Michael Zhang's Lab/Juntao Gao
Associate Professor in Bioimaging / Bioinformatics
Tsinghua National Laboratory of Information Science and Technology (TNLIST)
Room 4-203, Biotechnology Building,
Phone : 86-10-62795993
E-mail : jtgao at biomed.tsinghua.edu.cn
Education & Working Experience
· Associate professor, TNLIST, 2012 – Present
· Research Fellow, University of Illinois, 2011
· Postdoctoral Associate, Stowers Institute for Medical Research, 2006 - 2011
· Ph.D. in Bioinformatics/Bioimaging (Overall grade: CUM LAUDE), German Cancer research Center (DKFZ), University of Heidelberg, Heidelberg, Germany, 2005.
Research Area & Interests
Fig 1. Our super-resolution platform setup. Its application can be found in Zhang et al. 2016, Light Science & Application.
1. Developing super-resolution microscopy and correlative microscopy methods
Fluorescence polarization microscopy aims to detect the dipole orientation of fluorophores, but it suffers from the presence of a large number of molecules within the diffraction-limited volume, with averaged fluorescence polarization collected from a group of dipoles with different orientations. We are interested in developing new method called super-resolution dipole orientation mapping (SDOM), which resolves effective dipole orientation from a much smaller number of fluorescent molecules within a sub-diffraction focal area. We further apply this method to resolve structural details in dendritic spine neck of neuron cells, the direction of actin filaments in mammalian kidney cells and the septin hourglass structure in live yeast cells.
The revolution in the field of Electron Microscopy (EM) inspired us to develop new correlative microscopy methods, to understand more details about genome 3D structure, and how structural transition from septin hourglass to septin double ring happens in budding yeast cells.
2. Developing bioinformatics methods to understanding genome 3D structure
Fig 2. Comparison of three methods (Direction Index, HiCseg and CHDF) using 5C data, boundaries and domains around gene Sox2 and Klf4 in mouse ES cell. (Wang et al. 2015, Quantitative Biology).
The spatial organization of chromatins has played essential role in regulating transcriptional activity, and transcription, replication, and repair occur at spatially defined locations in cell nucleus. How these could be done is one of the greatest challenges in molecular biology. In our lab we are also interested in developing bioinformatics methods and visualization tools to understand genome 3D structure. We developed:
(1) Novel method, CHDF, to call Hi-C domains based on clustering (A novel method to identify topological domains using Hi-C data, Wang, Y., Li, Y., Gao, J. et al. Quant Biol (2015) 3: 81. doi:10.1007/s40484-015-0047-9, https://link.springer.com/article/10.1007/s40484-015-0047-9).
(2) Novel visualization tool HiC-3DViewer to visualize Hi-C data in 3D space (Djekidel, M.N., Wang, M., Zhang, M.Q. et al. Quant Biol (2016). doi:10.1007/s40484-017-0091-8).
(3) Novel visualization tool Web3DMol to visualize protein structure in 3D space (Shi M., Gao J., Zhang M.Q. Web3DMol: interactive protein structure visualization based on WebGL. Nucleic Acids Res 2017 gkx383. doi: 10.1093/nar/gkx383).
3. Image-based High throughput herbal drug screening
(1) Currently we are screening the potential small molecules which can target Zika virus, then will use image-based drug screening to identify potential drugs.
(2) We presented a math model, which is based on the classical Hill equation, to determine the best combination, called Fixed Dose Combination (FDC), of several natural anti-oxidants, including Vitamin C, green tea polyphenols and grape seed extract proanthocyanidin. We investigated the effects of FDC on oxidative stress, blood glucose and serum lipid levels and found that FDC determined in this investigation can become a potential solution to reduce obesity, to improve insulin sensitivity and be beneficial for the treatment of fat and diabetic patients. This work can be found in Redox Biol. 2015 Dec;6:206-17. doi: 10.1016/j.redox.2015.06.013.