Syukuro Manabe demonstrated how increased levels of carbon dioxide in the atmosphere lead to increased temperatures at the surface of the Earth.
Klaus Hasselmann created a model that links together weather and climate, thus answering the question of why climate models can be reliable despite weather being changeable and chaotic.
Giorgio Parisi discovered hidden patterns in disordered complex materials. His discoveries are among the most important contributions to the theory of complex systems. They make it possible to understand and describe many different and apparently entirely random materials and phenomena, not only in physics but also in other, very different areas, such as mathematics, biology, neuroscience and machine learning.
David Julius – awarded this year’s #NobelPrize in Physiology or Medicine – utilised capsaicin, a pungent compound from chilli peppers that induces a burning sensation, to identify a sensor in the nerve endings of the skin that responds to heat. pic.twitter.com/GInY2q6RlD
2021 #NobelPrize laureate in physiology or medicine Ardem Patapoutian used pressure-sensitive cells to discover a novel class of sensors that respond to mechanical stimuli in the skin and internal organs. pic.twitter.com/6T7661lRPq
「フォース」を感知するタンパク質を求めて Nature ダイジェスト Vol. 17 No. 4 | doi : 10.1038/ndigest.2020.200418 原文：Nature (2020-01-09) | doi: 10.1038/d41586-019-03955-w | The quest to decipher how the body’s cells sense touch
ノーベル賞につづく可能性が高いとされるラスカー賞ですが、2021年ラスカー賞はCOVID-19のmRNAワクチンの開発者Katalin Kariko博士（BioNTech）とDrew Weissman博士（University of Pennsylvania）に贈られました。新型コロナウイルスがまだ終息していない今の段階でのノーベル賞受賞はないだろうと思いますが、彼らがノーベル賞を取るのは時間の問題ではないかと思います。
昨日のノーベル医学生理学賞に続き、今日はノーベル物理学賞の受賞者が発表されました。2020年ノーベル物理学賞はRoger Penrose, Reinhard Genzel, Andrea Ghezの3氏に授与されます。
The Nobel Prize in Physics 2020 was divided, one half awarded to Roger Penrose “for the discovery that black hole formationis a robust prediction of the general theory of relativity“, the other half jointly to Reinhard Genzel and Andrea Ghez “for the discovery of a supermassive compact object at the centre of our galaxy.” (https://www.nobelprize.org/prizes/physics/2020/summary/)
The Nobel Assembly at Karolinska Institutet has today decided to award the 2020 Nobel Prize in Physiology or Medicine jointly to Harvey J. Alter, Michael Houghton and Charles M. Rice for the discovery of Hepatitis C virus (nobelprizemedicine.org)
ノーベル賞受賞理由: C型肝炎ウイルスの発見
Harvey J. Alter, Michael Houghton and Charles M. Rice made seminal discoveries that led to the identification of a novel virus, Hepatitis C virus. Prior to their work, the discovery of the Hepatitis A and B viruses had been critical steps forward, but the majority of blood-borne hepatitis cases remained unexplained. The discovery of Hepatitis C virus revealed the cause of the remaining cases of chronic hepatitis and made possible blood tests and new medicines that have saved millions of lives. (pm_eng_FINAL_2020.pdf)
肝炎を引き起こすウイルスの種類
There are two main forms of hepatitis. One form is an acute disease caused by Hepatitis A virus that is transmitted by contaminated water or food. The other form is caused by Hepatitis B virus or Hepatitis C virus (this year’s Nobel Prize). This form of blood-borne hepatitis is often a chronic disease that may progress to cirrhosis and hepatocellular carcinoma. (pm_eng_FINAL_2020.pdf)
非A型、非B型肝炎ウイルスの存在を示したハービー・アルターの研究
At that time, Harvey J. Alter at the US National Institutes of Health was studying the occurrence of hepatitis in patients who had received blood transfusions. Although blood tests for the newly-discovered Hepatitis B virus reduced the number of cases of transfusion-related hepatitis, Alter and colleagues worryingly demonstrated that a large number of cases remained. Tests for Hepatitis A virus infection were also developed around this time, and it became clear that Hepatitis A was not the cause of these unexplained cases. It was a great source of concern that a significant number of those receiving blood transfusions developed chronic hepatitis due to an unknown infectious agent. Alter and his colleagues showed that blood from these hepatitis patients could transmit the disease to chimpanzees, the only susceptible host besides humans. Subsequent studies also demonstrated that the unknown infectious agent had the characteristics of a virus. Alter’s methodical investigations had in this way defined a new, distinct form of chronic viral hepatitis. The mysterious illness became known as “non-A, non-B” hepatitis. (pm_eng_FINAL_2020.pdf)
