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燈號說明

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翻譯：劉育男(簡介並寄信)
編輯：邱富敏(簡介並寄信)
研究報告與口頭報告指導方針
Paper and Oral Presentation Guidelines

關於蛋白質摺疊、錯誤摺疊以及它們的生理意義的研究報告是本課程重點之一
The Research Reports are an essential part of the course curriculum, and cover important topics in protein folding, misfolding, and their physiological roles.

口頭報告
Oral Presentation

報告時間為20分鐘，各組中每一成員10分鐘。之後有五分鐘的發問與討論
The oral presentations will be 20 minutes each with each team member giving 10 minutes. A five minute question and discussion period will follow.

一篇10-15頁的文章約需要30-45分鐘來闡述。 所以臨場報告須根據書面報告內容整理過，理出關鍵問題、重要實驗、流程、結果與解讀。
A 10-15 page paper requires 30-45 minutes for oral presentation. Therefore the live class presentation, though following your manuscript content, needs to be specifically constructed and tuned as an oral presentation. In particular you need to pull out a key question, critical experiment, its protocol, results, and interpretation.

假設你參加一個科學研討會，試用下列格式來呈現你的重點：
Assume you are at a scientific meeting; use overheads to illustrate key points where convenient. Try to follow the format of:

  • 先列出問題
    first posing the question;
  • 然後描述用來解答上述問題的實驗設計
    then describing the experiments designed to answer the question;
  • 報告實驗結果
    report the result;
  • 最後，分析並解讀實驗結果
    finally analyze and interpret the results.

如同作一個專業的報告，報告前應該盡量先預講練習並請同學計時
As in a professional presentation, the presentations should, if possible, be rehearsed and timed beforehand to another member of the class.

時程
Timing

口頭報告前你應該先閱讀吸收並分析你所讀的資料。除了最後一天報告的那組，無論何時報告，書面報告都應該在最後一節(第24節)繳交；而最後一組有多兩天的寬限期。報告當天應該發給同學摘要。
In order to present to the class, much of your reading, assimilation, and integration needs to be done before the day of presentation. However, the actual final written papers are due on the last day of class, session 24, regardless of when you presented. The exception is for the groups presenting on the last day of class, who will have two more days, to hand in written papers. You will need to have the abstracts available for the class on the day you are presenting.

學生口頭報告從第19節到第25節
Student presentations will start from session 19 onwards and continue through session 25.

書面報告方針
Paper Guidelines

期末報告的格式應該是所選主題的小回顧。在你完成報告之時你應該是該主題的專家，應該儘可能地讓你的同學了解你所學。
The format of the final papers should be a Minireview of the selected topic. At the point you have completed the paper you should be an expert on the subject, with the additional good feeling of having made your understanding available to your classmates.

報告內容應該先有一個簡介介紹這門學問的背景，然後舉出重要的結果與討論來回顧你認為重要的發現。試用下列格式: 先列出問題；然後描述設計來解答問題的實驗；分析並解讀實驗結果。選用一些圖來解說主題。
The text should begin with an introduction which gives the background and general context of the work. This is to be followed by a Critical Results and Discussion section which reviews the findings that you consider most relevant and important. Try to follow the format of first posing the question; then describing the experiment designed to answer the question; finally analyzing the resulting data. Reproduce a few figures to illustrate aspects of the subject.

書面報告應包含一個有250字以內的重要結果與結論總結的首頁。總結後面要附上一篇回顧、一篇新近的研究與一篇你認為重要的報導做為參考文獻。報告當天應該發給同學一份摘要。
The paper should consist of a title page with a summary (<250 words) of the most important results and conclusions. At the end of the summary give the reference to a review article, a very recent research paper, and a paper you consider to be seminal. The abstracts will be copied and distributed to the class.

書面報告為10-15頁不超過十五頁的兩倍行距格式的報告，參考文獻與圖另計
The length of the text proper should be 10-15 double spaced pages, with 15 pages the absolute limit. The references and figures are additional.

參考文獻須附上其標題。
The references should include the titles of the papers.

其他同學即是你的聽眾。
The target audience is the other students in the class.

