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Study Guide The Cell as Biochemical Machinery

PREFACE
The Block The Cell as Biochemical Machinery (CBM) has been designed for students at the first semester in order to understand the concept about cells. Cell is the smallest unit of the body; grouping with other substances to represent its products to form a bigger unit, called body tissues. Cell is a protoplasm mass with a nucleus, which is lined by a membrane. In particular condition, cell can make assimilation, growth, and reproduction. In this Block, there are three main areas that have to be understood: 1. The structure and function of the cell including plasma membrane, transport of various substances in cell membrane, receptors, organelles and inclusions, nucleus and chromosomes, cytoskeleton, and cell cycle. 2. Introduction to biology molecular and its application in medicine, gene expression, and signal transduction. 3. Cellular responses to injury and death (necrosis and apoptosis). Beside these three areas, this Block also defines about the basic characteristics of cell, and describes about some prominent individuals who have done cell researches, given in the introductory lecture. By understanding the concepts of cell, students are expected to have a sufficient basis for continuing medical studies to further extend their knowledge and skills in the medical sciences. By doing so, students will be able to keep update with the fast progressing medical sciences and technologies and apply them properly in their future medical practice. This Study Guide of The Cell as Biochemical Machinery (CBM) contains learning tasks to be discussed by the students in the small group discussions and individually in order to achieve the block objectives. Other than that, there are overviews of lectures, student project to write and to present a paper, practice, items for self-assessment to evaluate students understanding on the concepts. The Block The Cell as Biochemical Machinery (CBM) is undertaken 20 days including examination. Student-centered learning as the primary approach in the teaching-learning activities with dynamic group discussions are facilitated by tutors. Individual learning on campus and at home is also an important part of the learning process. To develop good understanding of the CBM, learning activities will also be carried out as lectures and practical works.

The Planner Team CBM

Faculty of MedicineUdayanaUniversity, MEU

Study Guide The Cell as Biochemical Machinery

TABLE OF CONTENTS
Preface............................................................................................................. Table of contents .................................................... Learning outcome .................................................. Curriculum content ........................................................................................... Planners Team ................................................................................................... Lectures .............................................................................................................. Facilitators ... ............................... Time Table Class A .................... Time Table Class B... Meeting of students representatives .. Plenary Session Assessment Method.. Student project ................................................................................................... Abstract ............................................................................................................ Task 1 The Structure of the Plasma Membrane and The Transport Mechanism of Various Substances Task 2 Organelles and Inclusions..... Task 3 Cytoskeleton................ .. Task 4 Nucleus and Chromosomes. Task 5 Cell organization in Connective tissue ................................................... Task 6 Cell organization in Epithelial tissue Task 7 Introduction to Molecular Biology ... Task 8 Gene expression ................................................................................. Task 9 Basic feature of enzyme ....................................................................... Task 10 Signal transduction.............................................................................. Task 11 Cell cycle............................................................................................. Task 12 Bioenergetics and oxidative metabolism .. ..... Task 13 Cellular Responses to Injury and Death ... Task 14 Application of molecular biology in medicine ........................................ Task 15 Cellular intervention/therapies ............................................................ Practice. Self Assessment .. Curriculum Map References.. 1 2 3 4 6 6 7 8 13 18 18 18 18 20 31 31 32 33 34 34 34 35 35 36 36 37 37 38 38 40 43 50 51

UdayanaUniversity Faculty of Medicine, MEU

Study Guide The Cell as Biochemical Machinery

~ CURRICULUM ~ THE CELL AS BIOCHEMICAL MACHINERY Aims: To comprehend the molecular mechanisms underlying normal cell function and disorders To apply basic cellular and molecular concepts and principles in dealing with clinical disorders Learning Outcomes: 1. Explain the structure of the plasma membrane and differentiate the transport mechanism of various substances through plasma membrane. 2. Explain the general structure and function of cytoskeleton in relation to endocytosis, pinocytosis, and locomotion. 3. Differentiate functionally cytoplasmic organelles from cytoplasmic inclusions. 4. Explain the general functional structure of cell nucleus. 5. Explain the functional structure of cells organization in various tissues and its clinical implication. 6. Explain the principal mechanisms by which genes control general cell functions and gene expression in normal cells. 7. Explain the enzyme as a protein that regulates metabolism and its function in medical diagnostic. 8. Explain the energy metabolism of the cell and its clinical implications 9. Explain the signaling mechanism underlying cell to cell communication and its clinical or practical implications 10. Summarize cell cycle and its clinical implications. 11. Explain the cellular responses to injury and death (necrosis and apoptosis). 12. Explain applications of molecular biology in medicine 13. Explain pharmacology and pharmacodynamic (action of drugs to the body, mechanism of action)

UdayanaUniversity Faculty of Medicine, MEU

Study Guide The Cell as Biochemical Machinery

CURRICULUM CONTENT 1. The Structure of the Plasma Membrane & the Transport Mechanism of Various Substances a. The molecular structure of plasma membrane b. The transport mechanism of common substances (micro molecules) through the plasma membrane c. The practical and clinical implication of transport substances 2. Organelles and Inclusions a. The basic concept of organelles & inclusion body b. The general principle of post translation modifications on Rough Endoplasmic Reticulum and Golgi Apparatus c. The functional structure of the lysosomes, proteasomes, and peroxisomes d. The mitochondria function underlying energy metabolism e. The clinical implication of the function of proteasomes, peroxisomes, lysosomes, and mitochondria 3. Cytoskeleton a. The components of cytoskeleton b. The mechanism of macromolecules crossing from extracellular to intracellular c. The mechanism of cells product release from intracellular to extracellular d. The common mechanisms of cell locomotion e. The clinical implication of cytoskeleton disorders 4. Nucleus and Chromosomes a. The major components of the cell nucleus b. The structures that compose the nuclear pore complex c. The structures that compose the nucleosome d. The syndromes that has an association to the sex chromosome abnormalities 5. Cell organization in connective tissue a. The components of connective tissue b. The functional structures of connective tissue c. The classification of connective tissue d. The clinical impication of connective tissue 6. Cell organization in epithelial tissue a. Cell-cell and cell-matrix adhesion in assembling into epithelial tissue b. Polarity of epithelium c. The clasification of epithelial tisssue d. The functional structures of epithelial tissue e. The clinical implication of epithelial tissue 7. Introduction to Molecular Biology a. The basic concept of gene, genome, and central dogma b. The functional structure of DNA & RNA c. The molecular mechanism of genetic inherited d. The clinical implication of DNA mutation e. The various mechanism of DNA repair system 8. Gene expression a. The function of three types of RNA b. The definition of genetic code and codon c. The mechanism of transcription d. The mechanism of translation