C型肝炎ウイルスを発見したマイケル・ホートンの実験:未知のウイルスのゲノム断片の同定
Michael Houghton, working for the pharmaceutical firm Chiron, undertook the arduous work needed to isolate the genetic sequence of the virus. Houghton and his co-workers created a collection of DNA fragments from nucleic acids found in the blood of an infected chimpanzee. The majority of these fragments came from the genome of the chimpanzee itself, but the researchers predicted that some would be derived from the unknown virus. On the assumption that antibodies against the virus would be present in blood taken from hepatitis patients, the investigators used patient sera to identify cloned viral DNA fragments encoding viral proteins. Following a comprehensive search, one positive clone was found. (pm_eng_FINAL_2020.pdf)
C型肝炎ウイルスが実際に肝炎の原因となることを証明したチャールズ・ライスの実験
Charles M. Rice, a researcher at Washington University in St. Louis, along with other groups working with RNA viruses, noted a previously uncharacterized region in the end of the Hepatitis C virus genome that they suspected could be important for virus replication. Rice also observed genetic variations in isolated virus samples and hypothesized that some of them might hinder virus replication. Through genetic engineering, Rice generated an RNA variant of Hepatitis C virus that included the newly defined region of the viral genome and was devoid of the inactivating genetic variations. When this RNA was injected into the liver of chimpanzees, virus was detected in the blood and pathological changes resembling those seen in humans with the chronic disease were observed. (pm_eng_FINAL_2020.pdf)
The Nobel Assembly at Karolinska Institutet has today decided to award the 2019 Nobel Prize in Physiology or Medicine jointly to William G. Kaelin, Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza. for their discoveries of how cells sense and adapt to oxygen availability (PDF)
２０１９年ノーベル医学生理学賞発表の瞬間
Announcement of the Nobel Prize in Physiology or Medicine 2019 Nobel Prize
Sir Peter J. Ratcliffe
ノーベル賞受賞直後のピーター・ラトクリフ氏の電話インタビュー
ピーター・ラトクリフ博士の講演動画。
Elucidation of oxygen sensing pathways in human and animal cells // Peter Ratcliffe 2018/09/28 The Physiological Society
William G. Kaelin
ウィリアム・ケリンのレクチャー動画。
Signaling Pathways in Cancer Symposium: William Kaelin 2016/08/11 KochInstituteMIT
Gregg Semenza
グレッグ・セメンザ（Gregg Semenza）が語る研究者の日常、研究はいかに進むか。
Gregg Semenza on the discovery of HIF-1
下の動画は、生い立ちから研究の話までのロング・インタビュー。
JCI’s Conversations with Giants in Medicine: Gregg Semenza 2016/11/02 Journal of Clinical Investigation
本庶氏、妥協許さず厳しい指導 「疑問にこだわれ」口癖 （日本経済新聞 2018/10/1 21:54）科学者に贈られる至高の賞に輝いた本庶佑さんは「疑問にこだわれ」が口癖。… 父や叔父、祖父も医師で京都大医学部に進む。入学後、遺伝子組み換え技術の可能性を示した「生物学の革命」（柴谷篤弘著）に刺激を受けて研究者の道を志した。学部生時代から、日本の生化学を切り開いた京大の早石修博士の研究室に出入りし、研究者としての基礎を学んだ。研究では厳しい指導でも知られた。「とにかく厳しい。弟子はみな『一日も早く辞めたい』と思っていた」。大阪大大学院教授の仲野徹さん（61）は、京大医学部で本庶さんの助手を務めていた25年ほど前を振り返って笑う。本庶さんの口癖は「Stick to the question！（疑問にこだわれ）」。他人の理論に注意を向けるのではなく、自分自身が設定した問題に集中するように口酸っぱく説いたという。「とにかく一つ一つの事象を厳しくチェックされる。社会のためになる研究かどうかを追求し、求められるレベルも非常に高かった」 研究を離れると厳しさとは違った一面も。「面倒見がよく、弟子から慕われる存在だった」（仲野さん）京大の研究室で指導を受けた奈良先端科学技術大学院大准教授の石田靖雅さんも「極めて才能豊かで重要な部分を指摘してもらった。研究に対する集中力は爆発的で、すごいエネルギーだ」と振り返る。妥協を許さず指導する姿が印象的だったという。
BREAKING NEWS
The 2018 #NobelPrize in Physiology or Medicine has been awarded jointly to James P. Allison and Tasuku Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation.” pic.twitter.com/gk69W1ZLNI
