最近發現在麻省理工大學媒體實驗室(MIT Media Lab)的課程How to grow(almost) everything又重啟了，剛好最近在學習做合成生物學領域的實驗，所以感覺是個不錯的學習路引，一慣地野蠻學習。
How to grow(almost) everything其實是另一門How to make almost everything(假如對How to make almost everything有興趣，可參考這篇介紹文章)的生物版本課程，由哈佛大學George Church、MIT的Jacobson以及David S. Kong所開設的。幾年前也有嘗試這個課程，但那時候的理解力還不夠，且自造能力等於零，如今大概比較成熟，有基礎的自造和實驗能力和背景知識。
雖然在George Church的簡報裡面提到他實驗室的科學家Pierce J. Ogden和Eric D. Kelsic在2019年的發表，將機器學習應用於基因療法中，探討AAV病毒其外鞘蛋白序列要如何更有效率的去做突變和測試，這個方法學後來變成一間公司Dyno Therapeutics，導入於基因療法中。
from Science 29 Nov 2019:Vol. 366, Issue 6469, pp. 1139-1143
另外，我自己補充之前閱讀到的趨勢，在Carnegie Mellon University最近新成立的自動化科學Automation Science 的主任Robert F Murphy 也提到用機器學習的方法學搭配自動化高通量實驗技術。前陣子看到一篇文章也頗有趣的，利用一組數據102個可能的測試組合來做無細胞表達系統的最佳化。
from Borkowski, O., Koch, M., Zettor, A. et al. Large scale active-learning-guided exploration for in vitro protein production optimization. Nat Commun11, 1872 (2020). https://doi.org/10.1038/s41467-020-15798-5
from Ostrov, Nili, Matthieu Landon, Marc Guell, Gleb Kuznetsov, Jun Teramoto, Natalie Cervantes, Minerva Zhou, et al. 2016. “Design, Synthesis, and Testing toward a 57-Codon Genome.” Science 353 (6301): 819–22
from Larson, R.C., Maus, M.V. Recent advances and discoveries in the mechanisms and functions of CAR T cells. Nat Rev Cancer (2021). https://doi.org/10.1038/s41568-020-00323-z
from Ng, A.H.M., Khoshakhlagh, P., Rojo Arias, J.E. et al. A comprehensive library of human transcription factors for cell fate engineering. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0742-6
from Rebelo-Marques, Alexandre, Adriana De Sousa Lages, Renato Andrade, Carlos Fontes Ribeiro, Anabela Mota-Pinto, Francisco Carrilho, and João Espregueira-Mendes. 2018. “Aging Hallmarks: The Benefits of Physical Exercise.” Frontiers in Endocrinology 9 (May): 258.
Ogden, Pierce J., Eric D. Kelsic, Sam Sinai, and George M. Church. 2019. “Comprehensive AAV Capsid Fitness Landscape Reveals a Viral Gene and Enables Machine-Guided Design.” Science 366 (6469): 1139–43.
Borkowski, O., Koch, M., Zettor, A. et al. Large scale active-learning-guided exploration for in vitro protein production optimization. Nat Commun11, 1872 (2020). https://doi.org/10.1038/s41467-020-15798-5
將DNA用在資料儲存
Church, George M., Yuan Gao, and Sriram Kosuri. 2012. “Next-Generation Digital Information Storage in DNA.” Science 337 (6102): 1628.
重新編碼基因
Ostrov, Nili, Matthieu Landon, Marc Guell, Gleb Kuznetsov, Jun Teramoto, Natalie Cervantes, Minerva Zhou, et al. 2016. “Design, Synthesis, and Testing toward a 57-Codon Genome.” Science 353 (6301): 819–22.
基因和細胞療法
Liu X, Zhang Y, Cheng C, et al. CRISPR-Cas9-mediated multiplex gene editing in CAR-T cells. Cell Res. 2017;27(1):154-157. doi:10.1038/cr.2016.142
Larson, R.C., Maus, M.V. Recent advances and discoveries in the mechanisms and functions of CAR T cells. Nat Rev Cancer (2021). https://doi.org/10.1038/s41568-020-00323-z
重新調控將皮膚細胞改造成大腦
Ng, A.H.M., Khoshakhlagh, P., Rojo Arias, J.E. et al. A comprehensive library of human transcription factors for cell fate engineering. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0742-6
Niu, Dong, Hong-Jiang Wei, Lin Lin, Haydy George, Tao Wang, I-Hsiu Lee, Hong-Ye Zhao, et al. 2017. “Inactivation of Porcine Endogenous Retrovirus in Pigs Using CRISPR-Cas9.” Science 357 (6357): 1303–7.