學員口頭報告的主題
Student Presentation Topics

專題 課程單元 描述
十一月的報告：蛋白質試管內摺疊/蛋白質結構與序列
November Presentations: Protein Folding in vitro / Protein Structure and Sequences
1 芳香環支鏈在球蛋白內的構型
The Conformations of Aromatic Side Chains in Globular Proteins		 大部分的芳香環被發現於蛋白質內部。請問芳香環在蛋白質內部參予何種作用？有證據指出芳香環在蛋白質內部可以彈跳。這種彈跳有多快？有多普遍？
Most aromatic rings are found in the interior of proteins. What kinds of interactions are aromatic rings involved in within protein interiors? There is evidence in some proteins that the rings can flip. How rapidly? How general is this motion?
2 試管內膠原蛋白的再摺疊
The in vitro Refolding of Collagen		 類膠原蛋白序列的胜肽鏈結構最近剛被核磁共振與x射線繞射光譜所解出。 利用二維核磁共振光譜可以監測胜肽鏈摺疊與結合反應的實際動力學狀態以及置換某些甘胺酸的影響。
Short tripeptides with collagen-like sequences have recently been crystallized and their structure solved by X-ray diffraction. Using 2-D NMR it has been possible to follow the actual kinetics of the chain folding and association reaction and the effects of certain glycine substitutions.
3 雙股、三股、四股的捲曲環圈
Two Stranded, Three Stranded, Four Stranded Coiled Coils		 捲曲環圈並不侷限於一對，而是受包埋在內的疏水性胺基酸所影響，螺旋股可以形成三體或更高的聚合體。 近期研究更指出序列與三級結構的關係。
Coiled coils are not limited to pairs; depending on the details of the residues at the buried hydrophobic positions, the helices will form trimeric and higher associations. Recent studies reveal the fine points of the relationship between sequence and tertieary associations.
4 靜電交互作用在捲區環圈的摺疊，結合，與生成
Electrostatic Interations in the Folding, Association and Registration of the Coiled Coils		 雖然胜肽鏈間疏水性交互作用很重要，然而帶電荷的交互作用也控制如肌凝蛋白及白胺酸拉鍊的結構與捲曲環圈的聚合。近期的報導指出各個這類離子對在結構穩定性的貢獻。
Though the hydrophobic interactions are critical, charged side chains interactions also control the structure and association of coiled/coils in both tropomyosin, and leucine zippers. Recent papers report differing values for the contributions of these ion pairs to stability.
5 Beta迴轉是否形成可溶解胜肽？
Do Beta Turns Form in Soluble Peptides?		 近期對合成胜肽鏈的核磁共振研究指出，beta迴轉可能比想像中更穩定，其可能是形成蛋白質摺疊的核心的人選。
Recent NMR studies of synthetic peptides suggest that beta turns may be more stable than expected and might be candidates for protein folding nuclei.
6 在球蛋白內的螺旋延伸與終止訊號
Helical Extension and Termination Signals in Globular Proteins		 從序列的分析指出螺旋區的末端有其偏好的殘基。在芽孢桿菌核酸酶與T4噬菌體溶菌酶中取代末端殘基則會改變螺旋末端的生成。
Analysis of sequences at the ends of helical regions reveal preferred residues. In both Barnase and T4 lysozyme substitutions have been generated which alter the termini of helices in the proteins.
中段主題 - 十一月後期
Mid Session Topics - Late November
7 原肌紅素的再摺疊途徑
The Refolding Pathway For Apomyoglobin		 氫原子交換與核磁共振被廣泛地應用來鑑定原肌紅素再摺疊的中間產物；這些研究有助於解讀各種人類血紅素突變株與序列資料。
Hydrogen exchange and NMR have been used to identify intermediates in the refolding of apomyoglobin. This allows interpretation of a variety of human hemoglobin mutants and other sequence data.
8 環狀交換的多胜肽鏈
Circularly Permuted Polypeptide Chains		 胺基酸序列的連續性與連接性有多重要呢?在牛胰蛋白脢抑制蛋白(BPTI)這個希臘鑰匙型的beta 圓筒蛋白及其他較大的酵素，胺端跟羧端被連接起來並產生新的末端，來研究序列交換對折疊的影響。
How important is the continuity and connectedness of amino acid sequences? In BPTI, the Greek key beta barrel proteins and some larger enzymes, the N- and C- termini have been joined together and new physical ends created, to examine the effects of sequence permutation on chain folding.
9 T4噬菌體溶菌酶的突變研究
