Biochemistry and Molecular Biology Teaching

Ming-Derg Lai

http://140.116.60.1/mdlai/Handout/handout.htm

Faculty in the University

教學

傳統教

學 網路教

學小組教

學

○

傳統教學啟發式教

學 填鴨式教

學

啟發式教學？不憤不

啟不悱不

發

論語│

述

而

朱熹《論語集注》的解釋是：

憤者，心求通而未得之意。

悱者，口欲言而未能之貌。

啟，為開其意。發，為達其辭。

Problem-Based Learning摘要某學生之反應：

開始時、並非自己沒有先作功課，雖然查了一堆資料，卻抓不到問題的核心，囫圇吞棗般的消防化不良，更糟的是想發表意見時又辭不答意，沒有條理。

教學時、整個討論結束後老師會為我們的表現作評論，包括我們思考準備的方向，觀念是否正確，是否遺漏什麼重點． ．等等。這樣的引導下，覺得自己漸漸上了軌道，學會拿到題目後，如何分析問題，抓住 keywords找資料，資料的來源也較多元化，除了 textbooks外，網路上的資訊更多更新 ; 有時問題的答案可能不好找，以基本的知識加以推理思考問題的答案，也是訓練的指標之一。

結果、不知從何時開始發現自己對小組有愈來愈多建設性的貢獻。

Comments on Problem-Based Learning

• Academic staff worry that there does not seem to be any clear curriculum and that students might finish up knowing different things.

• But the most important feature of this method is that it accepts that it is impossible for any one person to remember enough of the vast body of knowledge that constitutes modern biochemistry and molecular biology to solve the problems that they might encounter in their work, and also that knowledge has no intrinsic value if it cannot be used (for example, to solve problems).

• Finally, problem-based learning encourages group work and gives students responsibility for their own learning.

• The experience is that this is effective, but takes even more staff time plus initial training of staff to act as facilitators rather than teachers.

傳統教學方式• 中人以上，可以語上也；中人以下，不可以語上也。。─論語─雍也

• 君子引而不發。─孟子• 教也者，長善而救其失也。─學記• 善問之人，如匠善攻治堅木，先研治其濡易之處，然後砍其節目。─禮記正義

教學

設定教學對象

選定教學內容

現場教學方式

學習成果檢驗

教學對象

學生資質

人數

10

20

教學對象

學生資質

人數

10

20

教學對象• Undergraduate or Graduate?

• We must be aware that student background usually get better each year.

• Quality of students may change in different years. (you can judge from the student’ answer to your question in the class.)

教學

設定教學對象 ( 大多數或優秀群 )

選定教學內容

現場教學方式

學習成果檢驗

中人以上，可以語上也；中人以下，不可以語上也。─論語─雍也

教學內容： Overflow of information

• Have we equipped such students with the skills to tackle their rapidly evolving subject?

• Asking this question is worthwhile because, paradoxically, the increasing mass of information that biochemistry students now face might be hindering their future ability to analyze that information.

• Considering the past might help us to shape the future of education in the molecular life sciences

The evolution of textbooks

1950 1960 1970 1980 1990-2000

Linear description

More figuresMath and Chemdowngraded

Two-colorstart logicsof biochem.Stryer: full color, problems.

The firstmolecular cell textbook,DNA comesfirst.

CD-ROMs, problems,instructors texts, study guides, transparenciesweb sites.

The changing faces of textbooks

a | The Meselson and Stahl experiment according to Baldwin, Dynamic Aspects of Biochemistry fourth edition (1963) (C) Cambridge Univ. Press, and b | accordingto Mathews and Van Holde (1996), Biochemistry, second edition, (C) Benjamin Cummings, Redwood City, California.

The future of education in the molecular life sciences

• The changing landscape of education in biochemistry and molecular biology presents many challenges for the future, for students and educators alike.

• The exponential increase in knowledge, the genomics, proteomics and computing revolutions, and the merging of once separate fields in biology, chemistry, physics and mathematics, mean that we need to rethink how we should be preparing today's science students for the future. What do we need to change, and how will we implement it?

Tackling the expansion of knowledge• There is now too much information around for anyone to know and

memorize: the teacher does not know it all and the student certainly cannot be expected to remember it all. As educators, we should ask: what are the qualities that we need future molecular life scientists to have? By identifying these we can then begin to think about how these qualities can be instilled into future undergraduates of biochemistry and molecular biology.