UdayanaUniversity Faculty of Medicine, MEU

Study Guide The Cell as Biochemical Machinery

9. Basic feature of enzyme a. The concept of enzyme, apoenzyme, coenzyme, and holoenzyme b. The enzyme kinetics 10. Bioenergetics and oxidative metabolism a. Mitochondrial electron transport system b. Mechanism of ATP synthase c. Oxidative phosphorylation inhibitors 11. Signal transduction a. The signaling molecules (ligand) b. The cell receptors c. The variety pathways transduction signals from peripheral cytoplasm to the nucleus by which stimulate inhibit. d. The function of secondary and the third messenger. 12. Cell Cycle a. The basic concept of the cell cycle b. The two major events in cell cycle c. The mechanism of the cell division d. The mitotic and the meiotic cell division e. The process of cell differentiation f. The clinical implication of the cell division and cell differentiation disorders 13. Cellular Responses to Injury & Death a. The mechanisms and causes of cell injury b. The cell adaptation to injury (atrophy, hypertrophy, hyperplasia & metaplasia, sub cellular responses to injury, mechanism of intracellular accumulation and its morphologic and pathologic calcification. c. The general pathways of cellular injury, mechanism of reversible and irreversible injury and its morphologic changes d. The mechanism of apoptosis and its morphologic changes and some examples e. The differentiation necrosis from apoptosis in relation to their causes, mechanisms, and morphologic changes f. The various forms of necrosis with their respective underlying mechanisms of many kind of necrosis such as coagulative necrosis, caseous necrosis, liquifactive necrosis, enzymatic necrosis, fatty necrosis, and gangrenous necrosis. g. The general mechanisms of cellular aging 14. Applications of Molecular Biology in Medicine a. The implications of gene testing b. The advantages of using recombinant vaccine compared with nonrecombinant/conventional c. Reproductive cloning 15. Cellular Intervention/Therapies a. The definition of a drug b. The common route of drugs administration c. The fate of drugs in the body, if taken orally d. The basic concept of pharmacology, Pharmacokinetic, Pharmacodynamic, Volume of Distribution, Half life, Bioavaibility, Minimum Effective Concentration, Therapeutic window, First Pass Effect e. Differences between drug elimination and drug excretion f. Differences between first order elimination and cero order elimination g. The basic concept of agonist drug, antagonist drug, full agonist, partial agonist, Pharmacologic antagonist, competitive, Physiologic antagonist, ED50, LD50, Therapeutic index, efficacy of drug, potency of drugs

UdayanaUniversity Faculty of Medicine, MEU

Study Guide The Cell as Biochemical Machinery

~ PLANNERS TEAM ~

No 1 2 3 4 5

Name dr. IGN Ngr Mayun, Sp.HK (Head) dr. I.A. Ika Wahyuniari, M.Kes (Secretary) dr. Sri Widnyani,Sp.PA dr. Wayan Surudarma, M.Si Prof. dr. Gst Md Aman, PFK

Departement Histology Histology Pathology Biochemistry Pharmacology

Phone 08155715359 08123614856 08123925845 081338486589 081338770650

~ LECTURER ~ No 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Name dr. IGN Ngr Mayun, Sp.HK dr. I.A. Ika Wahyuniari, M.Kes dr. Ni Putu Sri Widnyani, Sp.PA dr. Wayan Surudarma, M.Si dr. IGA Artini, M.Si Prof. dr. Bagiada, Sp.Biok dr. Desak Made Wihandani, M.Kes dr.Komang Januartha Putra Pinatih, M.Kes dr. IGK Nyoman Arijana, M.Si.Med dr. Ni Made Linawati, M.Si dr. IGA Dewi Ratnayanti, S.Ked Prof.Dr.dr.I Nyoman Adiputra, PFK,Sp.Erg. Ni Wayan Tianing, S.Si, M.Kes MOH, Departement Histology Histology Pathology Biochemistry Pharmacology Biochemistry Biochemistry Microbiology Histology Histology Histology Physiology Biochemistry Microbiology Biochemistry Phone 08155715359 08123614856 081337115012 081338486589 08123650481 081338338611 081338776244 08123831710 085339644145 03518617765 03618550344 0811397971 08123982504 08553711398 081337141506

dr. Ni Nyoman Sri Budayanti, Sp.MK Dr. rer. Nat. dr. Ni Nyoman Ayu Dewi, M.Si

UdayanaUniversity Faculty of Medicine, MEU

Study Guide The Cell as Biochemical Machinery

~ FACILITATORS ~
Regular Class
NO 1 2 3 4 5 6 7 8 9 10 11 12 NAME dr. Ni Kadek Mulyantari, Sp PK dr. Dewi Sutriani Mahalini, Sp.A dr. Dudut Rustyadi , Sp.F dr. Nyoman Ratep, Sp.KJ (K) dr. Nyoman Sunerti, Sp.M dr. Putu Anda Tusta Adiputra, Sp.B(K)Onk dr. Ayu Setyorini Mestika Mayangsari, M.Sc,Sp.A dr. Sianny Herawati, Sp.PK dr. A.A.Bagus Ngurah Nuartha, SpS.(K) I.D.A. Pt Rasmika Dewi, S.Si, Apt dr. Ni Made Linawati , MSi dr. Anak Agung Mas Putrawati Triningrat, Sp.M GROUP 1 2 3 4 5 6 7 8 9 10 11 12 DEPT Clinical Pathology Pediatric Forensic Psychiatry Opthalmology Surgery Pediatric Clinical Pathology Neurology Clinical Pathology Anatomy Opthalmology PHONE 08123647413 08123641466 0818651015 08123618861 08123982624 08123826430 081353286780 0818566411 08179782240 081558914941 03618617765 08123846995 ROOM 3 floor: R.3.01 nd 3 floor: R.3.02 nd 3 floor: R.3.03 nd 3 floor: R.3.04 nd 3 floor: R.3.05 nd 3 floor: R.3.06 nd 3 floor: R.3.07 nd 3 floor: R.3.08 nd 3 floor: R.3.19 nd 3 floor: R.3.20 nd 3 floor: R.3.21 nd 3 floor: R.3.22
nd

English Class
NO 1 2 3 4 5 6 7 8 9 10 11 12 NAME dr. Anak Agung Sagung Sawitri, MPH dr. Anak Agung Wiradewi Lestari , Sp PK dr. I A. Ika Wahyuniari, M.Kes dr. Dewa Made Artika , Sp.P Dr. dr. Ketut Suega, Sp.PDKHOM Dr. dr. Bagus Komang Satriyasa , M.Repro Dr. dr. I Dewa Made Sukrama, MSi, Sp.MK(K) Dr. dr. I Wayan Suranadi , Sp.An.KIC Dr. dr. Wayan Sudana, Sp.THT-KL(K) dr Ni Nyoman Metriani Nesa, M.Sc.,Sp.A dr. Elysanti Dwi Martadiani, Sp.Rad. dr. Anak Agung Gde Yuda Asmara, Sp.OT GROUP 1 2 3 4 5 6 7 8 9 10 11 12 DEPT Public Health Clinical Pathology Histology Pulmonology Interna Pharmacology Microbiology Anesthesi ENT Pediatric Radiology Orthopaedi PHONE 0817340145 08155237937 08123614856 08123875875 081338728421 081805368922 081338291965 08223847675 08123987001 081337072141 081805673099 081337870347 ROOM 3 floor: R.3.01 nd 3 floor: R.3.02 nd 3 floor: R.3.03 nd 3 floor: R.3.04 nd 3 floor: R.3.05 nd 3 floor: R.3.06 nd 3 floor: R.3.07 nd 3 floor: R.3.08 nd 3 floor: R.3.19 nd 3 floor: R.3.20 nd 3 floor: R.3.21 nd 3 floor: R.3.22
nd

UdayanaUniversity Faculty of Medicine, MEU

Study Guide The Cell as Biochemical Machinery

TIME TABLE CLASS A (Regular) Day/ date 1 Wed 20 Nov 13 Time 08.00 08.30 08.30 09.00 Activity Introductory block Lecture 1. The Structure of plasma membrane & transport mechanism of various substances Independent learning PPKN Break SGD Student project Plenary Session Lecture 2. Organelles and Inclusions Independent learning Student project SGD Break Plenary Session Lecture 3. Cytoskeleton Independent learning PPKN Break SGD Student project Plenary Session Lecture 4. Cell organization in connective tissue Independent learning PPKN Break SGD Student project Plenary Session Lecture 5. Cell organization in epithelial tissue Independent learning Student project SGD Break Plenary Session Ven ue C C Lecturers A.Bagiada Adiputra

