Neurodegenerative diseases are a collective name for the disorders characterized by the gradual damage of the nervous system, leading to conditions such as dementia, depression, motor dysfunction, and muscle stiffness. Currently, over 50 million people are affected by these diseases worldwide, with more than 120,000 patients in Taiwan. Due to the association between these diseases and age, the number of affected individuals is growing at an alarming rate in the trend of population aging.
Neurodegenerative diseases are hard to cure. They can only be managed through prevention or symptom control. One challenge in pharmacological therapies is how to impact the nervous system with minimizing side effects. Therefore, we aim to develop an improved plant-based manufacturing to produce medicine with higher bioactivity. We choose Nicotiana benthamiana as the expression platform. By introducing plasmids to express enzymes like AD6 (to catalyze the conversion of tyrosine to levodopa), ADH (to catalyze the conversion of arogenate to tyrosine), and P19 (as RNA silencing suppressor), we plan to produce levodopa, a common medication for Parkinson's disease. Then we create zebrafish models of Parkinson’s disease to test the effectiveness of the product. Additionally, we disseminate information about neurodegenerative diseases to increase public awareness to help with prevention and assist those suffering from these diseases.
To reduce variables and accelerate the experimental timeline, we have selected tobacco as our expression platform. Tobacco does not contain the enzymes required to convert tyrosine to levodopa, preventing product loss through natural growth. Furthermore, using tobacco for production and experimentation is only a few weeks, making it suitable for multiple engineering cycles and gradual improvements in experimental design. Finally, yield is analyzed through HPLC.
Zebrafish are commonly used as a model animal for drug efficacy research, especially for human-related studies. Zebrafish can present the desired conditions with low doses of drugs, have a genome highly similar to humans, and possess a well-developed nervous system. Additionally, zebrafish are rapidly cultured, making them ideal for multiple engineering cycles. Then we will administer fixed doses of the drug, conduct behavioral analysis through an analysis system and chemical immunostaining for visual results.
AI has the potential to accelerate experimental cycles, but its application depends on the establishment of comprehensive databases. Even though the tobacco database is still insufficient, we still attempted to build a small-scale AI model to explore the possibilities of AI in synthetic biology.
We aim to design a swimming tunnel for evaluating swimming performance of zebrafish larvae to provide more accurate experimental data analysis. This tunnel will use a propeller operating at a fixed frequency to maintain water flow, use the zebrafish's natural tendency to swim against the current to measure their behavior under stimulation.