Research
"The brain is a world consisting of a number of unexplored continents and great stretches of unknown territory." - Santiago Ramon y Cajal,
The brain, a marvelously complex organ, presents a myriad of challenges when it comes to investigating and treating brain diseases. To comprehend how a healthy brain operates and what goes wrong in brain disorders, it is crucial to provide a complete depiction of the intricate network of molecules and biochemical processes that span diverse brain regions and varying time periods. Molecular imaging, a well-established technique in biological research, stands as a valuable tool for uncovering the mysteries of the brain. To advance brain research, gain a deeper understanding of neurological disorders, and develop effective therapies, the Su Lab is focused on creating innovative ways to use molecular imaging in brain disease research. These efforts include:
Pioneering generalizable bioluminescent biosensor designs for brain disease research
Precise molecular sensing is crucial for studying brain diseases and advancing treatments. There is a need for genetically encoded optical biosensors to elucidate biological signals in living animals. While conventional fluorescent protein biosensors require time-consuming optimization and are not ideal for deep imaging inside the brain, bioluminescence offers an alternative for in-brain applications. It is good in sensitivity and doesn't have background noise in animal brains. Despite its potential, the development of bioluminescent biosensors remains limited. Our lab aims to advance the field by inventing innovative, universally applicable designs for bioluminescent biosensors.
Advancing brain disease drug development through optical protein biosensors
Biosensors are tools that let us see in real-time how drugs are acting in animal brains, significantly enhancing drug development. Brain disease drug development faces unique challenges such as the blood-brain barrier and the absence of suitable preclinical models for assessing target engagement. Current methods involving animal sacrifice and biochemical analysis are resource-intensive and ethically tricky. Alternative techniques like radioactive labeling and imaging are costly and lack efficiency. Furthermore, the complicated relationships between drug concentration, occupancy, and efficacy necessitate direct monitoring of drug effects in the brain. To reduce costs and risks in brain disease drug development, our lab is dedicated to a novel approach—utilizing optical biosensors in animal brains to evaluate the efficiency of potential drugs.
Illuminating neurological disorders by probing abnormal protein behaviors with optical biosensors
Abnormal protein behaviors, like irregular post-translational modifications and aggregation, are important hallmarks in neurological disorders. Studying these mechanisms and developing effective therapies face limitations in monitoring these aberrant protein behaviors in cell-based and in vivo models. Particularly, traditional in vivo assessments depend on phenotypic studies - observing behavioral changes in aged animals over time. Due to the slow effects and the absence of quantifiable biomarkers, these studies are usually hard to conduct, costly and time-consuming. To speed up neurodegenerative disease research, our lab is committed to developing sensitive optical reporters for non-invasive, longitudinal monitoring of abnormal protein behaviors in both cellular and in vivo contexts.
Advancing multiplex imaging for brain research by innovating protein reporter systems
Existing luciferase-luciferin systems optimized for in-brain applications are limited in number and still have room for improvement. Brain disease research, with its complex mechanism, often requires simultaneous tracking of multiple events via orthogonal reporter systems, as assessing a single target or pathway falls short. Unfortunately, the pursuit of multiplex bioluminescent biosensing faces limitations due to the lack of luciferase-luciferin choices for brain applications. Our lab aims to expand this repertoire and establish a diverse toolbox of bioluminescent sensors by utilizing existing systems and/or engineering under-explored wild-type luciferases.