09.00 10.30 10.30 11.30 11.30 12.00 12.00 13.30 13.30 14.00 14.00 15.00 08.00 09.00 09.00 10.30 10.30 12.00 12.00 13.30 13.30 14.00 14.00 15.00 08.00 09.00 09.00 10.30 10.30 11.30 11.30 12.00 12.00 13.30 13.30 14.00 14.00 15.00 08.00 09.00 09.00 10.30 10.30 11.30 11.30 12.00 12.00 13.30 13.30 14.00 14.00 15.00 08.00 09.00 09.00 10.30 10.30 12.00 12.00 13.30 13.30 14.00 14.00 15.00

C DR C C

Lecture Facilitators Adiputra Linawati

2 Thur 21 Nov 13

DR C C C DR C C

Facilitators Linawati Arijana Lecture Facilitators Arijana Ratnayanti

3 Fri 22 Nov 13

4 Mon 25 Nov 13

C DR C C

Lecture Facilitators Ratnayanti Wahyuniari

5 Tues 26 Nov 13

DR C

Facilitators Wahyuniari

UdayanaUniversity Faculty of Medicine, MEU

Study Guide The Cell as Biochemical Machinery

6 Wed 27 Nov 13

08.00 09.00 09.00 10.30 10.30 11.30 11.30 12.00 12.00 13.30 13.30 14.00 14.00 15.00

Lecture 6. Nucleus and Chromosome Independent learning PPKN Break SGD Student project Plenary Session Practicum Explanation of microscopic structure of connective tissue Discussion about microscopic structure of connective tissue Microscopic structure of connective tissue (A1 A6) Microscopic structure of connective tissue (A7 A12) Break Student Presentation

Mayun

C DR C

Lecture Facilitators Mayun

7 Thur 28 Nov 13

08.00 08.30

C DR

Ratnayanti

08.30 09.30 09.30 11.00 11.00 12.30 12.30 13.00 13.00 15.00

LB

Ratnayanti

Adiputra Arijana Linawati Ayu Dewi

08.00 09.00 8 Fri 29 Nov 13 09.00 10.30 10.30 11.30 11.30 12.00 12.00 13.30 13.30 14.00 14.00 15.00 08.00 09.00 09.00 10.30 10.30 11.30 11.30 12.00 12.00 13.30 13.30 14.00 14.00 15.00 08.00 08.30 08.30 09.30 3 Dec 13 09.30 11.00 11.00 12.30 12.30 13.00

Lecture 7. Introduction to molecular biology Independent learning PPKN Break SGD Student project Plenary Session Lecture 8. Gene expression Independent learning PPKN Break SGD Student project Plenary Session Explanation of microscopic structure of epithelial tissue Discussion about microscopic structure of epithelial tissue Microscopic structure of epithelial tissue (A7 A12) Microscopic structure of epithelial tissue (A1 A6) Break

C DR C C C DR C C DR

Lecture Facilitators Ayu Dewi Ayu Dewi Lecture Facilitators Ayu Dewi Wahyuniari

9 Mon 2 Dec 13

10 Tues

LB LB

Wahyuniari Wahyuniari

UdayanaUniversity Faculty of Medicine, MEU

Study Guide The Cell as Biochemical Machinery

13.00 15.00

Student Presentation

Linawati Mayun Ratnayanti Tianing Lecture Facilitators Tianing Wihandani

11 Wed 4 Dec 13

08.00 09.00 09.00 10.30 10.30 11.30 11.30 12.00 12.00 13.30 13.30 14.00 14.00 15.00 08.00 09.00 09.00 11.00 11.00 12.00 12.00 13.30 13.30 14.00 14.00 15.00 08.00 09.00 09.00 10.30 10.30 11.30 11.30 12.00 12.00 13.30 13.30 14.00 14.00 15.00 08.00 09.00 09.00 10.30 10.30 11.30 11.30 12.00 12.00 13.30 13.30 14.00 14.00 15.00

Lecture 9. Enzyme Independent learning PPKN Break SGD Student project Plenary Session Lecture 10. Signal Transduction Independent learning Student Presentation SGD Break Plenary Session Lecture 11. Cell Cycle Independent learning PPKN Break SGD Student project Plenary Session Lecture 12. Bioenergetics and Oxidative metabolism Independent learning PPKN Break SGD Student project Plenary Session

C C DR C C

12 Thur 5 Dec 13

C
DR C C C DR C C

Ratnayanti Wahyuniari Facilitators Wihandani Mayun Lecture Facilitators Mayun Surudarma

13 Fri 6 Dec 13

14 Mon 9 Dec 13

C DR C

Lecture Facilitators Surudarma

15 Tues 10 Dec 13

08.00 09.00 09.00 10.00 10.00 11.30

Lecture 13. Cellular Responses to Injury/Death Independent learning Meeting of student representatives Independent learning SGD Break Plenary Session

Sri Widnyani

Planners team,
Facilitators Facilitators Sri Widnyani

11.30 12.00 12.00 13.30 13.30 14.00 14.00 15.00

DR C

UdayanaUniversity Faculty of Medicine, MEU

10

Study Guide The Cell as Biochemical Machinery

08.00 09.00 16 Wed 11 Dec 13 09.00 10.30 10.30 11.30 11.30 12.00 12.00 13.00 13.00 14.00 14.00 15.00

Clinical application of molecular biology laboratory Student Presentation PPKn

C C C

Budayanti Ayu Dewi Lecture

Break
Discussion about clinical application of molecular laboratory Student Presentation Plenary session Practicum Explanation of microscopic structure of cell injury Discussion about microscopic structure of cell injury Microscopic structure of cell injury (A1 A6) Microscopic structure of cell injury (A7 A12) Break Student Presentation

C
C

Wihandani
Budayanti

17

08.00 08.30 08.30 09.30

Sri Widnyani

C DR
Sri Widnyani

Thur 12 Dec 13

09.30 11.00 11.00 12.30 12.30 13.00 13.00 15.00

LB

Mayun Surudarma Bagiada Januartha

18 Fri 13 Dec 13

08.00 09.00 09.00 10.30 10.30 11.30 11.30 12.00 12.00 13.30 13.30 14.00 14.00 15.00 08.00 10.30 10.30 11.30 11.30 12.30 12.30 15.00

Lecture 14. Application of molecular biology in medicine Independent learning PPKN Break SGD Break Plenary Session Isolation of DNA PPKn Break Student Presentation

C DR C C C C

Lecture Facilitators Januartha Tianing Lecture Sri Widnyani Januartha Artini Artini

19 Mon 16 Dec 13 20 Tues 17 Dec 13

08.00 09.00 09.00 10.30 10.30 12.00 12.00 13.30 13.30 14.00 14.00 15.00

Lecture 15. Cellular intervention/Therapies Independent learning Student project SGD Break Plenary Session

DR C

Facilitators Artini

UdayanaUniversity Faculty of Medicine, MEU

11

Study Guide The Cell as Biochemical Machinery

Wed

18 Dec 13 Thur 19 Dec 13 Notes: C : DR : SGD : LB :

Preparation for Final Test

10.00 14.00

Assessment

Team

Class room (4.014thfloor) Discussion Room Small Group Discussion Lab Bersama (4th floor)