Cancer kills millions of people every year and is one of humanity’s greatest health challenges. By stimulating the ability of our immune system to attack tumour cells, this year’s #NobelPrize laureates have established an entirely new principle for cancer therapy. pic.twitter.com/6HJWsXw4bE
Tasuku Honjo, awarded the 2018 #NobelPrize, discovered a protein on immune cells and revealed that it also operates as a brake, but with a different mechanism of action. Therapies based on his discovery proved to be strikingly effective in the fight against cancer. pic.twitter.com/3yn2RCtr6W
Harz & Hegemann 1991 Nature
Nagel et al., 2002
Nagel et al., 2003
Kato et al., 2012
Wieteck et al., 2014 Science with M. Elstner
Wietek et al., 2015 Scientific Rep (collaboration)
In conversation with Prof. Peter Hegemann. Institute of Molecular Cell & Systems Biology UofG YOUTUBE（音声のみ 44:54）2018/02/23 に公開 He spoke with us about how to be persistent in your research, and how to play the long game of building a career through the highs and lows of the scientific process. 研究生活、論文出版の悲喜こもごも、ホンネが語られていて興味深い。
カール・ダイセロス博士
カール・ダイセロス博士によるオプトジェネティクス概論
Karl Deisseroth (Stanford / HHMI): Development of Optogenetics
エド・ボイデン博士
エド・ボイデン博士(CV)によるオプトジェネティクスの概論
Ed Boyden on Optogenetics — selective brain stimulation with light
Han and Boyden 2007 PLoS ONE 2(3):e299
Chow, Han, et al., 2010. Nature 463:98-102
オプトジェネティクス研究の歴史 開発者によるレビュー論文
A history of optogenetics: the development of tools for controlling brain circuits with light Edward S. Boyden F1000 Biol Rep. 2011; 3: 11. Published online 2011 May 3
There’s only one problem with this story: It just may be that Zhuo-Hua Pan invented optogenetics first. Even many neuroscientists have never heard of Pan. Pan, 60, is a vision scientist at Wayne State University in Detroit who began his research career in his home country of China. (He may have invented one of neuroscience’s biggest advances. But you’ve never heard of him By ANNA VLASITS SEPTEMBER 1, 2016 STATNEWS)
Pan presented his work at a conference in 2005, a few months before Boyden and Deisseroth published their paper. But Pan struggled to get his work published in a journal until a year later. (The History of Optogenetics Revised Credit for the neuroscience technique has largely overlooked the researcher who first demonstrated the method. Sep 1, 2016 KERRY GRENS, TheScientist)
Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Bi A, Cui J, Ma YP, Olshevskaya E, Pu M, Dizhoor AM, Pan ZH. Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. Neuron. 2006 Apr 6;50(1):23-33.
Optogenetics: Applications in psychiatric research Fukutoshi Shirai MSc Akiko Hayashi‐Takagi MD, PhD PCN Frontier Review First published: 24 February 2017
参考
Optogenetics (ENCYCLOPAEDIA BRITANNICA WRITTEN BY: Karl Deisseroth LAST UPDATED: Sep 10, 2018)
2020年10月7日のノーベル財団の発表によりますと、2020年のノーベル化学賞が、Jennifer A. Doudna(ジェニファー・ダウドナ)、 Emmanuel Charpentier(エマニュエル・シャルパンティエ)の両氏に与えられることになりました。
Announcement of the 2020 Nobel Prize in Chemistry Nobel Prize
祝☆ノーベル化学賞2020
ノーベル賞の枠は3人。CRISPR/Cas9の有用性は直ちに認識されて熾烈な特許戦争が勃発していたわけですが、Jennifer A. Doudna(ジェニファー・ダウドナ)、 Emmanuel Charpentier(エマニュエル・シャルパンティエ)の二人がノーベル賞3人枠の中に入ることは、誰の目にも明らかでした。ノーベル賞をもらって当然と言われてきましたが、それでも、実際に本当に授賞が決まるとこれほど嬉しいものなんだなあとこの映像を見ていて思いました。
First Day in a Nobel Life: Jennifer Doudna 2020/10/07 UC Berkeley
大阪大学微生物病研究所の研究グループが奇妙な繰り返し配列を大腸菌のゲノムで見つけ、石野 良純（いしの よしずみ)博士らが1987年に論文報告をしたのが、CRISPRが見出された最初の例です。この配列は、後の研究者によって、CRISPR、Clustered Regularly Interspaced Short Palindromic Repeatsと名付けられることになります。
Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A. (1987). Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol 169: 5429-5433. PDFリンク
FIG. 5. Comparison of direct-repeat sequences consisting of 61 base pairs in the 3′-end flanking region of iap. The 29 highly conserved nucleotides, which contain a dyad symmetry of 14 base pairs (underlined), are shown at the bottom. Homologous nucleotides found in at least two DNA segments are shown in boldface type. The second translational termination codon is boxed. The nucleotide numbers are in parentheses.