Mutational Studies with T4 Lysozyme		 在各種已知原子級解析度的蛋白質中，T4噬菌體溶菌酶其胺基酸序列突變對其分子構型和摺疊穩定度的影響是被研究得最透徹的。 這些實驗提供了局部序列與整體的摺疊的關係也帶來一些有用的驚喜。
Among proteins of known atomic structure, extensive studies of the affects of mutations on the conformation and stability of the folded protein have been carried out with T4 lysozyme. These experiments have yielded both insight into the relationship of local sequence and overall fold, and some useful surprises.
10 Beta平板蛋白的摺疊
Folding of Beta Sheet Proteins		 近期的研究已開始鑑定出如介白素或是脂肪酸結合蛋白等beta平板蛋白的生成的中間產物。 這些實驗使用了氫/氘交換配合光譜技術。
Recent studies have begun to identify intermediates in the formation of small beta sheet proteins such as the interleukins and fatty acid binding proteins. These experiments utilize both hygrogen/deuterium exhange combined with spectroscopic procedures.
11 螢光素的摺疊伴隨著次單位交互作用
Coupling of Folding and Subunit Interaction in Luciferase		 許多寡體蛋白組合時並非由自然態次單位形成而是由次單位摺疊中間產物形成的。 其中照亮深海魚類眼睛的細菌螢光素其異雙體結構即是大家所熟知的例子。
In many oligomeric proteins assembly proceeds not from native subunits but from folding intermediates of the subunits. One of the best understood cases is the heterdimeric luciferase from the bacteria that illuminate the eyes of deep sea fish.
12 菌視紫紅質的摺疊與插入
Folding and Insertion of Bacteriorhodopsin		 視覺器官的視紫質蛋白是少數三維結構被解出來的膜蛋白之一。 幾個精良設計的實驗即是利用了細菌和哺乳類視蛋白來研究穿膜螺旋如何與細胞膜結合。
One of the very few membrane proteins whose three dimensional structure has been solved is the rhodopsin of the visual system. The best defined experiments on how these transmembrane helices associate within the membrane have been done with the bacterial and mammalin opsin.
十二月的報告：細胞胞器之於蛋白質摺疊
December Presentations: Cellular Apparatus for Protein Folding
13 核醣體上新生鏈的構型
The Conformations of Nascent Chains on the Ribosome		 剛合成的多胜肽鏈在核醣體上是什麼構型？核醣體是否參與蛋白質的早期摺疊？激發因子的角色為何？
What is the conformation of the newly synthesized polypeptide chain as it exits the ribosome? Does the ribosome play a role in early stages of protein folding? What are the roles of Trigger Factor?
14 脯氨酸基羥化酶在膠原蛋白的鏈折疊與熟成的功用
Functions of Prolyl Hydroxylases in Collagen Chain Folding and Maturation		 脯氨酸基羥化酶負責在新合成的鏈上產生羥化脯氨酸並被認為參與調節三絞螺旋的生成。 低度脯胺酸羥化是維生素C缺乏的壞血病的分子層級缺陷。
Prolyl hydroxylase is responsible for the formation of hydroxyproline on newly synthesized chains and is thought to be involved in regulating triple helix formation. Underhydroxylation of prolines is the molecular defect in scurvy, vitamin C deficiency.
15 脯胺酸異構酶在蛋白質摺疊的角色
The Role of Prolyl Isomerase in Protein Folding		 脯胺酸異構化的功能為何?脯胺酸異構酶在細胞內對新合成的多胜肽鏈(包括前膠原蛋白)的摺疊有何影響?脯胺酸異構酶原本稱為親和素，是環孢子素這類免疫抑制藥劑的目標。
What is the role of proline isomerization and proline isomerase in the folding of newly synthesized polypeptide chains within cells, including pro collagen? Prolyl isomerase, originally called cyclophilin is the target of the cyclosporin class of immunosuppressive drugs.
16 菌孔道蛋白的摺疊與組合
Folding and Assembly of Bacterial Porins		 菌孔道蛋白是一類膜蛋白，其膜蛋白孔道是由數個大型的beta圓筒而非alpha螺旋所組成，它的三維結構已被解出。
The porins are a class of membrane proteins making large pores which use large beta barrels rather than alpha helical proteins and whose 3-D structures have been solved.
17 參與原核生物雙硫鍵生成的蛋白
Prokaryotic Proteins Involved in Disulfide Bond Formation		 遺傳學研究鑑定出一族在細菌中參與硫醇氧化與還原的蛋白，並且認為這些蛋白影響某些蛋白的摺疊。