UdayanaUniversity Faculty of Medicine, MEU

12

Study Guide The Cell as Biochemical Machinery

TIME TABLE CLASS B (English Class) Day/ date 1 Wed 20 Nov 13 Time 09.00 09.30 09.30 10.00 Activity Introductory block Lecture 1. The Structure of plasma membrane & transport mechanism of various substances Independent Learning PPKn Break Student Project SGD Plenary Session Lecture 2. Organelles and Inclusions Student project Break Independent Learning SGD Plenary Session Lecture 3. Cytoskeleton Independent Learning PPKn Break Student Project SGD Plenary Session Lecture 4. Cell organization in connective tissue Independent Learning PPKn Break Student Project SGD Plenary Session Lecture 5. Cell organization in epithelial tissue Student project Break Independent Learning SGD Plenary Session Ven ue C C Lecturers A.Bagiada Adiputra

10.00 11.30 11.30 12.30 12.30 13.00 13.00 13.30 13.30 15.00 15.00 16.00 09.00 10.00 10.00 11.30 11.30 12.00 12.00 13.30 13.30 15.00 15.00 16.00 09.00 10.00 10.00 11.30 11.30 12.30 12.30 13.00 13.00 13.30 13.30 15.00 15.00 16.00 09.00 10.00 10.00 11.30 11.30 12.30 12.30 13.00 13.00 13.30 13.30 15.00 15.00 16.00 09.00 10.00 10.00 11.30 11.30 12.00 12.00 13.30 13.30 15.00 15.00 16.00

Lecture

DR C C

Facilitators Adiputra Linawati

2 Thur 21 Nov 13

DR C C C

Facilitators Linawati Arijana Lecture

3 Fri 22 Nov 13

DR C C

Facilitators Arijana Ratnayanti

4 Mon 25 Nov 13

Lecture

DR C C

Facilitators Ratnayanti Wahyuniari

5 Tues 26 Nov 13

DR C

Facilitators Wahyuniari

UdayanaUniversity Faculty of Medicine, MEU

13

Study Guide The Cell as Biochemical Machinery

6 Wed 27 Nov 13

09.00 10.00 10.00 11.30 11.30 12.30 12.30 13.00 13.00 13.30 13.30 15.00 15.00 16.00

Lecture 6. Nucleus and Chromosome Independent Learning PPKn Break Student Project SGD Plenary Session Practicum Explanation of microscopic structure of connective tissue Student Presentation

Mayun

Lecture

DR C

Facilitators Mayun

7 Thur 28 Nov 13

09.00 09.30

Ratnayanti C C Adiputra Arijana Linawati

09.30 11.30 11.30 12.30 12.30 13.00 13.00 14.30 14.30 16.00

Discussion about microscopic structure of connective tissue Break Microscopic structure of connective tissue (B1-B6) Microscopic structure of connective tissue (B7-B12) Lecture 7. Introduction to molecular biology Independent Learning PPKn Break Student Project SGD Plenary Session Lecture 8. Gene expression Independent Learning PPKn Break Student Project SGD Plenary Session Explanation of microscopic structure of epithelial tissue Student Presentation

DR

LB LB C

Ratnayanti Ratnayanti Ayu Dewi

09.00 10.00 8 Fri 29 Nov 13 10.00 11.30 11.30 12.30 12.30 13.00 13.00 13.30 13.30 15.00 15.00 16.00 09.00 10.00 10.00 11.30 11.30 12.30 12.30 13.00 13.00 13.30 13.30 15.00 15.00 16.00 09.00 09.30

Lecture

DR C C C

Facilitators Ayu Dewi Ayu Dewi Lecture

9 Mon 2 Dec 13

DR C

Facilitators Ayu Dewi Wahyuniari

10 Tues 3 Dec 13

C C Linawati Mayun Ratnayanti

09.30 11.30 11.30 12.30 12.30 13.00

Discussion about microscopic structure of epithelial tissue Break

DR

UdayanaUniversity Faculty of Medicine, MEU

14

Study Guide The Cell as Biochemical Machinery

13.00 14.30 14.30 16.00

Microscopic structure of epithelial tissue (B1-B6) Microscopic structure of epithelial tissue (B7 B12) Lecture 9. Enzyme Independent Learning PPKn Break Student Project SGD Plenary Session Lecture 10. Signal Transduction Student Presentation Break Independent Learning SGD Plenary Session Lecture 11. Cell Cycle Independent Learning PPKn Break Student Project SGD Plenary Session Lecture 12. Bioenergetics and Oxidative Metabolism Independent Learning PPKn Break Student Project SGD Plenary Session Lecture 13. Cellular Responses to Injury/Death Meeting of student representative Break Independent Learning SGD Plenary Session

LB LB C C

Wahyuniari Wahyuniari Tianing Lecture

11 Wed 4 Dec 13

09.00 10.00 10.00 11.30 11.30 12.30 12.30 13.00 13.00 13.30 13.30 15.00 15.00 16.00 09.00 10.00 10.00 11.00

DR C C

Facilitators Tianing Wihandani Ratnayanti Wahyuniari

12 Thur 5 Dec 13

11.00 12.00 12.00 13.30 13.30 15.00 15.00 16.00 09.00 10.00 10.00 11.30 11.30 12.30 12.30 13.00 13.00 13.30 13.30 15.00 15.00 16.00 09.00 10.00

DR C C C

Facilitators Wihandani Mayun Lecture

13 Fri 6 Dec 13

DR C C

Facilitators Mayun Surudarma

14 Mon 9 Dec 13

10.00 11.30 11.30 12.30 12.30 13.00 13.00 13.30 13.30 15.00 15.00 16.00 09.00 10.00

Lecture

DR C C

Facilitators Surudarma Sri Widnyani

15 Tues 10 Dec 13

10.00 11.30

Planners team,
Facilitators

11.30 12.00 12.00 13.30 13.30 15.00 15.00 16.00

DR C

Facilitators Sri Widnyani

UdayanaUniversity Faculty of Medicine, MEU

15

Study Guide The Cell as Biochemical Machinery

09.00 10.00 16 Wed 11 Dec 13 10.00 11.30 11.30 12.30 12.30 13.00 13.00 14.00 14.00 15.00 15.00 16.00

Clinical application of molecular laboratory Student Presentation PPKn Break Discussion about clinical application of molecular laboratory Student Presentation Plenary Session Practicum Explanation of microscopic structure of cell injury Student Presentation Discussion about microscopic structure of cell injury Break Microscopic structure of cell injury (B1 - B5) Microscopic structure of cell injury (B6 B10) Lecture 14. Application of molecular biology in medicine Independent Learning PPKn Break Student Project SGD Plenary Session Student Presentation

LB LB C DR

Budayanti Ayu Dewi Lecture

LB
LB

Wihandani
Budayanti

09.00 09.30 17 09.30 11.30 Thur 12 Dec 13 11.30 12.30 12.30 13.00 13.00 14.30 14.30 16.00

Sri Widnyani C C DR Surudarma Bagiada

LB

Sri Widnyani

09.00 10.00 18 Fri 13 Dec 13 10.00 11.30 11.30 12.30 12.30 13.00 13.00 13.30 13.30 15.00 15.00 16.00 09.00 11.30 19 Mon 16 Dec 13 20 Tues 17 Dec 13 11.30 12.30 12.30 13.30 13.30 16.00 09.00 10.00 10.00 11.30 11.30 12.00 12.00 13.30 13.30 15.00 15.00 16.00

Januartha

Lecture

DR C LB

Facilitators Januartha Sri Widnyani Januartha Artini Lecture Tianing Artini

PPKn Break Isolation of DNA Lecture 15. Cellular intervention/Therapies Student project Break Independent Learning SGD Plenary Session

C LB C

DR C

Facilitators Artini

UdayanaUniversity Faculty of Medicine, MEU

16

Study Guide The Cell as Biochemical Machinery

Wed

18 Dec 13 Thur 19 Dec 13 Notes: C : DR : SGD : LB :

Preparation for Final Test

10.00 14.00

Assessment

Team

Class room (4.014thfloor) Discussion Room Small Group Discussion Lab Bersama (4thfloor)

UdayanaUniversity Faculty of Medicine, MEU

17

Study Guide The Cell as Biochemical Machinery

~ MEETING ~
Meeting of the Student Representatives and the facilitators The meeting between block planners team and the student group representatives will be held on Tuesday, 10th December 2013, at 10.00 until 11.30 am at Class room (4.01). In this meeting, all of the student group representatives (approximately 24 students) are expected to give suggestions and inputs or complaints to the team planners for improvement. For this purpose, every student group must choose one student as their representative to attend the meeting.

