Dr. Lin, Wan-Chen ’s Lab林宛蓁 博士 實驗室

RESEARCH

RESEARCH BACKGROUND

The central nervous system (CNS) is operated by complex and dynamic cellular networks that generate functional outputs in response to sensory cues and physiological changes. Neurotransmission, which mediates the communication and interplay between neurons, is fundamental for CNS function and development. In recent years, nationwide projects have been launched across the world to map brain function and circuitry. One of the outstanding but yet unachieved goals is to comprehensively decode neurotransmission in the brain. This mission is enormously challenging, as signaling molecules involved in neurotransmission are highly diverse. For example, a neurotransmitter may act through multiple types of receptors which have various assemblies and cellular/subcellular distributions. Moreover, receptor actions change dynamically and span a broad range of timescales. Studying neurotransmission with conventional approaches (e.g., pharmacology or gene knock-out) has thus encountered critical obstacles. Breakthroughs in neurotransmission decoding await new methods that enable control over signaling mediators with high spatial, temporal, and biochemical precision.

We integrate chemical, biochemical, and genetic approaches to develop these methods, with a special focus on next-generation optogenetics. Optogenetics is a revolutionary technique for precise manipulation/probing of complex biological events such as cellular signaling and neural circuitry. Through the action of a light-sensitive protein, the physiology of a cell or an organism can be optically controlled in defined space and time. Photocontrol can be further confined to a cell type of interest via genetic manipulations, facilitating the dissection of neural circuitry. We focus on optogenetic manipulation of neurotransmitter receptors, the therapeutic targets for many neurological, psychiatric and developmental disorders. To gain mechanistic insights into their physiology and pathophysiology, we aim to develop new methods that provide precise control over specific receptor members, as well as tools that enable a comprehensive profiling of these proteins. Knowing why and how the CNS utilizes such a diverse set of signaling mediators will bring an exciting new dimension to our understanding of brain function, dysfunction, and development.

 

We Are Recruiting New members!

We welcome chemists, life scientists, and engineers who are enthusiastic about working at the interface of chemistry and neuroscience. Currently we have 1 Research Assistant Position and 1 Ph.D. Studentship (enrolling TIGP-MM, INS, or CBMB student in Fall, 2022) available. Prospective candidates wishing to develop light-sensitive GPCR modulators or employ optogenetic/chemogenetic tools in synaptic biology are strongly encouraged to apply. We also welcome highly motivated undergraduate students to pursue internship in our lab. Please email Dr. Lin directly if you are interested in any of these opportunities.  誠徵博士生、研究助理、以及大學部專題生,有興趣者請email林老師洽詢! 有高度熱忱想從事本領域之博士後研究者,請準備學術履歷(含publication list)以及研究目標之具體論述,再email林老師洽談可能性。

 

CURRENT PROJECTS

We currently tackle this challenge by two different approaches. First, we engineer light-sensitive neurotransmitter receptors for precise manipulation of specific signaling components in the CNS. These tools will facilitate optogenetic decoding of neurotransmission with high biochemical resolution. We have previously developed a series of light-sensitive GABAA receptors for precise control of neuronal inhibition, both in vitro and in vivo (NEURON, 2015) (JACS, 2018). On this basis, we are exploring new strategies to enhance the performance of the tools and to simplify the engineering procedures. We will also confer light sensitivity onto other neurotransmitter receptors, with a special interest in G-protein coupled receptors (GPCRs). Our ambitious goal is to generalize the approaches, expanding the optogenetic toolkit for a truly comprehensive decoding of neuronal signaling.

Second, we pursue novel methods to optically control native neurotransmitter receptors in defined neuronal types and/or subcellular compartments. Such methods will allow optogenetic interrogations of neurotransmission with reduced expenses/obstacles of genetic manipulations. We are developing chemical-genetic approaches to recruit photoswitchable drugs to the neuron of interest, thereby site-specifically manipulate the local receptors. We also aim to engineer genetically encoded photoswitchable modulators to bypass the need of drug treatment. Together, these approaches will enable researchers to systematically investigate neurotransmission at the molecular, cellular, and circuit levels. With the new technologies in hand, we are enthusiastic to team up with experts in neuroscience, biomedicine, advanced imaging, and engineering to unlock the mysteries of neural connectomics, synaptic plasticity, and motor control.

Dr. Lin, Wan-Chen
林宛蓁 博士

Assistant Research Fellow
助研究員

Dr. Lin, Wan-Chen 's Twitter

Ph.D. Massachusetts Institute of Technology Postdoc. University of California, Berkeley
Specialty:
  • Chemical Biology
  • Optogenetics
  • Neurotransmitter Receptors and Ion Channels

NEWS 最新消息

  1. Career Development Award

    Nov 02, 2020
  2. 2020 IBMS Research Day Award!

    Oct 15, 2020

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