Project description
Neuronal glycocalyx and brain development
The neuronal glycocalyx is a carbohydrate-rich layer enveloping the surface of neurons within the brain. It is believed to play a crucial role in synapse formation, neuronal signalling and brain network development. A key constituent of this layer is sialic acid, an integral part of the glycoproteins and glycolipids encountered on the surface of neurons. Although disruption of neuronal sialylation is associated with several brain disorders, the mechanisms remain unclear. The ERC-funded GLYCOCIRC project aims to investigate the mechanisms by which sialic acid influences development of the human brain. Researchers will study how sialic acid modulates brain circuits during development and shapes interactions between neurons and microglia during critical periods of brain maturation.
Objective
Neuronal glycocalyx has been recently recognized as an active agent that contributes to neuronal synapse formation, neuron excitability as well as neuron-autonomous and microglia-dependent brain network remodelling. In particular, the glycan-terminating sialic acids, which often dominate the ends of the chains of glycoproteins and glycolipids on neuronal surface, are required for appropriate brain development and function. Interestingly, almost a fifth of sialic acid biology genes have human-specific changes and aberrant neuronal sialylation and desialylation are implicated in different neurodevelopmental and neuropsychiatric conditions. Thus, I hypothesize than neuronal glycocalyx and specifically its component sialic acid in particular have a critical role in the formation of unique human brain. Despite its recognized importance, there is still a lack of mechanistic understanding filling the knowledge gap how synapses are shaped by the dynamics of the glycocalyx. Therefore, here I propose to merge my expertise in biochemistry and neuroscience to tackle this challenging area of research to further our knowledge of brain sialome through evolutionary approach. We will use in vitro, ex vivo and in vivo models from humans, non-human primates and mouse that can be modified at genetic level for selective labelling and modification of neuronal cells and will combine it with advanced microscopy techniques as well as synaptic-level molecular analysis. We will demonstrate how the glycocalyx and sialic acid act as a defining factor for neural circuitry formation and refinement in developing brain, in particular through the interaction of neurons and their synapses with brain immune cells – microglia. Our results will advance our understanding of fundamental contribution of the glycocalyx to brain physiology and pathology with the translatability to human conditions, thus paving potential ways to develop treatment for brain network disorders.
Fields of science (EuroSciVoc)
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- natural sciences biological sciences neurobiology
- natural sciences biological sciences biochemistry
- medical and health sciences basic medicine pathology
- medical and health sciences basic medicine physiology
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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(opens in new window) ERC-2024-COG
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01513 Vilnius
Lithuania
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