An unusual structure was found in the 3′-end flanking region of iap (Fig. 5). Five highly homologous sequences of 29 nucleotides were arranged as direct repeats with 32 nucleotides as spacing. The first sequence was included in the putative transcriptional termination site and had less homology than the others. Well-conserved nucleotide sequences containing a dyad symmetry, named REP sequences, have been found in E. coli and Salmonella typhimurium (28) and may act to stabilize mRNA (18). A dyad symmetry with 14 nucleotide pairs was also found in the middle of these sequences (underlining, Fig. 5), but no homology was found between these sequences and the REP sequence. So far, no sequence homologous to these has been found elsewhere in procaryotes, and the biological significance of these sequences is not known.
この論文では、「現在のところ、今回見つかった配列と相同性を示す配列は他の原核生物では見つかっていない。また、この配列の生物学的な意義は不明である（So far, no sequence homologous to these has been found elsewhere in procaryotes, and the biological significance of these sequences is not known）」と述べています。
Mojica, F.J.M., Dıez-Villasenor, C., Soria, E., and Juez, G. (2000). Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. Mol. Microbiol. 36, 244–246. HTMLリンク
The question emerges here as to whether the SRSRs have a common function in prokaryotes, or whether their presence is reminiscent of ancient sequences and their role diverged with evolution. The universality, phylogeny and biological significance of this peculiar family of repeats arises as an item to be elucidated. (Mojica eta l., 2000 結論のセクションより)
Identification of genes that are associated with DNA repeats in prokaryotes. Jansen R, Embden JD, Gaastra W, Schouls LM. Mol Microbiol. 2002 Mar;43(6):1565-75. PDF link
To appreciate their characteri-stic structure, we will refer to this family as the clustered regularly interspaced short palindromic repeats (CRISPR). In most species with two or more CRISPR loci, these loci were flanked on one side by a common leader sequence of 300-500 b. （中略）Four CRISPR-associated (cas) genes were identified in CRISPR-containing prokaryotes that were absent from CRISPR-negative prokaryotes. The cas genes were invariably located adjacent to a CRISPR locus, indicating that the cas genes and CRISPR loci have a functional relationship. The cas3 gene showed motifs characteristic for helicases of the superfamily 2, and the cas4 gene showed motifs of the RecB family of exonucleases, suggesting that these genes are involved in DNA metabolism or gene expression. （Jansen et al., Mol Microbiol. 2002 Mar;43(6):1565-75.の論文の要旨から一部抜粋)
The finding in this study that the CRISPR loci were strictly associated with a set of homologous genes, one of which has nucleic acid helicase motifs (the Cas3 homologues), one of which has exonuclease activity (the Cas4 homologues) and one of which has a high pI (the CasI homologues), as is often found for DNA-binding proteins, may be suggestive of a role for the Cas proteins in the genesis of CRISPR loci. (Jansen et al., Mol Microbiol. 2002 Mar;43(6):1565-75.の論文の議論のセクションから抜粋)
CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies. C. Pourcel, G. Salvignol, G. Vergnaud. First Published Online: 01 March 2005, Microbiology 151: 653-663. HTML link
One possible explanation for that finding could be that CRISPRs are structures able to take up pieces of foreign DNA as part of a defence mechanism. In this view, it is tempting to further speculate that CRISPRs may represent a memory of past ‘genetic aggressions’. The fact that most of the spacers described in other bacteria have no homologue in the databases could still be explained by such a phage origin, as only a very small number of the existing bacteriophages have so far been sequenced. (Pourcel et al., Microbiology 151: 653-663. ディスカッションセクションより抜粋)
Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Bolotin A, Quinquis B, Sorokin A, Ehrlich SD. Microbiology. 2005 Aug;151(Pt 8):2551-61. HTML link
Here we report a correlation between the number of spacers in a locus and the resistance of S. thermophilus to phage infection, suggesting that CRISPRs can have a different biological role, protecting the bacteria against phage attack. (Bolotin et al., Microbiology 151(Pt 8):2551-61)
CRISPR provides acquired resistance against viruses in prokaryotes. Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, Romero DA, Horvath P. Science 2007 Mar 23;315(5819):1709-12.