Genetic studies in bacteria have identified a family of proteins involved in reduction and oxidation of thiols, and presumed to be involved in the folding of some proteins.
18 雙硫鍵異構酶在內質網所扮演的腳色
The Role of Protein Disulfide Isomerase in the Endoplasmic Reticulum		 在真核細胞新合成的多胜肽鏈如何產生雙硫鍵並且被送到胞外?
How are disulfide bonds formed in newly synthesized polypeptide chains destined for export from eukaryotic cells?
19 流感病毒紅血球凝集素的胞內折疊與組合
In vivo Folding and Assembly of the Influenza Hemagglutinin		 這個三體病毒外鞘蛋白的胞內組合是一個不錯的真核蛋白摺疊模型。
The intracellular assembly and maturation of this trimeric viral coat protein is one of the better model systems in eukaryotic cells.
20 SecB伴隨蛋白在蛋白輸出的分派
The secB Chaperonins in Proteins Destined for Export		 一些要被分派到胞外(或是在胞外摺疊)的蛋白在合成後必須先保持未折疊，secB是大腸桿菌中用來維持這個狀態的蛋白中被研究相當透徹的蛋白。
A number of proteins destined for export (and perhaps folding) outside the cell must be maintained in a non-folded state after synthesis. Some of those are maintained in this state by the secB protein of E.coli, whose mechanism has been studied in considerable detail.
21 GroE S伴隨蛋白的功能與結構
Structure and Functions of the Eukaryotic Dedicated GroE S Chaperonins		 GroE為一種保留的十四次單位寡體，至少在高溫時參與確保新生蛋白鏈的正確摺疊。
A conserved class of 14 subunit oligomers, the GroE chapoeronins, is involved in insuring the correct folding of newly synthesized chains, at least at high temperature.
22 GroE幫助蛋白質摺疊的機制
The Mechanism of GroE Function in Protein Folding and Asssembly		 伴隨蛋白實際上如何幫助蛋白摺疊，這個玩偶匣是怎麼作用的？ATP水解如何驅動伴隨蛋白作用？
How does the chaperone actually function in ensuring productive protein folding? How does the Jack in the Box work, how is ATP hydrolysis coupled to chaperone function?
23 伴隨蛋白在細菌纖毛組合過程中的作用
Chaperonin Function in Bacterial Pilus Assembly		 細菌用纖毛與鞭毛來游泳、附著至另一細胞及運送遺傳物質DNA。 形成這種胞器的蛋白要折疊或組合需要一類作用於膜間腔的特殊的伴隨蛋白。
Bacteria use extra cellular flagelli and pili for swimming, attaching to other cells and transporting DNA. The folding and assembly of the proteins for these organelles utilize specialized chaperonins some of which function in the bacterial periplasm.
24 蛋白質輸出輸入的通道
Channels for Protein Import and Export		 許多新合成的蛋白必須通過膜層，例如送入粒腺體或內質網的蛋白。一般而言，多胜肽鏈必須先保持未折疊。 在一些生物體中形成這類通道的蛋白已被鑑定出來。
Many newly synthesized proteins have to transit a membrane, for example, for import into mitochondria or for entry to the endoplasmic reticulum. In general, the polypeptide chains have to be maintained in an unfolded state. The proteins forming these channels have recently been identified in a number of organisms.
25 DNA K (HSP90)類型伴隨蛋白的功用
Function of the DNA K (HSP90) Class of Chaperonins		 這類蛋白似乎作用在GroE之前的胜肽鏈合成階段，通常以DNA K、 DNA J以及Grp E.複合體的型態作用。
These appear to interact with newly synthesized chains at an earlier stage in folding than the GroE class, and function as a complex of DNA K, DNA J, and Grp E.
後期的報告：蛋白質摺疊錯誤與疾病
Later Presentations: Protein Misfolding and Disease
26 水晶體晶狀蛋白與白內障
Lens Crystallins and Cataracts		 水晶體的蛋白"晶狀蛋白"有許多不尋常的特色，至少它是高濃度存在。Gamma晶狀蛋白可在試管內再摺疊且其三維立體結構已經被解出。 一些研究者相信這些分子的不正確結合會導致白內障。
The proteins of the lens, crystallins, have a variety of unusual properties, at least at high concentrations. The three-dimensional fold of the Gamma crystallin has been solved and the protein can be refolded in vitro. Some investigators believe incorrect association of these molecules leads to cataracts.
27 阿茲海默症的類澱粉體沈積
Amyloid Deposits in Alzheimers Disease

