Illuminating the puzzle of zinc signaling in neurons: defining the dynamics of synaptic zinc signaling

Active Project Grant Awarded Last action

Award ID
F31NS151476
Recipient
Awarding agency
Obligated
$43,681

Award facts

Assistance listing
93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
Completion date 0% complete
Place of performance
Boulder, CO 80303, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Zinc signaling is key for maintaining proper cellular function and organism health, by regulating cellular processes through transient binding with target proteins. Zinc binds many conserved proteins but also cell type specific proteins, enabling zinc to regulate specialized cellular processes, such as neuronal transmission. Despite the known interaction between zinc and key synaptic proteins little is known about the dynamics of the zinc signal that impacts these zinc-protein interactions. Free zinc is maintained in two pools at the synaptic level: cytosolic zinc and synaptic vesicle zinc. Each pool displays a neuronal activity dependent signal; cytosolic zinc levels transiently rise and synaptic vesicle zinc is released into the synapse, following neuronal activation. Neuronal zinc signaling is unique because IT possesses the ability to act as both an intra and extra cellular signal supporting the neuron's main function of information transmission. Despite the involvement of zinc signaling in supporting synaptic function, no studies have defined zinc signal dynamics at a single synapse level. Through the support of this fellowship, i will uncover the dynamics of these zinc pools and lay the foundation for a cellular map of neuronal zinc signaling. Identifying when and where zinc levels change at the synaptic and sub- neuronal levels will inform future research in neuronal regulation and models of neurodegenerative disorders, where zinc dysregulation often plays a role. I will develop a new zinc biosensor to quantify and track zinc levels in acidic organelles including synaptic vesicles. This will allow me to answer the question: how much zinc is within synaptic vesicles and lysosomes and how stable is that concentration? Current estimates of zinc concentrations in acidic organelles are imprecise, limiting our understanding of how these pools contribute to zinc signals. By combining an in-vitro synapse, constructed with hipsc derived neurons and a microfluidic device, with cytosolic zinc biosensors and advanced fluorescent microscopy, i will be able to define the dynamics of cytosolic zinc signaling at a synaptic and sub-neuronal level for the first time. I will answer the question: do zinc levels rise in the cytosol within both the pre and post synaptic neuron and do the levels rise locally or reach the soma? Defining this is important because IT will determine which pathways and proteins zinc is capable of differentially impacting in response to neuronal activity. This research plan will provide me with training in experimental design, image analysis, written communication, and further my neurobiology understanding. This interdisciplinary set of skills will help me to transition effectively to the next stage of my research career.

Quick answers

Who received award F31NS151476?

F31NS151476 was awarded to The Regents Of The University Of Colorado by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on February 26, 2027.

How much is award F31NS151476 worth?

$43,681 has been obligated on F31NS151476.

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