~ PLENARY SESSION ~
For each learning task, the student is requested to prepare a group report. The report will be presented in plenary session. Lecturer in charge will choose the group randomly. The aim of this presentation is to make similar perception about the topic that has been given.

~ ASSESSMENT METHOD ~
Assessment will be performed on Thursday, 19th December 2013, 09.00 until 13.00 a.m for both Regular class and English class. There are 100 questions for the examination that consist of Multiple Choice Question (MCQ). The borderline to pass exam is 70. The proportion of examination score are: Small group discussion : 5% Paper (student project) : 15% Final exam (MCQ) : 80%

~ STUDENT PROJECT ~
Students have to write a paper with topics that has been given by lecturer. The topic will be chosen randomly on day 1. Each small group discussion is consist of 2 paper with different tittle. Therefore, 1 paper will be wrote by 5-7 students. Students can discuss about content of paper with relevant lecturer. Students can discuss about format of paper with respective facilitator. Students write a paper as student project and will be presented in front of the class. The paper and the presentation will be evaluated by respective facilitator and lecturer. Format of the paper : 1. Cover Tittle Name Student Registration Number Faculty of Medicine, Udayana University 2013 Introduction Content Conclusion References (minimal 3 references) Example : Journal Porrini M, Risso PL. 2011. Lymphocyte Lycopene Concentration and DNA Protection from Oxidative Damage is Increased in Woman. Am J Clin Nutr 11(1):79-84. Textbook 2. 3. 4. 5.

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Abbas AK, Lichtman AH, Pober JS. 2011. Cellular and Molecular Immunology. 4th ed. Pennysylvania: WB Saunders Co. Pp 1636-1642. Note. 5-10 pages; 1,5 spasi; Times new roman 12

Paper Assessment Form Block The Cell as Biochemical Machinery

Name : ........................................... Student Reg. Number : ........................................... Facilitator : ........................................... Title : ........................................... Supervisors (Facilitator) scoring with 60% qualification : No 1. 2. 3 4 Item Assessment Ability to find the literature Communication/Attitude Quality of material Students interest and motivation TOTAL Range Score (%) 0-20 0-30 0-40 0-10 100 Score

Supervisor,

(...........................................) NIP.

Evaluatorsscoring (presentation) with 40% qualification : No Item Assessment 1. Quality of material 2. Capability of information searching 3 Critical thinking TOTAL Evaluator, Range Score (%) 0-60 0-10 0-30 100 Score

(................................................) NIP.

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Topic of Student Project

Regular and English Class No SGD

Title

Evaluator

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

The effect of free radical on cell membrane Glial Fibrillary Acidic Protein in Stroke Patients Role of Vincristine in Treatment of Multiple Myeloma Lysosomal disorders Ribosomal disorders Abnormalities in number of sex chromosomes Abnormalities in number of autosom Connective Tissue Disorder Connective Tissue Disorder Endothelial function and dysfunction The mutation of DNA Repair system and cancer Telomerase and aging Dogma central in molecular biology The role of calcium in nerve transmission The role of DAG in signal transduction The role of cyclin and CDKs in cell cycle Bacterial protein synthetic machinery inhibitors Mithocondrial poisons Enzyme serum in diagnose of diseases Ischemic and hypoxic injury in myocardial infarction Free radicals and cancer PCR in diagnosis of infectious diseases Pharmacology changes in drug response due to chronic drug use The role of genetic factor in the variation of drug response

Adiputra Arijana Arijana Linawati Linawati Mayun Mayun Ratnayanti Ratnayanti Wahyuniari Ayu Dewi Ayu Dewi Ayu Dewi Wihandani Wihandani Mayun Surudarma Surudarma Bagiada Sri Widnyani Sri Widnyani Januartha Artini Artini

Date of presen tation 28 Nov 28 Nov 28 Nov 28 Nov 3 Dec 3 Dec 3 Dec 3 Dec 5 Dec 5 Dec 11 Dec 11 Dec 11 Dec 11 Dec 11 Dec 12 Dec 12 Dec 12 Dec 12 Dec 16 Dec 16 Dec 16 Dec 16 Dec 16 Dec

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~ LEARNING PROGRAMS ~ Lectures

DAY 1: The Structure of the Plasma Membrane & the Transport


Mechanism of Various Substances Lecturer Objective Abstract : Prof adiputra : to understand the structure of plasma membrane :

Every eukaryotic cell is covered by plasma membrane, which separates the extracellular from the intracellular fluid. Plasma membrane is mainly composed of phospholipids bilayer, protein and lesser amount of polysaccharide and cholesterol. The functions of plasma membrane are maintaining cell integrity, as a barrier at membraneplasma and recognizing antigens. Phospholipid Bilayer Membrane Dominant phospholipids component of plasma membrane are phosphatidylcholine, phosphatidylethanolamine, phosphate-dylserine and sphingomyelin. Other phopolipids e.g inositol phospholipids, arachidonic acid phospholipids are present in lesser amount, even though its have important functional value, phospholipids bilayer is said to be amphipathic because it has hydrophilic, hydrophobic nature. Small uncharged and lipid molecules can get through plasma membrane, it is called simple diffusion. Protein Membrane Protein of plasma membrane consists of integral protein (transmembrane protein/multipass protein (fluid mosaic model) and peripheral protein. These proteins have role in selective permeability as facilitated diffusion. Integral protein may function as channel protein, carrier protein. Channel protein could adjust with the across hydrophilic molecule by forming polar inner lining channel, which could be gated channel (ligand-gated channels, voltage-gated channel and G-protein gated ion channel) and ungated channel. Carbohydrate and Cholesterol Membrane Polysaccharide molecule on the outer side of plasma membrane is called glycocalyx, can inform of glycoprotein and glycolipid. It functions in protection. Lecturer : Prof Adiputra Objective: to understand the transport mechanism of various substances through plasma membrane Abstract : Cell membrane separates cytoplasm (intacellular fluid) from its environment (extracellular fluid). Both fluids consist of different substances which are maintained by the existence of cell membrane. Its structure makes the transport of spesific substances occur to support cell life. There are two types of transport mechanism across the cell membrane i.e. passive transport (diffusion) and active transport. The diffusion itself can be differentiated into simple diffusion and facilitated diffusion, with its different mechanism. There are too many factors that can affect diffusion, each of which must be learnt by the students. Active transport can be

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divided inti primary active and with its own character including the substance to be transported and factors that involve. Transport across cell membrane can describe many physiologic processes that take place in different parts of human cells such as intestine epithelium, renalis tubules epithelial, exocrine glands epithel, gall bladder epithel and membrane of choroideus plexus in the brain. All will be learnt in this topic.

