研究介紹
細胞生長是生物系統存續的基礎，由細胞內的代謝網絡所支持。為達成高效生長，細胞必須在生物合成與能量消耗間維持均衡。當環境改變時，細胞也會重新調整生長跟代謝以保持生理恆定 (homeostasis)。我們使用實驗，計算模擬和理論的方式來研究生長與代謝的動態變化：
單細胞尺度的代謝動態
測量代謝物的實時動態在實驗上富有挑戰性。我們結合了微流體培養，生物傳感器 (biosensors)，螢光顯微技術與定量影像分析來進行研究。我們發現腺苷三磷酸 (ATP) 的濃度在大腸桿菌中是隨細胞週期變化的，而其週期性的動態還依賴於乙酸發酵 (Lin and Jacobs-Wagner, 2022)。在單細胞尺度下，我們發現 ATP 的變動幅度和細胞生長呈負相關；這也指出了代謝恆定的重要性。未來，我們將探索在基因體擾動與養分變化下各種代謝物的動態調控。我們也有興趣研究微生物群集內細胞互動對代謝的影響。
三腺苷磷酸 (ATP) 在大腸桿菌的實時測量。細胞在微流體線形器材中排成一列。彩圖中每直列代表一個時間點，不同顏色對應不同 ATP 的濃度。在正常指數生長的狀況下，ATP 的濃度在 1 mM 與4 mM 間震蕩變化。
反應網絡與自催化系統的數學模型
生物系統往往是非線性且遠離平衡態的。了解系統生長與擴張的自然規律是系統生物學、生物物理與生物數學等多個領域的共同目標。使用可縮放流函數 (scalable flux function) 與反應網絡為基礎，我們發展了一個理論框架，並分析了一整類的指數生長系統。我們將古典的均衡生長模型延伸到包含震蕩甚至混沌的生長模式 (Lin et. al., 2020)。未來我們將使用不同領域的概念來分析自催化系統，包括遍歷理論，時延系統，非平衡物理等。
人員招聘
我們實驗室計畫招募博士後研究員，博士班學生，碩士班學生以及研究助理。請參考以下連結或直接與老師email聯繫！ (博士後研究員,研究助理)
- Postdoc researcher, 2021-2023, Stanford University
- Postdoc researcher, 2016-2020, Yale University
- PhD in Biology, 2008-2015, New York University
- Bachelors in Life Science/Physics (double major), 2002-2007, National Taiwan University
- Connecting single-cell ATP dynamics to overflow metabolism, cell growth and the cell cycle in Escherichia coli. Wei-Hsiang Lin and Christine Jacobs-Wagner (2022) Current Biology 32(18):3911-3924
- Origin of exponential growth in nonlinear reaction networks. Wei-Hsiang Lin*, Edo Kussell, Lai-Sang Young and Christine Jacobs-Wagner* (2020) Proceedings of the National Academy of Sciences 117 (45), 27795-27804 (*: Co-correspondent author)
- Complex interplay of physiology and selection in the emergence of antibiotic resistance. Wei-Hsiang Lin and Edo Kussell (2016) Current Biology 26(11):1486-1493
- Populations adapt to fluctuating selection using derived and ancestral allelic diversity. Wei-Hsiang Lin, Mark J. Rocco, Amelia Bertozzi-Villa, Edo Kussell (2015) Evolution 69(6):1448-1460
- Evolutionary pressures on simple sequence repeats in prokaryotic coding regions. Wei-Hsiang Lin and Edo Kussell. (2012) Nucleic Acid Research 40(6):2399-2413
- Nak regulates localization of clathrin sites in higher-order dendrites to promote local dendrite growth. Wei-Kang Yang, Yu-Huei Peng, Hsun Li, Hsiu-Chen Lin, Yu-Ching Lin, Tzu-Ting Lai, Hsien Suo, Chien-Hsiang Wang, Wei-Hsiang Lin, Chan-Yen Ou, Xin Zhou, Haiwei Pi, Henry C. Chang and Cheng-Ting Chien 12 (2011) Neuron. 72(2):285-299
- CSN-mediated deneddylation differentially modulates Ci155 proteolysis to promote Hedgehog signaling responses. June-Tai Wu, Wei-Hsiang Lin, Wei-Yu Chen, Yi-Chun Huang, Chiou-Yang Tang, Margaret S. Ho, Haiwei Pi & Cheng-Ting Chien (2011) Nature Communications 2(1):1-9
- Nak regulates Dlg basal localization in Drosophila salivary gland cells. Yu-Huei Peng, Wei-Kan Yang, Wei-Hsiang Lin, Tzu-Ting Lai and Cheng-Ting Chien (2009) Biochem Biophys Res Commun., 382(1):108-113.
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Principal investigator Wei-Hsiang Lin (林暐翔) |
Single-cell metabolism, microfluidic culture, Autocatalytic theory in dynamical system. |
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Postdoctoral associate Nathan Muyinda (穆英達) |
Theoretical ecology on species coexistence dynamics, intransitive competition, and community growth. |
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Master’s level research assistant Agatha Cecila Sihite (西莉亞) |
Studying cell growth and energetics response under metabolic perturbation. |
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Master's level research assistant Udhaya Bala Kanna (吳德亞) |
Studying acetate fermentation and cellular physiology with fluorescence biosensors. |
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Master's level research assistant Hsin-Yao Feng (馮信堯) |
Agent-based modeling in metabolic and population dynamics. |
Updated on 2024 Mar.