Yang, Luhan, Marc Güell, Dong Niu, Haydy George, Emal Lesha, Dennis Grishin, John Aach, et al. 2015. “Genome-Wide Inactivation of Porcine Endogenous Retroviruses (PERVs).” Science 350 (6264): 1101–4.
Yang, Siyoung, Noriyuki Fujikado, Dmitriy Kolodin, Christophe Benoist, and Diane Mathis. 2015. “Immune Tolerance. Regulatory T Cells Generated Early in Life Play a Distinct Role in Maintaining Self-Tolerance.” Science 348 (6234): 589–94.
抗老化
Khosla, Sundeep, Joshua N. Farr, Tamara Tchkonia, and James L. Kirkland. 2020. “The Role of Cellular Senescence in Ageing and Endocrine Disease.” Nature Reviews. Endocrinology 16 (5): 263–75.
Kruempel, Joseph C. P., Marshall B. Howington, and Scott F. Leiser. 2019. “Computational Tools for Geroscience.” Translational Medicine of Aging 3 (November): 132–43.
Magalhães, João Pedro de, and Olivier Toussaint. 2004. “GenAge: A Genomic and Proteomic Network Map of Human Ageing.” FEBS Letters 571 (1-3): 243–47.
Melzer, David, Luke C. Pilling, and Luigi Ferrucci. 2020. “The Genetics of Human Ageing.” Nature Reviews. Genetics 21 (2): 88–101.
Partridge, Linda, Matias Fuentealba, and Brian K. Kennedy. 2020. “The Quest to Slow Ageing through Drug Discovery.” Nature Reviews. Drug Discovery 19 (8): 513–32.
Rebelo-Marques, Alexandre, Adriana De Sousa Lages, Renato Andrade, Carlos Fontes Ribeiro, Anabela Mota-Pinto, Francisco Carrilho, and João Espregueira-Mendes. 2018. “Aging Hallmarks: The Benefits of Physical Exercise.” Frontiers in Endocrinology 9 (May): 258.
Rijt, Sanne van der, Marte Molenaars, Rebecca L. McIntyre, Georges E. Janssens, and Riekelt H. Houtkooper. 2020. “Integrating the Hallmarks of Aging Throughout the Tree of Life: A Focus on Mitochondrial Dysfunction.” Frontiers in Cell and Developmental Biology 8 (November): 594416.
Tacutu, Robi, Daniel Thornton, Emily Johnson, Arie Budovsky, Diogo Barardo, Thomas Craig, Eugene Diana, et al. 2018. “Human Ageing Genomic Resources: New and Updated Databases.” Nucleic Acids Research 46 (D1): D1083–90.
這篇是分享閱讀Paul Graham十一月的文章How to Think For Yourself。沒聽過Paul Graham的人也可以趁機了解一下，他算是矽谷創業圈的老前輩，創辦的Y Combinator是目前很重要的一個美國新創孵育器。他本身會把自己的小散文貼在一個簡單的網站來分享，文字都相當的淺顯和易懂，看得出來是非常厲害的寫手。
這篇文章How to Think For Yourself，其實想表達的東西很簡單，如何成為一個獨立思考的人，以及怎樣的特質能保持獨立思考的特性(Independent-mindedness)，文中很簡單地提到三個重要的特點，且彼此可以互相加強：
這邊有幾個範例，來體會一下如何把字句更加地讓人易理解，下面是一個節錄自The Journal of Clinical Oncology的開頭：
Adoptive cell transfer (ACT) immunotherapy is based on the ex vivo selection of tumor-reactive lymphocytes, and their activation and numerical expression before reinfusion to the autologous tumor-bearing host
These findings imply that the rates of ascorbate radical production and its recycling via dehydroascorbate reductase to replenish the ascorbate pool are equivalent at the lower irradiance, but not equivalent at higher irradiance with the rate of ascorbate radical production exceeding its recycling back to ascorbate"
修改過後如下，整體的可讀性增加，更容易理解且順暢。
These findings imply that, at low irradiation, ascorbate radicals are produced and recycled at the same rate, but at high irradiation, they are produced faster than they can be recycled back to ascorbate
如何寫的簡白(Effective Writing)的三個要點
減少不必要且意義模糊的用字原則(Cut the clutter)
主動語氣
使用洽當的動詞
盡可能減少多餘的字，你永遠都會驚訝於能使用更少的字來表達同樣的道理：
範例一
This paper provides a review of the basic tenets of cancer biology study design, using as examples studies that illustrate the methodologic challenges or that demonstrate successful solutions to the difficulties inherent in biology result.
