The Role of Science Education in the Construction of a Knowledge-Based Society

知識基盤社会における理科の役割は，科学的に探究する活動を通して得られた結果（情報）を活用し，それらの情報から導き出した自らの考えを表現する能力を高めることである。これまでに明らかになったことは，授業者が実験結果に対して関連付けることができる事項を明確にし，分析・解釈する視点を与えることが重要であるということである。今年度は，小学校，中学校，高等学校の理科で，パフォーマンス課題を取り入れた探究活動を行い，多くの授業者が共有できる方向性を考えた。実践の結果，以下のことが明らかになった。１）小集団での話し合いの質を高めるためには，話し合いの目的と方法を明示することが重要であること。２）そのために授業者の関わり方を引き続き検討する必要があること。３）パフォーマンス課題の設計には授業者がよりメタ認知を働かせることが必要であること。今後は，このような実践経験を広く共有すべきであると考えている。Science education should help students to utilize results and information through activities, to investigate scientifically, and to develop their abilities to express ideas they have derived from those results. We have learned that it is important for instructors to clarify which results from experiments relate to each other and to give students some clear perspectives for analyzing and interpreting them. This academic year, we investigated performance tasks at elementary, junior high, and senior high school levels. Through our research we have learned that to improve the quality of discussion in small groups, it is important to make the purpose and method clear. We also showed that instructors should monitor how they engage with students in the course of discussion and that they need to function meta-cognitive abilities more to design performance tasks

Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure.

Tubulin undergoes posttranslational modifications proposed to specify microtubule subpopulations for particular functions. Most of these modifications occur on the C-termini of tubulin and may directly affect the binding of microtubule-associated proteins (MAPs) or motors. Acetylation of Lys-40 on α-tubulin is unique in that it is located on the luminal surface of microtubules, away from the interaction sites of most MAPs and motors. We investigate whether acetylation alters the architecture of microtubules or the conformation of tubulin, using cryo-electron microscopy (cryo-EM). No significant changes are observed based on protofilament distributions or microtubule helical lattice parameters. Furthermore, no clear differences in tubulin structure are detected between cryo-EM reconstructions of maximally deacetylated or acetylated microtubules. Our results indicate that the effect of acetylation must be highly localized and affect interaction with proteins that bind directly to the lumen of the microtubule. We also investigate the interaction of the tubulin acetyltransferase, αTAT1, with microtubules and find that αTAT1 is able to interact with the outside of the microtubule, at least partly through the tubulin C-termini. Binding to the outside surface of the microtubule could facilitate access of αTAT1 to its luminal site of action if microtubules undergo lateral opening between protofilaments

αTAT1 catalyses microtubule acetylation at clathrin-coated pits.

In most eukaryotic cells microtubules undergo post-translational modifications such as acetylation of α-tubulin on lysine 40, a widespread modification restricted to a subset of microtubules that turns over slowly. This subset of stable microtubules accumulates in cell protrusions and regulates cell polarization, migration and invasion. However, mechanisms restricting acetylation to these microtubules are unknown. Here we report that clathrin-coated pits (CCPs) control microtubule acetylation through a direct interaction of the α-tubulin acetyltransferase αTAT1 (refs 8, 9) with the clathrin adaptor AP2. We observe that about one-third of growing microtubule ends contact and pause at CCPs and that loss of CCPs decreases lysine 40 acetylation levels. We show that αTAT1 localizes to CCPs through a direct interaction with AP2 that is required for microtubule acetylation. In migrating cells, the polarized orientation of acetylated microtubules correlates with CCP accumulation at the leading edge, and interaction of αTAT1 with AP2 is required for directional migration. We conclude that microtubules contacting CCPs become acetylated by αTAT1. In migrating cells, this mechanism ensures the acetylation of microtubules oriented towards the leading edge, thus promoting directional cell locomotion and chemotaxis

Molecular basis for diversification of yeast prion strain conformation

Self-propagating β-sheet–rich fibrillar protein aggregates, amyloidfibers, are often associated with cellular dysfunction and disease.Distinct amyloid conformations dictate different physiological consequences,such as cellular toxicity. However, the origin of the diversityof amyloid conformation remains unknown. Here, we suggest thataltered conformational equilibrium in natively disordered monomericproteins leads to the adaptation of alternate amyloid conformationsthat have different phenotypic effects. We performed acomprehensive high-resolution structural analysis of Sup35NM, anN-terminal fragment of the Sup35 yeast prion protein, and foundthat monomeric Sup35NM harbored latent local compact structuresdespite its overall disordered conformation. When the hidden localmicrostructures were relaxed by genetic mutations or solvent conditions,Sup35NM adopted a strikingly different amyloid conformation,which redirected chaperone-mediated fiber fragmentation and modulatedprion strain phenotypes. Thus, dynamic conformational fluctuationsin natively disordered monomeric proteins represent aposttranslational mechanism for diversification of aggregate structuresand cellular phenotypes