• A related issue is whether or not there is a necessary core of material that a student should be expected to know. Do students really need to know the structure of prostaglandin E2, the formal kinetic mechanism of glutamate dehydrogenase, the specificity of EcoR1 or the roles of the Grim and Reaper proteins in apoptosis, so long as they know how to access this information if they need it?

教學內容之選擇• 選擇適合學生未來工作研究需求之內容 ，而不是過去教師學習時課程之重點。 ( 教師從事研究工作將有助判斷 )

• 教師取得課程內容共識。• 不只傳遞知識，也傳授方法。• 君子引而不發。─孟子

Schonefeld: Training Mathematics Problem Solving

• 如果真的可能， 試畫圖解表 示。• 若有整數參數出現，就尋找歸納式論 證 (inductive argument)。• 以較少的變項，考 慮一個類似的問題。• 嘗試建立次目標。• 考慮用 「矛盾法」 (contradiction) 和 「對換法」 (contra-positive)來做論證。– 對換法 :不直接丟證明 「倘 X 為真， 則 Y 為真 」，你可以去證明

等值語句 「倘Y 為假，則X 必為假」。– 矛盾法 :為了要 做論證，先 把你想要證明的語 句假定為假。使用這

一假定，繼續證明「問題中某一已知條件為假」 ;「你知其為真的某些事物為假」，或者 證明 「你想證明的事 物為真 」。如果 你能夠做到這些之中的 任何一個，則你已證明了你想證明的事 物。

The ideal education in biochemistry

1. Understanding of the fundamentals of chemistry and biology and the key principles of biochemistry and molecular biology.2. Awareness of the major issues at the forefront of the discipline. 3. Ability to assess primary papers critically.4. Good 'quantitative' skills, such as the ability to prepare reagents accurately and reproducibly for experiments.5. Ability to dissect a problem into its key features.6. Ability to design experiments and understand the limitations of what the experimental approach can and cannot tell you.7. Ability to interpret experimental data and identify consistent and inconsistent components.8. Ability to design follow-up experiments.9. Ability to work safely and effectively in a laboratory.10. Awareness of the available resources and how to use them, including the ability to collaborate with other researchers.11. Ability to think in an integrated manner and look at problems from different perspectives.

What do budding biochemists need to understand?

1. Fundamentals of macromolecular structure and function; how to determine macromolecular structure.2. Modes of macromolecule–ligand interactions and approaches to study them.3. Basic concepts of biocatalysis (including ribozymes). 4. Enzyme kinetics and inhibition.5. Basic mechanisms of the control of cellular processes and reactions. 6. Techniques of macromolecular isolation and characterization.7. How to use sequence and structural databases.8. Fundamentals of computational chemistry and molecular modeling.

What do budding biochemists need to understand?

9. The uses of techniques such as cloning, polymerase chain reaction, site-directed mutagenesis, phage display and array technology.10. Cellular structure and compartmentalization including the functions ofsubcellular organelles.11. Basic mechanisms of cell division and macromolecular synthesis. 12. Basics of tissue development and differentiation.13. Basics of genetic disease.14. Fundamental differences between prokaryotes and eukaryotes; molecular evolution.15. Fundamentals of cellular and molecular immunology, and the fundamental lifestyles of pathogens such as bacteria and viruses.

How biochemistry has been taught in the United Kingdom

教學

設定教學對象 ( 大多數或優秀群 )

選定教學內容 ( 學生未來之需求，方法 共識之新課程 )

現場教學方式

學習成果檢驗

教學方法 :Changing Teaching Methods

• Although the traditional lecture still forms the basis of most undergraduate courses, new teaching methods have been devised, including group work (such as designing a poster together and problem-based sessions), reflection on how learning took place, peer marking and peer assessment, as well as the use of computers. Although these help to deal with diminishing staff-to-student ratios, they have other benefits too: for example, collaborative projects teach students how most people work in the 'real world', give students responsibility, and encourage active learning.

