Min Wu
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Research Summary
Biological systems operate away from equilibrium but the applications of non-equilibrium dynamics in our current understanding of biology remain limited. The lab of Min Wu is fascinated by cortical oscillations and travelling waves that are regulated by interacting networks of phosphoinositide-metabolizing enzymes. The laboratory is currently investigating the mechanisms of these single cell pattern formation by high-resolution quantitative imaging, optogenetics and genome-editing. We aim to employ these spatial-temporal patterns as a conceptual framework to dissect fundamental cellular processes of cell growth, cell division, and cell size control.
Extensive Research Description
Endocytic trafficking
- During my postdoctoral training, I developed a cell-free system that reconstituted clathrin-dependent budding and dynamin-dependent fission reaction from plasma membrane sheets (Wu et al., Nature Cell Biology, 2010). We showed the cooperation of two classic forms of membrane trafficking intermediates: coated vesicles and membrane tubules.
- Using a combination of cell free reconstitution, single molecule imaging and cryo-electron tomography (in collaboration with Ruben Fernandez-Busnadiego lab), my lab discovered that dynamic turnover of clathrin during the assembly phase provides a proofreading checkpoint that is essential for cargo sorting in endocytosis (Chen Y et al., JCB 2019).
Pattern formation
- We are the first to show that membrane-bending F-BAR proteins form travelling waves in cells (Wu et al., PNAS 2013). Two types of waves were observed (travelling waves and standing waves), and standing waves but not travelling waves are coupled with calcium oscillations. This unexpected observation was made in the course of investigating stimulation-dependent endocytosis, and it was motivated by findings from my cell-free reconstitution system.
- My lab later showed that these F-BAR waves are collective waves of endocytosis (Yang et al., Dev Cell 2017). These findings suggest individual budding events (namely formation of clathrin-coated pits) have non-autonomous effects that could positively feedback on each other, which lead to their partial synchronization.
Size Scaling
- Cortical oscillations arise by delayed negative feedback mechanisms. My lab demonstrated that the negative feedbacks came from SHIP1-dependent degradation of Phosphatidylinositol (3,4,5)-trisphosphate, or PIP₃. Optogenetically tuning PI3K activation could modulate oscillation frequencies, indicating the activity level of PI3K is frequency-encoded (Xiong et al., Nature Chemical Biology 2016).
- In collaboration with Jian Liu group, we proposed a curvature-dependent mechanochemical feedback model to explain the ultrafast propagation speed which is 10-100 times faster than most reaction-diffusion type of cortical waves (Wu, Su et al., Nature Communication 2018). It can be thought of as a hybrid between trigger waves and phase waves.
- If changes in oscillation periods are not coupled with those of propagation speed, wavelengths of the cortical waves could be varied by simply changing oscillation frequency. We discovered that in mitotic cells, frequencies and wavelengths of mitotic waves scaled with cell size (Xiao et al., Dev Cell, 2017). In addition, cortical waves predict site of division in metaphase, much earlier than any known spindle-dependent mechanisms.
Cell size and growth
- Do cells know their sizes during cell growth? We developed a simple PDMS channel system to investigate cell size homeostasis (how a population of cells correct for size or growth variations and maintain their uniform size distribution). We found the presence of cryptic cell size checkpoints in mammalian cells but they were not the rate-limiting step for cells to enter S-phase. Instead, they grow a constant amount during G1-phase (“adder principle”, or size-independent net growth) and reach size homeostasis in a few generations (Varsano et al., Cell Reports 2017). Our work is the first to suggest this two-tier model in mammalian cells but it echos with the classic findings in budding and fission yeasts.
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Research Interests
Organelle Biogenesis; Endocytosis; Growth; Homeostasis; Nonlinear Dynamics; Nanotechnology; Cell Shape; Wavelet Analysis; Phosphoinositide Phosphatases
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Selected Publications
- Dynamic instability of clathrin assembly provides proofreading control for endocytosis.Chen Y, Yong J, Martínez-Sánchez A, Yang Y, Wu Y, De Camilli P, Fernández-Busnadiego R, Wu M. Dynamic instability of clathrin assembly provides proofreading control for endocytosis. The Journal Of Cell Biology 2019, 218: 3200-3211. PMID: 31451612, PMCID: PMC6781453, DOI: 10.1083/jcb.201804136.
- Rhythmicity and waves in the cortex of single cells.Yang Y, Wu M. Rhythmicity and waves in the cortex of single cells. Philosophical Transactions Of The Royal Society Of London. Series B, Biological Sciences 2018, 373 PMID: 29632268, PMCID: PMC5904302, DOI: 10.1098/rstb.2017.0116.
- Membrane shape-mediated wave propagation of cortical protein dynamics.Wu Z, Su M, Tong C, Wu M, Liu J. Membrane shape-mediated wave propagation of cortical protein dynamics. Nature Communications 2018, 9: 136. PMID: 29321558, PMCID: PMC5762918, DOI: 10.1038/s41467-017-02469-1.
- Mitotic Cortical Waves Predict Future Division Sites by Encoding Positional and Size Information.Xiao S, Tong C, Yang Y, Wu M. Mitotic Cortical Waves Predict Future Division Sites by Encoding Positional and Size Information. Developmental Cell 2017, 43: 493-506.e3. PMID: 29161593, DOI: 10.1016/j.devcel.2017.10.023.
- Clathrin Assembly Defines the Onset and Geometry of Cortical Patterning.Yang Y, Xiong D, Pipathsouk A, Weiner OD, Wu M. Clathrin Assembly Defines the Onset and Geometry of Cortical Patterning. Developmental Cell 2017, 43: 507-521.e4. PMID: 29161594, PMCID: PMC5826602, DOI: 10.1016/j.devcel.2017.10.028.
- Probing Mammalian Cell Size Homeostasis by Channel-Assisted Cell Reshaping.Varsano G, Wang Y, Wu M. Probing Mammalian Cell Size Homeostasis by Channel-Assisted Cell Reshaping. Cell Reports 2017, 20: 397-410. PMID: 28700941, DOI: 10.1016/j.celrep.2017.06.057.
- Frequency and amplitude control of cortical oscillations by phosphoinositide waves.Xiong D, Xiao S, Guo S, Lin Q, Nakatsu F, Wu M. Frequency and amplitude control of cortical oscillations by phosphoinositide waves. Nature Chemical Biology 2016, 12: 159-66. PMID: 26751515, DOI: 10.1038/nchembio.2000.
- Calcium oscillations-coupled conversion of actin travelling waves to standing oscillations.Wu M, Wu X, De Camilli P. Calcium oscillations-coupled conversion of actin travelling waves to standing oscillations. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 1339-44. PMID: 23297209, PMCID: PMC3557052, DOI: 10.1073/pnas.1221538110.
- Coupling between clathrin-dependent endocytic budding and F-BAR-dependent tubulation in a cell-free system.Wu M, Huang B, Graham M, Raimondi A, Heuser JE, Zhuang X, De Camilli P. Coupling between clathrin-dependent endocytic budding and F-BAR-dependent tubulation in a cell-free system. Nature Cell Biology 2010, 12: 902-8. PMID: 20729836, PMCID: PMC3338250, DOI: 10.1038/ncb2094.
- Visualization of plasma membrane compartmentalization with patterned lipid bilayers.Wu M, Holowka D, Craighead HG, Baird B. Visualization of plasma membrane compartmentalization with patterned lipid bilayers. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 13798-803. PMID: 15356342, PMCID: PMC518836, DOI: 10.1073/pnas.0403835101.