Fluorescence Microscopy
fluorescence microscopy
Yao Chen, PhD
Yao Chen’s laboratory at Washington University in St. Louis is seeking a passionate Postdoctoral or staff/senior scientist/engineer who is interested in building innovative optical setups and making them useful for biological discovery. The candidate should have at least 2-3 years of experience developing optical instrumentation or microscopy methods, background in fluorescence imaging, and experience developing custom imaging software. The successful applicant will design, build, and characterize innovative optical instruments for fluorescence microscopy applications. The candidate will also have opportunities to perform optical imaging experiments and quantitative data analyses for neuroscience discovery, as well as contribute to writing research papers and grant applications. The projects in the lab aim to understand how the spatial and temporal features of signals inside the cell respond to neuromodulators (chemicals in the brain), behavior state transitions, and learning. The imaging experiments are often combined with optogenetics and electrophysiology. The candidate has access to cutting-edge instrumentation within the lab, numerous core facilities within Washington University, and will be part of a vibrant and collegial neuroscience and engineering community. We are committed to mentoring and offer a creative, thoughtful, and collaborative scientific environment. We welcome individuals who value rigor, innovation, and collegiality, and will value your creativity in shaping the projects. The lab consists of a mix of kind, fearless, and dedicated students, postdocs, and staff with diverse research and cultural backgrounds. In addition to performing their own innovative work, the candidate will have opportunities to collaborate with, learn from, and mentor other lab members. Our lab is a member of the Department of Neuroscience at Washington University School of Medicine in St. Louis, a large and collegial scientific community. WashU Neuroscience is consistently ranked as one of the top 10 places worldwide for neuroscience research. Additional information on being a postdoc at Washington University in St. Louis can be found at https://neuroscience.wustl.edu/education/postdoctoral-research/ and https://postdoc.wustl.edu/prospective-postdocs/ St. Louis is a city rich in culture, green spaces, free museums, world-class restaurants, and thriving music and arts scenes. On top of it all, St. Louis is affordable and commuting to Washington University’s campuses is stress-free, whether you go by foot, bike, public transit, or car. The area combines the attractions of a major city with affordable lifestyle opportunities. Washington University is dedicated to building a diverse community of individuals who are committed to contributing to an inclusive environment – fostering respect for all and welcoming individuals from diverse backgrounds, experiences and perspectives. Individuals with a commitment to these values are encouraged to apply. Minimum education & experience The appointee will have earned a Master’s degree (for staff scientist) or Ph.D. (for postdoctoral associate or senior scientist) by the time of starting the appointment. Applicants should submit their CV, a cover letter explaining their background and interest in the position, and whether they are applying to the scientist or postdoctoral position, as well as 3 references to Dr. Yao Chen (yaochen@wustl.edu).
CaImAn: large-scale batch and online analysis of calcium imaging data
Advances in fluorescence microscopy enable monitoring larger brain areas in-vivo with finer time resolution. The resulting data rates require reproducible analysis pipelines that are reliable, fully automated, and scalable to datasets generated over the course of months. We present CaImAn, an open-source library for calcium imaging data analysis. CaImAn provides automatic and scalable methods to address problems common to pre-processing, including motion correction, neural activity identification, and registration across different sessions of data collection. It does this while requiring minimal user intervention, with good scalability on computers ranging from laptops to high-performance computing clusters. CaImAn is suitable for two-photon and one-photon imaging, and also enables real-time analysis on streaming data. To benchmark the performance of CaImAn we collected and combined a corpus of manual annotations from multiple labelers on nine mouse two-photon datasets. We demonstrate that CaImAn achieves near-human performance in detecting locations of active neurons.
Building a synthetic cell: Understanding the clock design and function
Clock networks containing the same central architectures may vary drastically in their potential to oscillate, raising the question of what controls robustness, one of the essential functions of an oscillator. We computationally generate an atlas of oscillators and found that, while core topologies are critical for oscillations, local structures substantially modulate the degree of robustness. Strikingly, two local structures, incoherent and coherent inputs, can modify a core topology to promote and attenuate its robustness, additively. The findings underscore the importance of local modifications to the performance of the whole network. It may explain why auxiliary structures not required for oscillations are evolutionary conserved. We also extend this computational framework to search hidden network motifs for other clock functions, such as tunability that relates to the capabilities of a clock to adjust timing to external cues. Experimentally, we developed an artificial cell system in water-in-oil microemulsions, within which we reconstitute mitotic cell cycles that can perform self-sustained oscillations for 30 to 40 cycles over multiple days. The oscillation profiles, such as period, amplitude, and shape, can be quantitatively varied with the concentrations of clock regulators, energy levels, droplet sizes, and circuit design. Such innate flexibility makes it crucial to studying clock functions of tunability and stochasticity at the single-cell level. Combined with a pressure-driven multi-channel tuning setup and long-term time-lapse fluorescence microscopy, this system enables a high-throughput exploration in multi-dimension continuous parameter space and single-cell analysis of the clock dynamics and functions. We integrate this experimental platform with mathematical modeling to elucidate the topology-function relation of biological clocks. With FRET and optogenetics, we also investigate spatiotemporal cell-cycle dynamics in both homogeneous and heterogeneous microenvironments by reconstructing subcellular compartments.
Mapping of neuronal populations with light-sheet fluorescence microscopy
FENS Forum 2024
Visualization of the intact cochlea and its architecture by newly refined light sheet fluorescence microscopy
FENS Forum 2024