Dr. Lin Tian
Scientific Director Max Planck Florida Institute for Neuroscience
Adjunct Professor University of California Davis
Postdoctoral Fellow Janelia Research Campus
PhD Northwestern University
At most junctures along her career path, Dr. Lin Tian was not sure if she had what it took to make it to the next step. However, she knew that she possessed a passion for uncovering the deepest mysteries of the brain, and her colleagues and mentors recognized that she had the skill, creativity, and ingenuity to make those dreams a reality. Such lofty goals would require new technology development, but Lin was more than up to the task. Today, Lin leads the Max Planck Florida Institute for Neuroscience as its Scientific Director, and it is clear her dreams have come to fruition. From developing the first working genetically encoded calcium sensor for visualizing neuronal activity to creating sensors for neuromodulators like dopamine and serotonin, Lin has spent her career pushing boundaries – not only for herself, but also for the field of neuroscience as a whole.
After completing her undergraduate degree in Neuroscience at the University of Science and Technology of China, Lin moved to the States to pursue her PhD in Biochemistry at Northwestern University. Working with Dr. Andreas Matouschek, Lin studied the ubiquitin pathway for protein degradation. Proteasomes are best known as the cell’s garbage disposals, recognizing proteins tagged with ubiquitin for degradation. However, Lin discovered how proteasomes can also regulate transcription factors. She found that they can recognize particular regions within transcription factors, partially degrade them, and release the remaining fragments to serve new biological functions. As much as she enjoyed this work, she saw the limitations of studying proteins in isolation with western blots, and she longed to be able to visualize protein activity in real time.
This desire, combined with her persistent interest in neuroscience, led Lin to the Howard Hughes Medical Institute’s Janelia Research Campus to pursue collaborative postdoctoral research with Drs. Loren Looger, Karel Svoboda, and Luke Lavis. Her project was ambitious and sounded like something out of a science fiction novel: she sought to create a sensor for visualizing neuronal activity in living brains. At the time, sensors for calcium – the cellular influx of which strongly correlates with neuronal firing – were already in circulation, but still had significant limitations that hindered their widespread adoption by the larger neuroscience community. Synthetic indicators, like calcium-sensitive fluorescent dyes, still generally worked better (larger signals, better kinetics, etc) than available genetically encoded calcium sensors. However, genetically encoded sensors are better than synthetic indicators for longer-term and cell-type-specific imaging. Lin spearheaded the development of a new and improved genetically encoded calcium sensor, GCaMP3, and demonstrated its feasibility for imaging neuronal activity in multiple different species (worms, flies, and mice) and for long periods of times (months!). GCaMP3 thus became the first widely embraced calcium sensor and quickly revolutionized the field, ushering in a new era of in vivo imaging for cellular and systems neuroscience.
Lin still looks back fondly on her time as a postdoc – not only for the thrill of having been one of the very first people to see the activity of individual neurons in real time, but also because of the highly collaborative environment of Janelia. One of the things that drew Lin to Janelia in the first place was its “lack of walls”, and indeed, both the literal and metaphorical lack of walls had a tremendous impact on her scientific development. Lin’s three advisors all had distinct areas of expertise spanning molecular biology, neuroscience, computation, and chemistry, and she also collaborated with even more labs to demonstrate the utility of GCaMP3. She learned protein engineering, slice electrophysiology, and two-photon imaging, which were all new and challenging skills. Lin credits her time at Janelia with influencing the way she approaches science to this day – how she tackles challenging problems with “everything [she’s] got”, and how she navigates through different disciplines while being open-minded to new ideas and technologies.
During her postdoc, Lin wasn’t always certain she had what it took to become a PI. However, with growing confidence from presenting her work at conferences and finding it well received, plus some earnest encouragement from her mentors, Lin decided to apply to faculty positions. She ultimately started her lab at University of California, Davis, which she chose especially for its welcoming atmosphere. She felt supported to pursue bold ideas and develop new neuroscience tools in her lab, but also to balance this work with raising a family outside of the lab.
Lin hit the ground running as she started her new lab, “dreaming big and being fearless”. Eager to use the tools she had developed to study neuropsychiatric disorders, she initiated a project to use GCaMP to measure neuronal excitability in a human stem cell model of Down syndrome and found that altered calcium signaling in astrocytes reduced neuronal excitability. Over the next decade, she also channeled her protein engineering and tool-building background to develop novel sensors for neuromodulators, such as dopamine (“dLight”) and serotonin (“iSeroSnFR”). By developing a new sensor based on the 5-HT receptors activated by many psychedelic drugs (“psychLight”), her lab was able to screen for new compounds that are functionally similar to psychedelics and possess some of their therapeutic effects but lack hallucinogenic properties.
Inevitably, the transition from being a postdoc to starting her own lab came with some challenges. Resources had been virtually unlimited at Janelia, but that was not always the case in Lin’s own lab, especially when starting out. She also experienced a learning curve in becoming an effective mentor. She realized that what had worked for her as a trainee didn’t necessarily work for all of her trainees, and it took some time to learn how to identify people’s distinct strengths and weaknesses and develop specialized mentoring strategies for them. Inspiring and enabling others is hard, she found, but also incredibly rewarding. “I like to work with my people, to work together doing something bigger and greater.”
In the fall of 2023, Lin moved her lab to the Max Planck Florida Institute for Neuroscience to become a new Scientific Director at the institute. Lin relishes her new leadership role, especially as a woman in a position of significant scientific and institutional influence. She hopes to show young women that if she can do it, so can they. It’s a message that she might have liked to receive as a young trainee, when she encountered the various transition points in her career and wasn’t certain she could “make it” at the next stage. But now, having definitively “made it”, there is no room left for doubt. Lin’s impact on the field will go far beyond her scientific discoveries and the number of basic and clinical scientists using her tools. It will reach well into the future, encouraging the next generation of neuroscience pioneers and leaders.
Find out more about Lin and her lab’s research here.
Listen to Nancy’s full interview with Lin on August 7, 2024 below!