DAY 2: Organelles & Inclusion

Lecturer : dr. Ni Made Linawati, M.Si Objective: to differentiate functionally cytoplasmic organelles from cytoplasmic inclusions Abstract : The cytoplasm contains other organelles, which are better visualized with an electron microscope that can view components as small as 2 nm. The organelles include the nucleus, mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomes, peroxisomes, proteasomes, cytoskeleton, and plasma membrane. Mitochondria contain a double membrane; with the inner membrane containing many infolds, referred to as the cristae that contain the machinery for cellular respiration. Mitochondria contain their own mitochondrial DNA and make proteins.The endoplasmic reticulum (ER) consists of flattened sheets, sacs, and tubes of membranes throughout the cytoplasm and is responsible for protein synthesis (rough ER) and lipid metabolism (smooth ER and rough ER). The Golgi apparatus is a stack of flattened membranous sacs involved in the modification and transport of molecules made in the endoplasmic reticulum. The membrane-enclosed Lysosome contains enzymes required for intracellular digestion. Peroxisomes are membrane-bound organelles in which hydrogen peroxide is generated and degraded. Proteasomes responsible for proteolysis of malformed and ubiquitin-tagged protein or antigenic protein have to be cleaved into epitopes. Cytoplasmic inclusion is not always present in every cell. Glycogen is the polymer of simple glucose. Blood glucose metabolized within cell to produce ATP or stored in the glycogen vesicle.Lipid, stored in triacylglycerol form as various sizes of droplets whether as a single and hugedroplet (lipocytes), or small and multiple consisted of ester cholesterol (dominantly within cells that synthesized steroid hormones).Lipofuchsin pigmen is residual bodies that unable to be digested by lysosomes, permanently in nature. The amount become increasingly in number due to the increasing of life span and often existed in nervous cell.

DAY 3: Cytoskeleton

Lecturer Objective Abstract

: dr. IGK Nym Arijana, M.Si.Med : to understand the general structure and function of cytoskeleton in relation to endocytosis, pinocytosis, and locomotion :

The cytoskeleton is a dynamic three-dimensional structure that fills the cytoplasm, acts as both muscle and skeleton. This structure maintains cell shape, protects the cell,

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enables cellular motion (using structures such as flagella, cilia and lamellipodia), and plays important roles in both intracellular transport (the movement of vesicles and organelles, for example) and cellular division. The long fibers of the cytoskeleton are polymers of subunits. The primary types of fibers comprising the cytoskeleton are micro (thin) filaments, microtubules, and intermediate filaments. Thin filaments are fine, thread-like protein fibers, 6 nm in diameter, composed of two intertwined chains of G-actin. Thin filaments are most concentrated just beneath the cell membrane, and are responsible for resisting tension and maintaining cellular shape, forming cytoplasmatic protuberances (pseudopodia and microvillus), and participation in some cellto-cell or cell-to-matrix junctions. Thin filaments are also important for cytokinesis (formation of the cleavage furrow) and, association with myosin responsible for muscle contraction. Actin/Myosin interactions also help produce cytoplasmic streaming in most cells. Microtubules are hollow-like cylindrical structure, 25 nm in diameter. They are composed of subunits of the protein tubulin--these subunits are termed alpha and beta. . They have a very dynamic behaviour, binding GTP for polymerization. They are commonly organized by the Centrosome. Microtubules act as a scaffold to determine cell shape, and provide a set of "tracks" for cell organelles and vesicles to move on. Microtubules also form the spindle fibers for separating chromosomes during mitosis (mitotic spindle). When arranged in geometric patterns inside flagella and cilia, they are used for locomotion Intermediate filaments are about 10 nm diameter and provide tensile strength for the cell. These filaments, are more stable (strongly bound) than actin filaments, and heterogeneous constituents of the cytoskeleton.]Like actin filaments, they function in the maintenance of cell-shape by bearing tension. Intermediate filaments organize the internal threedimensional structure of the cell, anchoring organelles and serving as structural components of the nuclear lamina and sarcomere. They also participate in some cell-cell and cell-matrix junctions. Different types of intermediate filaments are: vimentin, keratin, neurofilaments, lamin, and desmin.

DAY 4: Cell organization in Connective tissue


Lecturer Objective : dr. IGA Dewi Ratnayanthi S.Ked : to understand the functional structure of cells organization in connective tissues and its clinical implication.

Abstract : Most of the cells in multicellular organisms are organized into cooperative assemblies called tissues, which in turn are associated in various combinants to form larger functional units called organs. The four basic tissue types are nerve, muscle, epithelial tissue, and connective tissue. These tissues are found in most organs. As one of the basic tissue, Connective tissue, as its name implies, is a structure that functions to relate and joint other tissue in our body. Therefore, it can be found in every organ or as an organ itself. Beside that bare in its name, connective tissue has many important function, such as support, protection, transportation, storage, and hormone production. As one of the basic tissue, connective tissue may vary in form depending on their components. Connective tissue generally consists of two components, which are cells and extracellular matrix. The main component is fibroblast cell, because it is the major source of the extracellular matrix. Histologically, connective tissue is classified into embryonal and proper connective tissue. Embryonal connective tissue is composed of mesenchym and mucous tissue. These tissues are only found in embryo or umbilical cord. The second type connective tissue is found in mature tissue or organ. It composed of four
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types, which are loose, dense, reticular and adipose tissue. Connective tissue can also be specialized into distinct types of tissue; bone, cartilage, and blood. These types of tissue will be independently discussed on the regard block.

DAY 5: Cell organization in Epithelial tissue

Lecturer Objective

: dr. Ida Ayu Ika Wahyuniari, M.Kes : to understand the functional structure of cells organization in epithelial tissues and its clinical implication. Abstract : All tissues are composed of cells and an extracellular matrix. As one of the basic tissue, epithelial tissue, are principally cellular in composition, although a small amount of extracellular matrix is present, called basal lamina. Cells in epithelial tissues can adhere to one another (cell-cell adhesion) and adhere to components of extracellular matrix/basal lamina (cell-matrix adhesion) through specialized integral membrane proteins called celladhesion molecules (CAMs) that often cluster into specialized cell junctions, such as occluding junction (tight junction), anchoring junction (zonula adherens, desmosomes, hemidesmosomes), and communicating junction (gap junction). Epithelial tissue is present in two forms : as sheets of contiguous cells (epithelia) and as glands. The function of epithelial tissues are protection, transcellullar transport, secretion, absorption, selective permeability, and detection of sensations. These function is related to the morphology of epithelial cells.

DAY 6: Nucleus & Chromosomes


Lecturer Objective : dr. IGN Mayun, Sp.HK : to understand the general functional structure of cell nucleus and chromosome Abstract : The nucleus is the largest organelle of the cell. where the size, shape of the nucleus are generally constant for particular cell type. The nucleus is usually spherical and is centrally located in the cell. Each cell usually has a single nucleus, some cells possess several nuclei ( such as osteoclast) , where mature red blood cells have extruded nuclei. The nucleus contains nearly all of DNA (deoxyribonucleic acid) for RNA (ribonucleic acid) synthesis. It has nucleolus for the essembly of ribosomal subunits. The nucleus bounded by two lipid membranes, houses three major components: - Chromatins. The genetic material of the cell - The nucleolus, the center for ribosomal RNA ( r RNA ) synthesis - Nucleoplasm, containing macromolecules and nuclear particles involved in the maintenance of the cell. Nuclear envelope is composed of two parallel unit membranes that fuse with each other at certain regions to form perforation known as nuclear pore.