Clustered regularly interspaced short palindromic repeats (CRISPR) are a distinctive feature of the genomes of most Bacteria and Archaea and are thought to be involved in resistance to bacteriophages. We found that, after viral challenge, bacteria integrated new spacers derived from phage genomic sequences. Removal or addition of particular spacers modified the phage-resistance phenotype of the cell. Thus, CRISPR, together with associated cas genes, provided resistance against phages, and resistance specificity is determined by spacer-phage sequence similarity. (Barrangou et al., 2007 要旨）
Cas9–crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria.Giedrius Gasiunas, Rodolphe Barrangou, Philippe Horvath, and Virginijus Siksnys. PNAS September 25, 2012 109 (39) E2579-E2586; https://doi.org/10.1073/pnas.1208507109
Here, we demonstrate that the Cas9–crRNA complex of the Streptococcus thermophilusCRISPR3/Cas system introduces in vitro a double-strand break at a specific site in DNA containing a sequence complementary to crRNA. DNA cleavage is executed by Cas9, which uses two distinct active sites, RuvC and HNH, to generate site-specific nicks on opposite DNA strands. Results demonstrate that the Cas9–crRNA complex functions as an RNA-guided endonuclease with RNA-directed target sequence recognition and protein-mediated DNA cleavage. （要旨より一部抜粋）
A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. Science. 2012 Aug 17;337(6096):816-21.
We propose an alternative methodology based on RNA-programmed Cas9 that could offer considerable potential for gene-targeting and genome-editing applications. (Jinek et al., 2012)
George Church博士やFeng Zhang博士の研究グループにより、CRISPR/Cas9システムが真核生物においても働くことが示され、ゲノム編集ツールとして人間を含めた全ての真核生物に応用する道が開かれました。
RNA-Guided Human Genome Engineering via Cas9. Prashant Mali, Luhan Yang, Kevin M. Esvelt, John Aach, Marc Guell, James E. DiCarlo, Julie E. Norville, George M. Church. Science 15 Feb 2013; Vol. 339, Issue 6121, pp. 823-826
The fully defined nature of this two-component system suggested that it might function in the cells of eukaryotic organisms such as yeast, plants, and even mammals. By cleaving genomic sequences targeted by RNA sequences (4–6), such a system could greatly enhance the ease of genome engineering. (Mali et al., 2013 のイントロダクションより。太字強調は当サイト）
Multiplex Genome Engineering Using CRISPR/Cas Systems. Le Cong, F. Ann Ran, David Cox, Shuailiang Lin, Robert Barretto, Naomi Habib, Patrick D. Hsu, Xuebing Wu, Wenyan Jiang, Luciano A. Marraffini, Feng Zhang.Science 15 Feb 2013:Vol. 339, Issue 6121, pp. 819-823
KS Community Lecture: Genome Editing Using CRISPR-Cas Systems
フェン・ジャン（Feng Zhang）博士による解説
Development and Applications of CRISPR-Cas9 for Genome Engineering. Patrick D.Hsu, Eric S.Lander, Feng Zhang. Cell Volume 157, Issue 6, 5 June 2014, Pages 1262-1278 HTML link
Zhang studied chemistry and physics at Harvard and graduated with the highest honors. He then headed to Stanford University for his doctoral work, where he joined the newly formed lab of Karl Deisseroth, who had just begun to develop optogenetics as a method for manipulating brain activity. Over the next five years, Zhang played a central role in making optogenetics a reality.
In 2009, after earning a PhD in chemistry, Zhang switched his focus to genome editing. That same year, he received a prestigious three-year Harvard Junior Fellowship, during which he worked in the laboratories of two Harvard Medical School professors, Paola Arlotta and George Church. There, he helped develop a new method of gene editing through the adaptation of TAL effectors (TALEs), sequence-specific DNA-binding proteins found in plant pathogens that alter gene expression in plants.
Biology and Applications of CRISPR Systems: Harnessing Nature’s Toolbox for Genome Engineering. Addison V.Wright, James K.Nuñez, Jennifer A.Doudna. Cell Volume 164, Issues 1–2, 14 January 2016, Pages 29-44. PDF link
Jennifer Doudna: CRISPR Basics （2017 CRISPR Workshop YOUTUBE動画 Innovative Genomics Institute – IGI 2017/11/04）
gRNA: guide RNA (sgRNA (single-strand guide RNA, single guide RNA, short guide RNA)とも表記） 自然界では複合体を形成して働くcrRNAとtracrRNAを、ゲノム編集ツールとして利用しやすいよう、人工的にひと続きのRNAにしたもの。
Cascade: CRISPR-Associated Complex for Antiviral Defense (Brouns et al., 2008 Science) タンパク質からなる巨大な複合体で内部にCRISPR配列のRNA転写物があり、これを使って感染によるウイルスDNAと適合するものがいないか監視している。（参考：PDBｊ）
Cas9: Cascade 9 (もしくはCRISPR associated protein 9)(参考： Roy et al., 2018 Front Genet.）2018 Cas9は、II型CRISPR系に分類される。監視タンパク質と切断を実行する部分の両方が1本のタンパク質鎖の中に収められている。（参考：PDBｊ） cas9 (formerly named “cas5” or “csn1”) is the signature gene for type II systems (8)（出典：Gasiunas et al., 2012;PNAS 109(39)E2579-E2586）
一般読者向けCRISPR解説記事
CRISPR Part 1: A Brief History of CRISPR (TWIST BIOSCIENCE Dec 12, 2017)
Annotation and Classification of CRISPR-Cas Systems. Kira S. Makarova and Eugene V. Koonin. Methods Mol Biol. 2015; 1311: 47–75. PDF link
Cpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System. BerndZetsche, Jonathan S.Gootenberg, Omar O.Abudayyeh, Ian M.Slaymaker, Kira S.Makarova, PatrickEssletzbichler, Sara E.Volz, JuliaJoung, Johnvan der Oost, AvivRegev, Eugene V.Koonin, Feng Zhang. Cell
Volume 163, Issue 3, 22 October 2015, Pages 759-771. Here, we report characterization of Cpf1, a putative class 2 CRISPR effector. We demonstrate that Cpf1 mediates robust DNA interference with features distinct from Cas9. Cpf1 is a single RNA-guided endonuclease lacking tracrRNA, and it utilizes a T-rich protospacer-adjacent motif. Moreover, Cpf1 cleaves DNA via a staggered DNA double-stranded break.
