Challenge: In the human brain and retina, the chemical glutamate is a very important messenger that carries information from one neuron to another. The levels of glutamate transmitted between neurons must be tightly controlled: too high and neurons die, too low and information is not communicated properly. In either case this can contribute to neurological diseases including stroke, glaucoma, and Alzheimer’s. Glutamate levels are controlled by glial cells found next to neurons, and they do this by taking up glutamate through one of two types of transporter proteins on their surface called EAATs. The EAATs are very attractive targets for the development of new drug therapies. However, compounds that modify EAAT function have been difficult to identify due to a lack of available tools.
Solution: Cyto-iGluSnFR (pronounced “sight-oh-eye-glue-sniffer”) is a new breakthrough technology that the team intends to adapt for the discovery of EAAT-based drugs to treat a variety of brain and eye diseases. Cyto-iGluSnFR is an engineered protein that senses glutamate, allowing scientists to see and measure the rate by which glutamate enters cells. With this funding the team plans to adapt this Cyto-iGluSnFR glutamate biosensor in order to enable millions of chemicals to be screened in order to find drugs that make EAATs either more or less effective at moving glutamate into glial cells. These potential drugs can then be further tested using the very same biosensor in laboratory mice – where neurons and glial cells function as they do in humans – in order to make sure they are safe and effective for patients.
Impact: The Cyto-iGluSnFR platform is likely to have impact at each of the following main steps in the drug discovery process: Target identification, Discovery/Screening, Lead optimization, and Preclinical Testing. By adapting Cyto-iGluSnFR for multiple stages of drug development and testing, our team of experts will build a comprehensive platform to accelerate progress toward new therapies for brain and eye diseases.
Don van Meyel
Adriana Di Polo
Timothy H. Murphy