A practical approach to motivate the students to study science

本研究では,児童生徒が「理科における学びの愉しさ」を実感するために,さまざまな授業方略を取り入れた授業開発および授業実践を行った。小学校の実践では,「ものの重さ」を取り上げ,誤反応を起こしやすい概念を含んだ課題を意図的に提示することで,児童自身が間違った理解をしていることに気づかせ,修正する授業展開を試みた。中学校の実践では,都市の夕立の学習を通して,都市気候と人間生活との関わりを考察させる授業を行った。生徒は,協同的な学びを通して,ゲリラ豪雨のような異常気象は,人間の生活環境の変化に深い関わりがあることを認識することができた。高等学校の実践では,多酸塩基の緩衝作用の原理について考えさせた。中和滴定の進行に伴って緩衝作用がみられる部分について,その原理を粒子モデルや反応式を使って説明する探究活動を行った。 いずれの授業実践も,実験結果の予想や分析,表現,身近な現象と人間生活との関わりなどについて,児童生徒自らが問いを内発し,疑問を認識し,現象を科学的に説明することを要求する取り組みを行うことで,理科を学ぶことの有用性や意義を実感でき,「学びの愉しさ」を得ることができた

αTAT1 catalyses microtubule acetylation at clathrin-coated pits.

In most eukaryotic cells microtubules undergo post-translational modifications such as acetylation of α-tubulin on lysine 40, a widespread modification restricted to a subset of microtubules that turns over slowly. This subset of stable microtubules accumulates in cell protrusions and regulates cell polarization, migration and invasion. However, mechanisms restricting acetylation to these microtubules are unknown. Here we report that clathrin-coated pits (CCPs) control microtubule acetylation through a direct interaction of the α-tubulin acetyltransferase αTAT1 (refs 8, 9) with the clathrin adaptor AP2. We observe that about one-third of growing microtubule ends contact and pause at CCPs and that loss of CCPs decreases lysine 40 acetylation levels. We show that αTAT1 localizes to CCPs through a direct interaction with AP2 that is required for microtubule acetylation. In migrating cells, the polarized orientation of acetylated microtubules correlates with CCP accumulation at the leading edge, and interaction of αTAT1 with AP2 is required for directional migration. We conclude that microtubules contacting CCPs become acetylated by αTAT1. In migrating cells, this mechanism ensures the acetylation of microtubules oriented towards the leading edge, thus promoting directional cell locomotion and chemotaxis

The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.

Centrioles are microtubule-based, barrel-shaped structures that initiate the assembly of centrosomes and cilia. How centriole length is precisely set remains elusive. The microcephaly protein CPAP (also known as MCPH6) promotes procentriole growth, whereas the oral-facial-digital (OFD) syndrome protein OFD1 represses centriole elongation. Here we uncover a new subtype of OFD with severe microcephaly and cerebral malformations and identify distinct mutations in two affected families in the evolutionarily conserved C2CD3 gene. Concordant with the clinical overlap, C2CD3 colocalizes with OFD1 at the distal end of centrioles, and C2CD3 physically associates with OFD1. However, whereas OFD1 deletion leads to centriole hyperelongation, loss of C2CD3 results in short centrioles without subdistal and distal appendages. Because C2CD3 overexpression triggers centriole hyperelongation and OFD1 antagonizes this activity, we propose that C2CD3 directly promotes centriole elongation and that OFD1 acts as a negative regulator of C2CD3. Our results identify regulation of centriole length as an emerging pathogenic mechanism in ciliopathies

Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure

Tubulin undergoes posttranslational modifications proposed to specify microtubule subpopulations for particular functions. Most of these modifications occur on the C-termini of tubulin and may directly affect the binding of microtubule-associated proteins (MAPs) or motors. Acetylation of Lys-40 on α-tubulin is unique in that it is located on the luminal surface of microtubules, away from the interaction sites of most MAPs and motors. We investigate whether acetylation alters the architecture of microtubules or the conformation of tubulin, using cryo–electron microscopy (cryo-EM). No significant changes are observed based on protofilament distributions or microtubule helical lattice parameters. Furthermore, no clear differences in tubulin structure are detected between cryo-EM reconstructions of maximally deacetylated or acetylated microtubules. Our results indicate that the effect of acetylation must be highly localized and affect interaction with proteins that bind directly to the lumen of the microtubule. We also investigate the interaction of the tubulin acetyltransferase, αTAT1, with microtubules and find that αTAT1 is able to interact with the outside of the microtubule, at least partly through the tubulin C-termini. Binding to the outside surface of the microtubule could facilitate access of αTAT1 to its luminal site of action if microtubules undergo lateral opening between protofilaments