Expanding the catalog of cas genes with metagenomes. Quan Zhang, Thomas G. Doak, and Yuzhen Ye. Nucleic Acids Res. 2014 Feb; 42(4): 2448–2459.
Evolution and classification of the CRISPR–Cas systems. Makarova et al., 2011. Nature Reviews Microbiology volume 9, pages 467–477（無料Abstract）
CRISPR/Cascade 9-Mediated Genome Editing-Challenges and Opportunities. Bhaskar Roy, Jing Zhao, Chao Yang, Wen Luo, Teng Xiong, Yong Li, Xiaodong Fang, Guanjun Gao, Chabungbam O. Singh, Lise Madsen, Yong Zhou, and Karsten Kristiansen. Front Genet. 2018; 9: 240.
Genome editing: A breakthrough in life science and medicine. Izuho Hatada and Takuro Horii. Endocrine Journal 63(2):105-110. (2016) PDFリンク
総説 ゲノムから見た最近の進化ーCRISPによる生存戦略ー 中川一路 Dental Medicine Research 33(3):236-241. (2013). PDFリンク
原著論文
数が多いため主要な論文のみ挙げています。
CRISPRの発見
Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A. (1987). J Bacteriol 169: 5429-5433. PDFリンク
Unusual Nucleotide Arrangement with Repeated Sequences in the Escherichia coli K-12 Chromosome. ATSUO NAKATA,* MITSUKO AMEMURA, AND KOZO MAKINO. Department of Experimental Chemotherapy, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita, Osaka, Japan 565. Received 19 December 1988/Accepted 13 March 1989 JOURNAL OF BACTERIOLOGY, June 1989, Vol. 171, No. 6 p. 3553-3556 PDF link
Long stretches of short tandem repeats are present in the largest replicons of the Archaea Haloferax mediterranei and Haloferax volcanii and could be involved in replicon partitioning. F.J.M. Mojica C. Ferrer G. Juez F. Rodríguez‐Valera. molecular microbiology July 1995;17(1):85-93
Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. Mojica, F.J.M., Dıez-Villasenor, C., Soria, E., and Juez, G. (2000). Mol. Microbiol. 36, 244–246. PDFリンク
Casの発見
Identification of genes that are associated with DNA repeats in prokaryotes. Jansen R, Embden JD, Gaastra W, Schouls LM. Mol Microbiol. 2002 Mar;43(6):1565-75. PDF link
CRISPRが働くメカニズム と生物学的な意義（細菌に備わる防御機構）
CRISPR provides acquired resistance against viruses in prokaryotes. Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, Romero DA, Horvath P. Science 2007 Mar 23;315(5819):1709-12.
Cas9–crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria.Giedrius Gasiunas, Rodolphe Barrangou, Philippe Horvath, and Virginijus Siksnys. PNASSeptember 25, 2012; 109 (39) E2579-E2586
ゲノム編集技術としてのCRISPR
A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. Science 2012 Aug 17;337(6096):816-21.
Multiplex Genome Engineering Using CRISPR/Cas Systems. Le Cong, F. Ann Ran, David Cox, Shuailiang Lin, Robert Barretto, Naomi Habib, Patrick D. Hsu, Xuebing Wu, Wenyan Jiang, Luciano A. Marraffini, Feng Zhang.Science 15 Feb 2013; Vol. 339, Issue 6121, pp. 819-823
CRISPRに関する最近の論文
C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector.