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DAY 7: Introduction to Molecular Biology

Lecturer : Dr. rer. Nat. dr. Ni Nyoman Ayu Dewi, M.Si Objective : to understand the principles mechanisms by which genes control general cell functions Abstract : The term genome comes from gene and chromosome. Genome is the entire DNA of one species. Human Genome Project (HGP) is a project to find out the total DNA ofhuman. Part of DNA in chromosome which has a special function is called gene. Recently, only about 5% of genome is identified as gene. According to their location, we identify 2 kinds of DNA i.e. nuclear DNA (n-DNA) and mitochondrial DNA (mt-DNA). Recent researches have focused on mtDNA because of its special characteristic (small molecule, prone to get mutation and its maternal inheritance characteristic). Molecular mechanism of inheritance involves a process known as replication in which parental DNA is divided into two DNA progenies by semi conservative mechanism. An error which happens in replication process will repair through DNA repair system. Central dogma explains how the DNA can act as a messenger molecule which carries the inheritance characteristic [DNA (replication) transcription translation]. Gene expression requires two processes i.e. transcription and translation. DNA is transcribed into 3 forms of RNA i.e. mRNA, tRNA, dan rRNA which involved in translation process (protein synthesis). mRNA will acts as a template for protein synthesis. tRNA contains the anticodon that recognizes the codon in mRNA corresponding to the amino acid it carries and several rRNA associate with a large number of proteins to form the small and large ribosomal subunits. Codon is a three-base sequence in mRNA, are arranged to form amino acid which sequence is inherited from the parental. As we know, there are 4 bases so we have 64 codons (43) consist of 61 generating codons and 3 stop codons. The genetic code stand for 20 amino acids, it means that 1 amino acid can be coded by more than 1 codon. Genetic code is almost universal for both nDNA inti and mtDNA, wirh several exception: AGA and AGG encode for arginin in nDNA but act as stop codon in mtDNA, UGA code for stop codon in nDNA but encode tryptophan in mtDNA.

DAY 8: Gene Expression

Lecturer : Dr. rer. Nat. dr. Ni Nyoman Ayu Dewi, M.Si Objective : to understand the principles mechanisms of gene expression in normal and abnormal cells Abstract : Gene expression is the process by which a gene is decoded and its information is used to produce polypeptide or RNA molecule. A cell uses some of the information encoded by DNA to manufacture protein. To do this, first the process of transcription copies a particular part of the DNA sequence of a chromosome into an RNA molecule that complement to one strand of the DNA double helix. Then the process of translation uses the information copied into messenger RNA (mRNA) to manufacture a specific protein by aligning and joining the specified amino acid. Messenger RNA is a template of protein synthesis where sequences of codon are present. There are 64 codons stand for 20 amino acids. The protein synthesis is started by initiating codon and will be lasted by stop codon. Many kind of protein are produced in our body. Each has a specific function.
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DAY 9: Basic Feature of Enzyme

Lecturer : Ni Wayan Tianing, S.Si., M.Kes Objective : to understand the enzyme as a protein that regulates metabolism and its function in medical diagnostic. Abstract : Gene encodes the information that determines the structure of protein. In turned the protein structure determines its biological activity. Through the biological of protein inthe cells physiological role is determined. Protein are the most abundant and vital organic molecule of the cells. Why? Its cause by great variety of protein functions in the physiological activity of the cell. Protein are capable assuming so many roles, because their structure can vary enormously, depend on the variation of amino acids sequence of the molecule. One of the important roles of protein is act as an enzyme. Another is receptor, and transport protein such as hemoglobin, transferin, immunoglobin, etc. Thus enzyme is a specific protein catalyst, because its catalyst only limited, usually one kind of reaction. Non protein catalyst can catalyst many kind of reactions (H+, OH-). The complete enzyme called holoenzyme. Holoenzyme consists of apoenzyme and coenzyme. Some factors influencing the velocity of the reactin (such as enzyme concentration, substrate concentration, pH, temperature, some inhibitor substance, etc).Many drugs and poisons irreversibly inhibit enzymes. Measuring of activity level of enzyme in serum can help physician in more accurate diagnose of diseases. The nonfunctional of enzyme serum activity are more important for above purpose.

DAY 10: Signal Transduction


Lecturer : dr. Desak Made Wihandani, M Kes. Objective : to understand the signaling mechanism underlying cell to cell communication & its clinical or practical implications Abstract : Signal transduction pathways allow cells to respond to their environment and to change their behavior accordingly. Signals are sensed by a receptor and changed in their form so that they can exert their final effect on the cell. Signals take a variety of forms, but for our purposes there only two. The first type are signals that go into the cell, bind to internal receptors and excert their effects.Steroid hormones, vitamin D, thyroid hormone, and retinoids are the only members of this class. All of the intracellular receptors ultimately activate the transcription of regulated genes. The common feature of signals that enter the cell is that they are small lipophilic molecules that can across the cell membrane. All the other signals exert their effects by binding to extracellular receptor and initiating a cascade of signaling events. They work by activating a phosphorylation cascade and/or the release of second messengers in the cell. Receptors recognize a signal molecule and transmit the signal by activating a downstream signaling pathway. Cytosolic receptors are soluble, cytoplasmic proteins (signal must get inside). The signal grosses the membrane and activates gene transcription. Transmembrane receptors span a membrane (signal outside, response outside). This signal activates a channel, an enzyme, or a G-protein cascade.

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DAY 11: Cell Cycle

Lecturer : dr. I G N Mayun, Sp.HK Objective : to understand normal and abnormal cell cycle and its clinical implications Abstract : The cell cycle is a series of events within the cell that prepare the cell for dividing into two daughter cells. The cell cycle is divided into two major events: interphase and mitosis. Interphase period is a longer period of time and take place 95% of cycle, while mitosis, a shorter period of time and take place 5% of cycle. The capability of the cell to begin and advance through the cell cycle is governed by the presence and interactions of a group of related proteins known as cyclin, with specific cyclin dependent kinase (CDKs). In interphase period, occur replication of genetic material and the cell increases its size. Interphase is subdivided into three phases: G1 (Gap) phase, when the synthesis of macromolecule essential for DNA duplication begins; S (synthesis), when the DNA is duplicated; and G2 phase, when the cell undergoes preparations for mitosis. There are some cells able to undergo mitosis permanently (e.g., muscle cells, neurons), while temporarily (e.g., lymphocytes) will return to the cell cycle at a later time. Cell that have left the cell cycle are said to be in a resting stage, the G0 or the stable phase. Cell division can occur by mitosis and meiosis. Mitosis is cell division that result in the formation of two daughter cells whose chromosome number is equal from theparental chromosome number (diploid), while meiosis will give rise daughter cells whose chromosome number is reduced from the diploid (2n) to the haploid (1n) number (1/2 from mother chromosome number). The process of mitosis is divided into five stage: prophase, prometaphase, metaphase, anaphase, an telophase; while in meiosis consist of two events: meiosis I and meiosis II. The last stage of cell division is cytokinesis.

DAY 12 : Bioenergetics and Oxidative Metabolism

Lecturer : dr. Wayan Surudarma, M.Si Objective : to understand the bioenergetics and oxidative metabolism Abstract : Oxidation of metabolic fuels is essential to life. In higher organisms, fuels, such as carbohydrates and lipids are metabolized to carbon dioxide and water. Most metabolic energy is provided by oxidation-reduction reactions in mitochondria. This is no small feat, because warm-blooded animals have such variable demands for energy from such processes as thermogenesis at low temperatures, stimulation of ATP synthesis during stress, degradation of excess food, efficient use of nutrients during starvation, and coupling of ATP synthesis with the rate of respiration. This topic will provide an introduction to the concept of free energy, oxidative phosphorylation and the transduction of energy from fuels into useful work. The pathways and specific molecules through which electrons are transported to oxygen and the mechanism of generation of ATP will be described and related to the structure of the mitochondrion, the powerhouse of the cell and the major source of cellular ATP. Lastly, these biochemical processes will be applied to human health and disease.