傳統教學方式建 議•連續性課程，在上課開始時， 使用1-2分鐘回顧前一堂課內容。

•在上課結束時，使用2-3分鐘複習本堂課內容。

•一分鐘考卷：保留下課最後一分鐘要求學生對一 兩個問題在紙上陳述作答。 這些問題可能是： 今天上課最重要的內容或是他們最聽不懂的部份。這 些問題可提供師生雙向溝通。

•追蹤考核這些討論是 必須的。

準備傳統教學內容之建 議

• 教學投影片或幻燈片是幫助學生了解，而非 供老師閱讀，不應 含太多文字。若有很多內容須放在同一張投影片，則可標示其重點 部分。

• 圖解有 利於學生了解。

APC

1. Adenomatous polyposis coli (APC) tumor suppressor gene binds to -catenin, a protein interacts with Tcf and Lef transcription factors.

2. APC deficient colon cells contain a stable -catenin/TCF complex which constitutively activate the TCF-regulated gene expression (such as myc).

APC

1. Adenomatous polyposis coli (APC) tumor suppressor gene binds to -catenin, a protein interacts with Tcf and Lef transcription factors.2. APC deficient colon cells contain a stable -catenin/TCF complex which constitutively activate the TCF-regulated gene expression (such as myc).

WNT

Cell membrane Nuclear membrane

GSK3 -catenindsh Tcf/Lef myc

APC

JNK null mice• Mice deficient of JNK1 or JNK2 appear to be morphologically normal. However, these mice are

immunodeficient due to severe defects in T cell function. No evidence for a defect in T cell activation (proliferation and IL-2 secretion) was obtained. Instead, the deficiency was identified as a requirement of JNK for the appropriate differentiation of CD4 T helper cells into effector cells. The mechanism was reported to be mediated, in part, by alterations in the function of the NFAT1 transcription factor and by defects in IFN secretion . In contrast, one group has reported that JNK2 may be required for T cell activation at low levels of stimulation and that the mechanism is mediated, in part, by JNK-dependent regulation of IL-2 mRNA stability. Nevertheless, there is agreement amongst all of these reports that at moderate and high levels of immune challenge, JNK is not required for T cell activation. However, JNK is required for effector T cell function. An important question concerns why T cells are sensitive to defects in JNK1 or JNK2 expression. This may result from the pattern of JNK expression in murine T cells. Immature T cells (thymocytes) express high level of JNK1 and JNK2. However, JNK expression is down-regulated in peripheral T cells. JNK is therefore expressed at low levels in naive T cells, but the expression of JNK is up-regulated following immune challenge. The low level of JNK expression in naive T cells may account for the sensitivity of these cells to targeted disruption of the Jnk genes.

JNK null mice• Mice deficient of JNK1 or JNK2 appear to be morphologically normal. However, these mice are

immunodeficient due to severe defects in T cell function. No evidence for a defect in T cell activation (proliferation and IL-2 secretion) was obtained. Instead, the deficiency was identified as a requirement of JNK for the appropriate differentiation of CD4 T helper cells into effector cells. The mechanism was reported to be mediated, in part, by alterations in the function of the NFAT1 transcription factor and by defects in IFN secretion . In contrast, one group has reported that JNK2 may be required for T cell activation at low levels of stimulation and that the mechanism is mediated, in part, by JNK-dependent regulation of IL-2 mRNA stability. Nevertheless, there is agreement amongst all of these reports that at moderate and high levels of immune challenge, JNK is not required for T cell activation. An important question concerns why T cells are sensitive to defects in JNK1 or JNK2 expression. This may result from the pattern of JNK expression in murine T cells. Immature T cells (thymocytes) express high level of JNK1 and JNK2. However, JNK expression is down-regulated in peripheral T cells. JNK is therefore expressed at low levels in naive T cells, but the expression of JNK is up-regulated following immune challenge. The low level of JNK expression in naive T cells may account for the sensitivity of these cells to targeted disruption of the Jnk genes.

傳統教學法之 態度•勿有傲慢之態度，言 詞應尊重學生。•教師本人須對課程內容有較高之興緻。•導引學生之興趣 (if possible): (1) 談分生歷史， (2) 醫學相關典故

•當大量學生昏睡時： (1) 講笑話或時事評論，(2)問學生問題， (3)下課

教學

設定教學對象 ( 大多數或優秀群 )

選定教學內容 ( 學生未來之需求； 共識之新課程； 傳授學習方法 )

現場教學方式 (勿輕忽傲慢； 一分鐘考卷 )