阿茲海默症的病患的許多組織內有著不可溶的蛋白沈積，一個主要的類型的特色為具有特殊的交叉的beta圓柱結構。
Alzheimers patients have insoluble protein deposits in a number of their tissues. A major class are characterized by a distinctive cross beta rod structure.

  • 主題 A: 阿茲海默胜肽的試管內聚合的研究
    Topic A: Studies on the in vitro association of the Alzheimer's peptide.
  • 主題 B: 類澱粉斑在活體內的生成
    Topic B: Formation of amyloid plaques in vivo.
28 蛋白感染素疾病其蛋白質結合現象
Prion Diseases as Protein Association Phenomoma

越來越多的證據指出蛋白感染素疾病(如狂牛病)是因為蛋白質結合過程中其構型產生不可逆的改變，可能是由類澱粉體堆積相關的機制造成。
The evidence is accumulating that prion diseases are due to proteins which change their conformation irreversibly during an association reaction, perhaps by mechanisms related to amyloid accumulation.

  • 主題A：鑑定蛋白感染素的病源與它的傳染性
    Topic A: Indefication of the prion agent and its transmissability.
  • 主題B：單離的蛋白感染素的結構研究
    Topic B: Structural characterization of the isolated prion protein.
29 輕鏈澱粉樣病變
Light Chain Amyloidosis		 一種稱為多發性骨髓瘤的血癌癌症病患好發輕鏈生產過量的類澱粉堆積。 這凝集反應的某些部份可以在試管實驗再現。
Cancer patients with a form of leukemia called multiple myeloma often accumulate amyloid deposits composed of the overproduced light chains. Some aspects of this aggregation reaction can be reproduced in vitro.
30 纖維性囊腫的CFTR缺陷
The CFTR Defect in Cystic Fibrosis		 纖維性囊腫的病因是因為呼吸道的氯離子傳送蛋白質有缺陷，近年的證據指出最常見的遺傳形是因為蛋白質摺疊缺陷。
Cystic fibrosis is due to a defect in the chloride transporter protein in the respiratory tract. Recent evidence indicates that the most common inherited form is due to a protein folding defect.
31 肌萎縮性脊髓側索硬化症(漸凍人症)的超氧化物歧化酶缺陷
Superoxide Dismutase Defect in ALS (Lou Gehrig's Disease)		 近年的證據指出肌萎縮性脊髓側索硬化症與超氧化物歧化酶這個廣泛分布的酵素有關，相關的胺基酸取代會影響此酶的摺疊及穩定性而非代謝功能。
Recent evidence indicates that amylotrophic lateral sclerosis is associated with a defect in the function of the widely distributed protein Superoxide Dismutase. The associated amino acid substitution may affect folding or stability rather than metabolic function.
32 家族性肺病的抗胰蛋白酶缺陷
The Anti-Trypsin Defect in Familial Lung Disease		 漸增的肺對菸與灰塵傷害的敏感性被認為與某些作用在肺的抗彈性蛋白的對偶基因有關，近年的證據顯示主要的家族形是因為蛋白質摺疊缺陷。
Increased susceptibility to lung damage from smoking and dusts is associated with certain alleles of the anti-elastase that functions in the lung. Recent evidence reveals that their major familial form is due to a defect in the folding of the protein.
33 trans-thyretin與類澱粉疾病
Trans-thyretin and Amyloid Disease		 一類稀少但被研究透徹的類澱粉疾病是因為trans-thyretin這個視黃醇攜帶蛋白的沉積，試管內的摺疊與展開反應的特色與病理狀況相符。
A rare but well studied slass of amyloid diseases are due to deposition of the carrier protein trans-thyretin which is a retinol carrier protein. Features of the in vitro unfolding/ refolding reaction correlate with the conditions that yield pathology.
34 抑癌蛋白質基因的突變
Mutations in Tumor Suppressor Proteins		 腫瘤的生成通常與一群控制DNA複製或細胞分裂的胞內蛋白的失能有關，有些證據指出p16錨蛋白的某些突變也是造成蛋白摺疊缺陷。
Loss of function of a number of cellular proteins, which control DNA replication and cell division, is associated with tumor formation. There is some evidence for the p16 ankyrin proteins that some of these mutations may represent protein folding defects.
35 蛋白質凝集與杭丁頓症
Protein Aggregation in Huntington's Disease		 與出杭丁頓症有關的多蛋白膠黏產物最近被鑑定出，它的凝集型被發現於細胞核。
The protein polyglutimate product associated with Huntington's disease has recently been identified. An aggregated form of it is found within the cell nucleus.

 
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