Organism-level systems biology aims to identify, analyze, control and design cellular circuits in organisms. Many experimental and computational approaches have been developed over the years to allow us to conduct these studies. Some of the most powerful methods are based on using optical imaging in combination with fluorescent labeling, and for those one of the long-standing stumbling blocks has been tissue opacity. Recently, the solutions to this problem have started to emerge based on whole-body and whole-organ clearing techniques that employ new tissue-clearing chemistry. In this talk, I introduce these advancements and discuss how combining new clearing techniques with high performing fluorescent proteins, rapid volume imaging and efficient image informatics is resulting in comprehensive and quantitative organ-wide single-cell-resolution experimental data. These technologies are starting to yield information on connectivity and dynamics in cellular circuits at unprecedented resolution, and bring us closer to system-level understanding of physiology and diseases of complex mammalian systems.

References

1. Ueda, H.R. et al, Nature 418, 534-539 (2002).
2. Ueda, H.R. et al, Nat. Genet. 37, 187-92 (2005).
3. Sato T. K. et al, Nat Genet. 38, 312-9 (2006).
4. Ukai H. et al, Nat Cell Biol.  9, 1327-34 (2007).
5. Ukai-Tadenuma M. et al, Nat Cell Biol.  10, 1154-63 (2008).
6. Minami Y. et al PNAS 106, 9890-5 (2009).
7. Isojima Y. et al, PNAS 106, 15744-49 (2009).
8. Masumoto KH. et al, Curr Biol.20(24):2199-206.(2010).
9. Ukai-Tadenuma M et al. Cell 144(2):268-81 (2011).
10. Hogenesch JB, Ueda HR. Nature Rev. Genet. 12(6):407-16 (2011).
11. Jolley Cc, Ode KL, Ueda H.R. Cell Reports 2(4):938-50 (2012).
12. Sasagawa et al. Genome Biol. 14(4):R31 (2013).
13. Susaki et al. Cell, 157(3): 726–39, (2014).
14. Tainaka et al. Cell, 159(6):911-24(2014).
15. Susaki et al. Nature Protocols, 10(11):1709-27(2015).
16. Sunagawa et al, Cell Reports, in press (2016).
17. Susaki and Ueda. Cell Chemical Biology, in press (2016).