Suisse/Svizzera Zürich Zürich
Activity type
Higher or Secondary Education Establishments
Other funding
€ 0,00