(6ky) Next-Generation Fluorescence Bioimaging: Integrating Chemical and Optical Tools

Very little happens in biological processes unless two or more biomolecules come together and interact. Understanding of biomolecular dynamics in the context of the highly complex nanoscale environments are opening up the next frontier for biological discovery. However, it remains challenging to image these biomolecular assemblies, their function and interactions in structurally and dynamically complex cellular systems. Electron microscopy provides nanometer resolution but low molecular specificity. Near-field optical microscopy and atomic force microscopy are limited to imaging cell surfaces. Fluorescence microscopy offers high-specificity while the resolution is fundamentally limited to ~200-500 nm. To fill this technical void, my research will focus on the development of (1) fluorescent probes and (2) imaging methods for non-invasive nanoscale imaging tools integrating with machine-learning to understand (3) the structure and dynamics in transcriptional, translational and epigenetic processes.

Research Experience

My predoctoral training covers fluorescence spectroscopy and microscopy, organic dye synthesis, artificial molecular switches and supramolecular chemistry. Specifically, I invented photoswitchable dyes with infinite contrast for multiplexed fluorescence imaging, cancer cell detection, dynamic tracking in vivo and super-resolution imaging in live cells. Additionally, I developed ultra-bright fluorescent supramolecular nanocarriers for the intracellular delivery of guest cargo. My postdoctoral research extends to the optical implementation, imaging and processing method development for spectroscopic single-molecule localization microscopy (sSMLM).This innovative imaging technique allows high-throughput single-molecule spectroscopy in biological samples non-invasively and enables parallel, multiplexed super-resolution imaging in a single far-red detection channel. Using sSMLM, I have unraveled biomolecular dynamics in nuclear pore complexes in differentiation process and post-translational modification in programmed cell apoptosis. These research experiences allow me to fully understand the practical need in specific biological questions as well as the limitations of up-to-date dyes for super-resolution microscopy. With these practical guidelines in mind and the multidisciplinary skills in hand, I propose to develop an interdisciplinary research program to develop multidimensional nanoscale imaging tools and visualize complex molecular dynamics.

Teaching Interests:

I have gained extensive teaching and mentoring experiences in addition to my research career. I instructed 5 semesters of general chemistry lab sessions independently (for which I won an outstanding teaching award) and developed a chem-bio integrated Howard Hughes Medical Institute Initiative courses with the supervision of two professors for three semesters at the University of Miami (UM). I have also mentored 2 high-schoolers, 4 undergraduates at UM, and 4 graduate students at Northwestern University. My teaching philosophy is to promote diverse interests and curiosity of students to learn knowledges and discover the unknown. I think that students are most engaged when the learning process is fun and exciting. In addition, the ability of critical thinking is the key of learning, to develop the ability to judge where is the root to absorb the knowledge and how to apply the knowledge endlessly. My teaching interests include general chemistry and instrumentation at the undergraduate level. Additionally, I plan to develop two graduate level courses offering (1) fluorescence spectroscopy and microscopy; and (2) fundamentals and applications of artificial molecular machines.

Grant-writing experience: PI: NIGMS-R03 (pending); Subcontracting PI: NSF-CHE (CSDM-B, pending); NIGMS-K99/R00; Jane Childs Coffin Memorial Fellowship; assisting in the submissions of NIGMS-R01 (pending) and NSF-EFRI ($2M funded).

Selected Publications:

(Total number of publications = 29, First/co-first authored publications = 11)

1. Zhang, S. Swaminathan, S. Tang, J. Garcia-Amorós, M. Boulina, B. Captain, J.D. Baker, and F. M. Raymo, Photoactivatable BODIPYs Designed to Monitor the Dynamics of Supramolecular Nanocarrier. J. Am. Chem. Soc., 2015, 137, 4709–4719
2. Zhang, B. Captain and F. M. Raymo. A pH-Gated Photocage. Adv. Optical. Mater., 2016, 4, 1363-1366.
3. Zhang, S. Tang, E. Thapaliya, L. Sansalone, F.M. Raymo, Fluorescence Activation With Switchable Oxazines. Chem. Comm., 2018, 54, 8799-8809. (Front Cover)
4. Tang^#, Y. Zhang^#, P. Dhakal^#, L. Ravelo, C. L. Anderson, K. M. Collins, F. M. Raymo, Photochemical Barcodes. J. Am. Chem. Soc., 2018, 140,4485-4488. (^#Equal Author Contribution)
5. Zhang, K. Song, S. Tang, L. Ravelo, J. Cusido, C. Sun, H. F. Zhang, and F.M. Raymo, Far-Red Photoactivatable BODIPYs for the Super-Resolution Imaging of Live Cells. J. Am. Chem. Soc., 2018, 140, 12741-12745.
6. K. Song, Y. Zhang, G. Wang, C. Sun and H. F. Zhang, Three-dimensional biplane spectroscopic single-molecule localization microscopy. Optica, 2019, 6, 709-715.