This paper provides a review of the basic tenets of cancer biology study design, using as examples studies that illustrate the methodologic challenges or that demonstrate successful solutions to the difficulties inherent in biology result. [高手改]
範例二
As it is well known, increased athletic activity has been related to a profile of lower cardiovascular risk, lower blood pressure levels, and improved muscular and cardio-respiratory performance
Increased athletic activity is known to lower cardiovascular risk and pressure levels, and improved muscular and cardio-respiratory performance[土炮練習]
Increased athletic activity is associated with lower cardiovascular risk, lower blood pressure, and improved fitness. [高手改的]
範例三
The experimental demonstration is the first of its kind and is a proof of principle for the concept of laser driven particle acceleration in a structure loaded vacuum
The experiments demonstrate the proof of concept that laser-driven particle can accelerate in the structure loaded vacuum. [土炮練習]
The experiment provides the first of principle of laser-driven particle acceleration in a structure-loaded vacuum.[高手改]
範例四
Brain injury incidence shows two peak periods in almost all reports: rates are the highest in young people and the elderly
Brain injury incidence peaks in young and the elderly [高手改]
圖片來自Science雜誌的文章 Community science: Not just a hobby
在2019年8月刊登在科學雜誌的文章：社區科學-不只是興趣，裡面提到以麻省理工學院多媒體實驗室主辦的Global Community Bio Summit ，描述這一個新興的趨勢，把以往只鎖在學術殿堂裡的生物技術、基因工程、合成生物學打開成全民可參與的一個舞台，麻省理工學院社群生命科學技術計畫的負責人David Kong描述這個希望能進一步打造全球生命科學熱愛者社群的努力，這個社群其實本身就是非常多樣性，其中有DIY Biologist、Community Biologist、Biohackers、Biomakers等等，每年一次的會議將這群人聚集一起互相分享，這邊是他們2019年的議程，可以由此一窺他們都在討論些甚麼。
基因泰克：生物科技的起源（Genentech: The Beginnings of Biotech）
這本書發表於2012年，其內容在講基因泰克公司的故事，這間公司在生醫領域幾乎沒有人不知道，時至如今已經是行業裡的巨頭，很難想像他們在1976年左右是如何從零開始的。而這本書撰寫的就是從Robert A. Swanson和Herbert Boyer教授兩人公司到上市這段時間的胼手便足，閱讀的時候很難想像那時候的氛圍，從今天的角度會認為頂尖大學教授創辦生技公司很正面(在台灣可能還沒有那麼正面，往往都會從自肥的角度來看)，但實際上在30幾年前對於科學家們還很難接受這件事。
Poritz, Mark A., Anne J. Blaschke, Carrie L. Byington, Lindsay Meyers, Kody Nilsson, David E. Jones, Stephanie A. Thatcher, et al. 2011. “FilmArray, an Automated Nested Multiplex PCR System for Multi-Pathogen Detection: Development and Application to Respiratory Tract Infection.” PloS One 6 (10): e26047.
Messacar K, et al. Potential clinical impact of the filmarray meningitis encephalitis panel in children with suspected central nervous system infections. Diagn Microbiol Infect Dis. 2016 Sep;86(1):118-20.
又挑了一本牛津出版社A Very Short Introduction的書來閱讀，此本是針對合成生物學(Synthetic biology)的入門簡介，作者傑米.戴維斯(Jamie A. Davies)為愛丁堡大學實驗姐頗學教授，本身的研究專注在使用合成生物學工具來理解胚胎發育和組織工程的應用，其還有一本再談胚胎發育的科普書Life Unfolding。
我們的基因體時代 Our "Gene"ration 