學習成果檢驗

傳統教學法之成 績評等

筆試 口試

考試方式及內容將導引學生學習方向

考試 報告

書面 口頭

Lecture and Examination

報告方式評等• 優點： (1)增進學生尋找資料， (2) 組織能力，

(3) 表達能 力， (4) 及共同合作能力。• 缺點： (1) 無法涵蓋完整內容，學生易 僅有部份之認知與了解。 (2) 易產生不合 宜之作 弊。

•追蹤考核及和學生討論這 些報告是必須的，學生方能知其不 足，並 改進之。

口試• 教也者，長善而救其失也。─學記• 善問之人，如匠善攻治堅木，先研治其濡易之處，然後砍其節目。─禮記正義

筆試 方式評等•筆試 之問題： 間接延伸推論化 。•筆試 之問題： 多樣化

5‘ Cap of Eucaryotic mRNA

Problem example

• Which of the following ends does NOT contain a free 3’-OH group?

A. 5’ end of a procaryotic mRNA

B. 5’ end of an eucaryotic mRNA

C. 3’ end of a procaryotic mRNA

D. 3’ end of an eucaryotic mRNA

Problem example

• Teaching material: Eucaryotic intron always starts with GU and ends with AG.

• 直接式 Problem: Eucaryotic intron always

A. starts with GA and ends with AG

B. starts with GU and ends with AG

C. starts with AG and ends with UG

D. starts with GU and ends with UG

Problem example

• 間接式 Problem:

• Which of the following DNA sequences may contain an intron?

A.GCAATGTGCATGCGACGTACCTCATACTCTCGATCGATC

B.GCAATGTGCATGCGACGTACCTCATACTCTCGAGCGATC

C.GCAATGCGCATGCGACGTACCTCATACTCTCGATCGATC

D.GCAATGCGCATGCGACGTACCTCATACTCTCGAGCGATC

Problem Example (直接型 )

• The activity of the following enzymes is most likely to decrease as cyclic AMP increases?

A. glycogen phosphorylase

B. glycogen phosphorylase kinase

C. glycogen synthetase

D. Glycogen synthetase phosphatase

Problem example ( 多樣化 )• An infant is admitted to National Cheng Kung University Hospital with a suspected glycogen-storage

disease. A series of tests were performed on a liver biopsy with the following results:

I. Examination of liver glycogen showed an essentially normal structure

II. Examination of the activities of enzymes of glycogen synthesis and breakdown showed them all to be within normal limits.

III. Blood glucose was abnormally low, 12-20 mg/100 ml (normal is about 75 mg/100 ml)

IV. Feeding of glucose resulted in rapid elevation of blood glucose, but there was no increase in blood glucose upon feeding of fructose or galactose (fructose and galactose enter glycolysis at the level of triphosphates and glucose-6-P, respectively)

V. No hyperglycemic effect was observed upon administration of epinephrine or glucagon.

From these observations you could conclude correctly that the enzyme defect in this patient is

A. hexokinase, B. fructose-1,6-diphosphatase, C. glucose-6-phosphatase,

D. hexose-1-P-uridyl transferase, E. adenyl cyclase

教學

設定教學對象 ( 大多數或優秀群 )

選定教學內容 ( 學生未來之需求； 共識之新課程； 傳授學習方法 )

現場教學方式 (勿輕忽傲慢； 一分鐘考卷 )

學習成果檢驗 (間接、多樣化 )

What do we need to do?

1. An integrated education: merging the disciplines2. Education strategy: increasing the involvement of the student in the process of education.3. Changing the examination system: Courses should move away from having too many in-class tests to using other methods of assessing the progress of students, such as laboratory reports that mimic original researchpapers, research reports and presentations, literature reports and topic papers4. A taste of real research5. Using the electronic resources6. Fostering responsibility: students involve in every aspects of integratededucation, students must know where they can learn. 7. Educating the publics.8. From idea to implementation!

References• Edward J. Wood. Biochemistry and molecular biology teaching over the

past 50 years. Nat. Rev. Mol. Cell Biol. (2001) 2: 217-221.• Ellis Bell. The future of education in the molecular life sciences. Nat.

Rev. Mol. Cell Biol. (2001) 2: 221-225.• Academic duty (1997) by Donald Kennedy ( 中文譯本學術這一行 by

楊振富、天下遠見出版社 )• Educational Psychology: A Cognitive Approach (1987) by Richard

Mayer. ( 中文譯本 by 林清山、師範大學教育學院院長、遠流出版社 )

• 當老師的第一本書。鄭義風、王戎 ( 廣西師範大學出版社、正中書局 )