Team:XJTLU-CHINA/Description

Background

Astrocytic dysfunction has been extensively implicated in the pathogenesis of numerous diseases, which include Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) and so on. Although the primary causes of these diseases have not yet been identified, the decreased glutamate transporters expression on the membrane is one of the consequences. However, due to the decline of the transporter levels at the early stage of these diseases, astrocytic dysfunction would accelerate the accumulation of glutamate, which is a potent neurotoxin and provides a highly unfit environment for the cells in the brain to survive. Therefore, action should be taken more urgently as soon as a sign of astrocytic dysfunction is diagnosed.

Why did we choose this project?

At the beginning of this iGEM year, we first organized a campus-competition called 'XJTLU iDeamer' to stimulate the iGEM competition. Throughout the competition, more than 30 students participated in nominating the researchfield they were interested in, including depression, a cosmetic composition, aerial vehicle, and so on. By organizing this activity, we got acquainted with many students interested in the topics of disease treatment. Inspired by their ambition, we made up the idea on a therapeutic project. Since we have two members from the 2018 team, they suggested we could keep on working on the clinical application on using exosomes. After the first brainstorm meeting, we decided on a topic related to treating neurodegenerative diseases.

How did we choose this project?

After discussing with Dr. Minyan Wang, an expert in neuroscience in our department, we figured out that the protein Excitatory Amino Acid Transporter (EAAT2) may be a target in the nerve cell in treating early neurodegenerative diseases. Since then, we began working both literally and physically on the project. Also, once we had a general idea on the topic of this year's project, we communicated with our PI, Dr. Dechang Xu. He suggested us to build up models to study the regulation of the behaviour of the exosomes, which is especially related to the principle of synthetic biology. Together with our work, we finally came up with the Three-Plasmid Regulation model.

What are we going to do?

Our primary goal is to save astrocytes from the high glutamate level at the early stage of neurodegenerative disease and to strengthen the defence against the neurotoxicity. In details, we design this therapy to enhance the glutamate absorbing function by overexpression of the protein EAAT2 on the astrocyte’s membrane. We use the mRNA-based vector for expression and protect the mRNA by exosome during the delivery process. We further study the production, characterization, transportation, preservation and other related topics on the exosome therapy, and subsequently, carry out several social activities on topics related to exosome treatment to enhance our design.

Significance of our project in the synthetic biology

The implications of our project in synthetic biology are very valuable. Our project has promising applications in the medical field and the production of efficient and improved mRNA drugs for targeted therapy of neurodegenerative diseases. We apply a synthetic biology engineering technology platform and follow theirprinciples, on the other hand, we explore the structural principles of molecular machines, realize the optimization design, improve the network synthesis ability and control ability in order to produce meaningful results as much as possible. On the basis of the understanding from analysis to synthesis, the idea of our biological research rises to a higher level on the synthesis and construction of a complex living system.