Omar O. Abudayyeh, Jonathan S. Gootenberg, Silvana Konermann, Julia Joung, Ian M. Slaymaker, David B.T. Cox, Sergey Shmakov, Kira S. Makarova, Ekaterina Semenova, Leonid Minakhin, Konstantin Severinov, Aviv Regev, Eric S. Lander, Eugene V. Koonin, Feng Zhang. Science 02 Jun 2016.
Direct CRISPR spacer acquisition from RNA by a natural reverse transcriptase–Cas1 fusion protein. Sukrit Silas, Georg Mohr, David J. Sidote, Laura M. Markham, Antonio Sanchez-Amat, Devaki Bhaya, Alan M. Lambowitz, Andrew Z. Fire. Science 26 Feb 2016;Vol. 351, Issue 6276
その他のCRISPR-CASに関する論文
Protospacer adjacent motif (PAM)-distal sequences engage CRISPR Cas9 DNA target cleavage.
Cencic R, Miura H, Malina A, Robert F, Ethier S, Schmeing TM, Dostie J, Pelletier J. PLoS One. 2014 Oct 2;9(10):e109213.
参考
Genome damage from CRISPR/Cas9 gene editing higher than thought July 16, 2018, phys.org
Who Will Win the #ChemNobel? Predicting the 2018 Nobel Laureate(s) in Chemistry (American Chemical Society September 27, 2018 @ 2:00pm ET) Feed your frenzy as we once again host our annual predictions webinar that will tide you over until October 3. Join the editors at Chemical & Engineering News and a panel of special guests as they make their best guesses at who will claim chemistry’s big prize during an interactive free broadcast on September 27. Cast your own virtual vote and ask the panelists and hosts questions during a lively discussion of Nobel-worthy science.
世界的な科学情報企業であるクラリベイト・アナリティクス（本社：米国フィラデルフィア、日本オフィス：東京都港区、以下「クラリベイト」）は、2018年の「クラリベイト・アナリティクス引用栄誉賞」を発表致しました。 本賞は、学術論文の引用データ分析から、ノーベル賞クラスと目される研究者を選出し、その卓越した研究業績を讃える目的で発表されています。2002年より毎年9月の発表が恒例化されており、17回目となる本年は、日本人研究者1名を含む17名が受賞しました。日本からは、医学・生理学分野において1名が選出されました。京都大学化学研究所 特任教授 金久實氏は、「KEGG(Kyoto Encyclopedia of Genes and Genomes）の開発を含むバイオインフォマティクスへの貢献 」において今回の受賞となりました。
医学・生理学 Napoleone Ferrara（米国） University of California, San Diego Minoru Kanehisa (日本) Kyoto University, Kyoto, Japan Solomon H. Snyder（米国） Johns Hopkins University, Baltimore, MD
物理学 David Awschalom（米国） University of Chicago, IL Arthur C. Gossard (米国) University of California, Santa Barbara Sandra M. Faber （米国） University of California, Santa Cruz Yury Gogotsi (米国) Drexel University, Philadelphia, PA Rodney S. Ruoff ( 韓国) IBS CMCM Center and Ulsan National Institute of Science and Technology, South Korea Patrice Simon (フランス) Université Paul Sabatier, Toulouse, France
化学 Eric N. Jacobsen （米国） Harvard University, Cambridge, MA George M. Sheldrick (ドイツ) Georg-August-Universitat Gottingen JoAnne Stubbe （米国） MIT, Cambridge, MA
経済学 Manuel Arellano （スペイン） CEMFI, Madrid, Spain Stephen R. Bond （英国） Oxford University, UK Wesley M. Cohen （米国） Duke University, Durham, NC Daniel A. Levinthal（米国） University of Pennsylvania, Philadelphia David M. Kreps（米国） Stanford University, Stanford, CA
2018 KAVLI PRIZE IN NANOSCIENCE
The Norwegian Academy of Science and Letters has decided to award the Kavli Prize in Nanoscience for 2018 to Emmanuelle Charpentier（Max Planck Institute for Infection Biology, Berlin, GERMANY） Jennifer A. Doudna（University of California, Berkeley, USA） Virginijus Šikšnys（Vilnius University, Vilnius, LITHUANIA）
“for the invention of CRISPR-Cas9, a precise nanotool for editing DNA, causing a revolution in biology, agriculture, and medicine.”
