Laboratory of Chemical Neurobiology
Research Field
I have a multi‐disciplinary background which covers organic chemistry, biochemistry, ion channel biophysics, optogenetic technology, and neurobiology. Since postdoctoral training, I have been developing optogenetic and photopharmacological tools for precise manipulation of neurotransmission in the brain. After starting my independent position at Academia Sinica, I continued to develop new and better molecular tools for neurotransmission decoding. My ultimate goal is to apply our tools to investigate complex physiological and pathological phenomena such as synaptic plasticity, neuron-cancer communications, and brain-body interactions.
The central nervous system (CNS) is operated by complex and dynamic cellular networks that generate functional outputs in response to sensory cues and/or physiological changes. Neurotransmission, the process that mediates the communication and interplay between neurons, is fundamental for CNS function and development. While its biomedical significance has been well recognized, the mechanistic understanding of neurotransmission in health and diseases remains largely obscure, as signaling molecules involved in neurotransmission are enormously diverse. Moreover, the distribution profile of neurotransmitters and their receptors is highly heterogeneous and varies dynamically. Studying neurotransmission with conventional approaches (e.g., pharmacology or gene knock-out/knock-in) has thus encountered critical obstacles.
My laboratory integrates chemical, biochemical, and genetic approaches to develop enabling technologies for precise manipulation of neurotransmission. We focus on molecular tools that allow light to control either the function of neurotransmitter receptors or the release of neurotransmitters from axonal terminals. These biological activities are therapeutic targets for many neurological, psychiatric, and developmental disorders. Knowing why and how the CNS utilizes these signaling mechanisms will bring an exciting new dimension to our understanding of brain function, dysfunction, and development.
- Develop novel methods to optically control native neurotransmitter receptors.
- Develop optogenetic actuators to manipulate the function of synapses or neuropathways.
- Apply new optogenetic tools to manipulate synaptic plasticity or body sensation.
(2005 ‒ 2007) Merck-MIT Predoctoral Fellowship, Massachusetts Institute of Technology (USA)
(2021) Career Development Award, Academia Sinica (Taiwan)
B.S. and M.S. in Chemistry, National Taiwan University (Taiwan)
Ph.D. in Biological Chemistry, Massachusetts Institute of Technology (USA)
Postdoctoral Scholar, University of California, Berkeley (USA)
Associate Specialist, University of California, Berkeley (USA)
Job Description
[option #1: Optogenetic Tool Development]
An intern interested in optogenetic tool development will participate in the engineering of next-generation optogenetic neuron silencers. This project requires a deep analysis of the structure-function relationship of an opsin and a series of cloning/mutagenesis to construct variants with improved performance or new functionalities. After new DNA clones are constructed, they will be expressed in mammalian cell lines or cultured neurons to test their expression patterns or functional properties.
[option #2: Optogenetic Tool Validation]
An intern interested in optogenetic tool validation will assist in the evaluation of new optogenetic tools (developed by our lab) in mice. Works may include (but not limited to) tissue harvesting, immunohistochemical analysis, advanced microscopy, or behavioral tests (depending on the student's own skill set).
Preferred Intern Educational Level
[option #1: Optogenetic Tool Development] Master's students or senior undergraduate students in chemistry, biochemistry, biophysics/structural biology, molecular/cell biology, or bioengineering.
[option #2: Optogenetic Tool Validation] Master's students or senior undergraduate students in neuroscience, physiology, pharmacology, biomedical sciences, bioengineering/biomedical engineering, or related life science disciplines.
Students aiming to pursue PhD training or an research-oriented career are welcomed.
Skill sets or Qualities
[option #1: Optogenetic Tool Development] Applicants should be highly familiar with standard cloning, biochemistry, and molecular biology techniques (i.e., can perform tasks independently without intense tutoring). Students with additional lab experience in structural biology, cell biology, microscopy, or electrophysiology are preferred. A strong interest in molecular design, protein engineering, and technology development is required.
[option #2: Optogenetic Tool Validation] Applicants should have a substantial training in mouse behavioral experiments or handling. Students with additional lab experience in immunohistochemistry, confocal microscopy, or electrophysiology are preferred. Essential concepts in neuroscience, anatomy, and optogenetic technologies are required.
General requirements: good understanding and strong interest in optogenetics, high motivation for self-education, proactive learning and communication, critical thinking, capability of participating in cross-disciplinary and collaborative projects