Project description
Unlocking the mechanism behind serious brain diseases
Glutamate is a key neurotransmitter in the brain, closely tied to memory formation. It is also linked to serious neurological diseases such as Alzheimer’s and Parkinson’s. Therefore, it is considered vitally important to monitor glutamate levels in great detail. The EU-funded F4TGLUT project aims to develop a groundbreaking and highly sensitive method for monitoring glutamate levels at a cellular level in the human brain. The goal is to help better explain the underlying mechanisms behind serious brain diseases and common mental conditions affecting people globally. The project should shed more light on glutamate neurotransmission and how drugs and diet can affect it.
Objective
Glutamate is the primary activating neurotransmitter in the brain. It modulates synaptic plasticity of neurons, which underlies memory formation. However, it also plays a fundamental role in pathological processes, such as those related to Alzheimer’s disease. This essential role and future development of therapeutic agents urge the development of a highly-sensitive analytical method for determining glutamate levels at a cellular level. In this project I will create a miniaturized, in vitro system that will allow this. To develop it, my expertise in microfluidics and pharmacy will be supplemented by the host’s extensive experience with cell analysis and nanoelectrodes.
When glutamate-type neurons in the brain are innervated, glutamate release into the synapse between adjacent neurons occurs. This triggers chemical signal transmission. Nanoelectrodes are uniquely equipped to monitor this neurotransmitter release with unprecedented spatiotemporal resolution. The combination with microfluidics will allow control of fluids and experiments at the nanoliter scale. Furthermore, through precisely fabricated microstructures, guidance of cell growth and precise placement of the nanoelectrodes in the device will be achieved.
Glutamate modulates synaptic plasticity, a phenomenon understood to underlie memory formation. Furthermore, dietary compounds and drugs can influence glutamate neurotransmission. The proposed system enables selective exposure of individual neurons cultured in the microfluidic device to such compounds. Using the integrated nanoelectrodes, direct monitoring of their effects on chemical signaling between cells will be possible. The results will significantly contribute to our understanding of glutamate neurotransmission, and how drugs and diet can influence it. Additionally, the system combines cell culture, selective exposure and analyses at the cellular level using sensors and imaging, making it an ideal platform for future drug development research.
Fields of science
Not validated
Not validated
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- natural sciencesphysical sciencesclassical mechanicsfluid mechanicsmicrofluidics
- medical and health scienceshealth sciencesnutrition
- engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensors
Keywords
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
405 30 Goeteborg
Sweden