2018年ノーベル生理学・医学賞を予想する③ 適応免疫に必須なリンパ球と器官の発見 (毛利 亮子 2018/09/26 15:00:00 Miraikan) オーストラリアの免疫学者、ジャック・ミラー（Jacques F. A. P. Miller）博士, アメリカ合衆国の免疫学者、マックス・クーパー（Max D. Cooper）博士
With prestigious prize, an overshadowed CRISPR researcher wins the spotlight (By Jon Cohen Jun. 4, 2018, 12:45 PM Science) Šikšnys first showed that the CRISPR-Cas9 system, a bacterial immune mechanism, could be transferred from one bacterium to another. He also independently made the same advance as Doudna and Charpentier: developing a way to steer the CRISPR-Cas9 complex to specific targets on a genome, which he called “directed DNA surgery.” … Doudna and Charpentier reported their findings in a landmark Science paper published online on 28 June 2012. But it took Šikšnys 5 months to publish his study; it was rejected by Cell and Cell Reports, and then moved slowly through editing at the Proceedings of the National Academy of Sciences (PNAS), which published it online on 25 September 2012.
When will CRISPR get a Nobel Prize? (PLOS Synbio Community Posted October 5, 2017 by Aaron Dy) Who gets a Nobel for CRISPR? I’ve already referenced the main players, but here’s a very-much-non-definitive list of people rumored to be up for a CRISPR Nobel (in alphabetical order): Emmanuelle Charpentier at Max Planck Institute for Infection Biology in Berlin (fomerly Umeå University), George Church at Harvard University and Wyss Institute, Jennifer Doudna at University of California, Berkeley, Virginijus Šikšnys at Institute of Biotechnology in Lithuania, and Feng Zhang at Broad Institute and MIT.
Why didn’t the discoverers of CRISPR, Jennifer Doudna and Emmanuelle Charpentier, win the Nobel Prize in Medicine? (Quora.com) It was a Dutch group, led by Ruud Jensen, in 2002 that first shed major light on what CRISPR actually is and does. They in fact were the ones who named CRISPR itself as well as the Cas and Cas-associated gene products, and once they had demonstrated that Cas was a selective endonuclease, its potential for recombinant application was quickly appreciated. And it was Yoshizumi Ishino’s group in Japan in the 1980’s that actually “discovered” CRISPRs in the sense of isolating them and their unusual character- palindromic repeats coupled with highly distinctive sequences. (Don Reston, former Biotechnology Specialist (Food and Soil Sciences) Answered Apr 7, 2017)
Nobel Laureate Yamanaka Names Three Japanese Candidates (By Staff Reporter October 6, 2016 at 8:48 am ZAIKEI NEWS) The first research mentioned by Prof. Yamanaka is on PD-1, research that is said to lead to the development of a new drug against cancer. Behind this research is a Kyoto University professor emeritus Tasuku Honjo. … Prof. Yamanaka then mentioned Prof. Yoshizumi Ishino of Kyushu University and Prof. emeritus Atsu Nakada to Osaka university on researches on Genome editing – a technology that could change the entire feature of life. He also quoted a dramatic cholesterol-reducing medication Statin and its discoverer Prof. Akira Endo of Tokyo Univ. of Agriculture and Technology. (Nathan Shiga)
2016年10月5日に、2016年度のノーベル化学賞受賞者が発表されました。受賞したのは分子マシンを設計・合成したジャン＝ピエール・ソヴァージュ(Jean-Pierre Sauvage)氏、ジェームス・フレーザー・ストッダート(Sir J. Fraser Stoddart)氏、バーナード・フェリンガ(Bernard L. Feringa)氏の3人です。
1999年にはフェリンガ氏が分子モーターを合成しました。また、分子で「自動車」も作製しています。下の動画は、Supplementary information from the paper “Electrically driven directional motion of a four-wheeled molecule on a metal surface,” authored by Tibor Kudernac, Nopporn Ruangsupapichat, Manfred Parschau, Beatriz Maciá, Nathalie Katsonis, Syuzanna R. Harutyunyan, Karl-Heinz Ernst & Ben L. Feringa, published in Nature 479: 208–211, 10 November 2011. http://dx.doi.org/10.1038/nature10587
ナノカー2号発進！（今週の分子 Molecule of the Week (58) 有機化学美術館）：”ナノプシャン、ナノカーなど興味深いナノテク世界を切り開いているTour教授の研究室から、また新作が発表されました。今回のニューモデルは、なんと光のエネルギーを受けて自走する「モーター付きナノカー」です。今回組み込まれたモーターは、オランダのFeringaらによって開発されたもので、回転軸となるのは中心にある二重結合部分です。以前述べた通り二重結合はふつう回転できないのですが、光を当てると結合の１本が切れ、自由に回転できるようになります。普通の分子ではどちら向きにでも回ることができ、回転方向を制御することができませんが、Feringaの設計したこの分子ではメチル基の引っかかりにより一方向にのみにしか回転できないようになっています（実際の理屈はもう少し複雑ですが、興味のある方はNature 437, 1337 (2005)あたりをご覧下さい）。”