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The electron transport system consists of at least eight major electron carriers that are located in the inner mitochondrial membrane, each of which is isolable as a complex or as a single molecule. Electrons from four major flavoproteins feed electrons to ubiquinone, the first member of the common pathway. Energy derived from the conductance of electrons through the electron transport system is used by three of the complexes to pump protons into the intermembrane space, creating an electrochemical gradient or proton motive force. The proton gradient is used to power ATP synthase for synthesis of ATP by rotary catalysis. Numerous toxins can severely impair the electron transport system, the ATP synthase and the translocase that exchanges ATP and ADP across the inner mitochondrial membrane. The rate of ATP production by the electron transport system is regulated by modulation of the proton gradient, by allosteric modification and phosphorylation-dephosphorylation and by thyroid hormones. At least five uncoupling proteins (UCP) with specific tissue distributions occur in the inner mitochondrial membrane, and they all regulate the membrane potential and thermogenesis. Chronic diseases or conditions, such as diabetes, cancer, obesity, and aging all have metabolic links to dysregulation of oxidative phosphorylation through effects on electron transport system and ATP synthase.

DAY 13: Cellular Responses to Injury & Death


Lecturer : dr. Sri Widnyani, Sp.PA Objective : to understand the cellular responses to injury and death (necrosis and apoptosis) Abstract : Cells are active participants in their environment, constantly adjusting structure and function to accommodate changing demands and extracellular stresses. Cells tend to preserve their immediate environment and intracellular milieu within relatively narrow range of physiologic parameters. As cells encounter physiologic stresses or pathologic stimuli, they can undergo adaptation, achieving a new steady state and preserving viability. If the adaptive capability is exceeded, cells injury develop. Within certain limits, injury is reversible, and cells return to a stable baseline; however with severe or persistent stress, irreversible injury results, and the effected cells die. In this topic, student will learn the causes of cell injury and the mechanisms by which they exert their effects, cellular and sub cellular adaptation to injury, morphology of injured cells, apoptosis, and cellular senescence.

DAY 14: Applications Of Molecular Biology In Medicine


Lecturer : dr. Komang Januartha, M.Kes Objective : Explain applications of molecular biology in medicine Abstract : Following the advancement of science and technology, medical science also reaches its molecular state. Genetic, genomic and proteomic open the way to a new deeper understanding about processes inside the human body, and provide more accurate intervention tools when disturbance in body function occur. Scientists believe that all diseases have genetic component, whether it is inherited or as a body response against environmental stress. Therefore, genetic plays an important role in prevention, diagnosis and therapy for infectious and non-infectious diseases.

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Molecular medicine is the clinical application of molecular biology for prevention, diagnosis and treatment of diseases, both infectious and non-infectious. Molecular medicine can be used to increase the accuracy of diagnostic method, detection of predisposed genetic disorders, designing new drugs based on molecular information, gene therapy, and development of DNA-vaccine and also in forensic medicine. Testing for inherited diseases and susceptibilities will become standard practice as health care becomes increasingly individualized. Tests that detect specific variations in genetic material will enable physicians to select treatments that a person can tolerate and that are the most likely to be effective. Genetics impacts our lives in diverse ways. Genetic tests serve many purposes. They are widely used to screen newborns for a variety of disorders. Often this information enables the doctors to minimize the damage caused by the mutation. In oncology, doctors use gene testing to diagnose cancer, to classify cancer into subtypes, or to predict a patients responsiveness to new treatments. Much of the excitement today centers on gene expression profiling that use a technology called microarrays. A DNA microarray is a thin-sized chip that has been spotted at fixed locations with thousands of single-stranded DNA fragments corresponding to various genes of interest. A single microarray may contain 10,000 or more spots, each containing pieces of DNA from a different gene. Fluorescent-labeled probe DNA fragments are added to ask if there are any places on the microarray where the probe strands can match and bind. Complete patterns of gene activity can be captured with this technology. Genes, which are carried on chromosomes, are the basic physical and functional units of heredity. Genes are specific sequences of bases that encode instructions on how to make proteins. Although genes get a lot of attention, its the proteins that perform most life functions and even make up the majority of cellular structures. When genes are altered so that the encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is a technique for correcting defective genes responsible for disease development. Researchers may use several approaches for correcting faulty genes.

DAY 15: Cellular intervention/therapies

Lecturer : dr. IGA Artini, M.Si Objective : to understand pharmacology, and pharmacodynamic (action of drugs to the body, mechanism of action) Abstract : Drugs are agents that are used for diagnosed diseases, prevent diseases, treat disease, rehabilitation, and prevent pregnant. The action of drugs on the body or the effects of drugs on biologic systems is call pharmacodynamic. Most drugs exert their specific effects in the body by forming a bound with some cellular constituent known as receptor. Drugs that interact with receptor and have intrinsic activity, and elicit a response are termed agonists, but drug that interact with receptor and has no intrinsic activity and preventing response are referred as antagonists. Not all drug actions are mediated by receptor. Volatile anesthetics, metal chelating agents, osmotic diuretic, allopurinol exert their effects that are not mediated by specific receptor. When the response is measured against increasing drug concentration, the graph of the response and concentration is called a graded dose-response curve. Increasing the dose, increasing the response, until some time the response can not increase although the dose is increased. This response is called maximal effect or maximal efficacy or efficacy. The smaller the dose to achieve the maximal efficacy, the greater the potency of the drug. Even all known source of variation are controlled, drug effects are never identical in all patients.
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The fact that a range of doses is required to produce a specified intensity of effect in all individual. The dose of a drug required to produce a specified effect in an individual is termed the individual effective dose. The dose of drug required to produce a specified intensity of effect in 50% of individuals is known as the Median effective dose (ED50). If death is the end point, the ED50 is termed the Median lethal dose (LD50). There are individuals who are unusually sensitive or unusually resistant to a drug or a drug produces an unusual effect. If a drug produces its usual effect at unexpected low dosage, the individual is said to be hyper reactive (not hypersensitive). If a drug produces its usual effect only at unusually large dosage, the individual is said hypo reactive. Decreased sensitivity is also described as tolerance. Tolerance that develops rapidly after administration of only a few doses of a drug is termed tachyphylaxis. An unusual effect of a drug (not dose dependence), that occurs in only a small percentage of individuals is often termed idiosyncracy.

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Learning Task
LECTURE 1

THE STRUCTURE OF THE PLASMA MEMBRANE & THE TRANSPORT MECHANISM OF VARIOUS SUBSTANCES Learning Task (Fawcett & Gartner; Guyton & Ganong) 1. Describe the structure and function of plasma membrane! 2. The composition of intra-cellular fluid and extra-cellular fluid is different! Why it happen? How cells regulate it? 3. Describe the mechanism of types of diffusion and example of substances diffused through cell membrane! 4. Describe the mechanism of type of active transport, and example of substances actively transported through cell membrane! 5. Describe the difference between the co-transport and counter-transport! 6. Describe the active transport through cellular sheets occurs at many places in the body!

LECTURE 2

ORGANELLES AND INCLUSIONS Learning task (Gartner) Vignette A new born baby was died because of deficiency in -galactosidase enzyme. 1. Please describe the structure of organelle involved in this disorders. 2. Please describe the structure of the organelles that involves in protein syntesize! 3. Please describe the functional structure of the organelle that involve in post translation modification ! 4. Please describe the structure of the organelle that involve in ATP synthesize and in which part of the organelle the process of ATP occur ?

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LECTURE3

CYTOSKELETON Learning task 3 (Fawcett & Gartner; Guyton) Vignette 1 A woman, 40 years old come to Hospital complains with mass in her right breast. Anamnesis and physical examination is performed, supported by histopathology and laboratory test. Finally, the diagnosis is breast cancer but the cancer hasnt yet disseminate into other organs (metastasis). In other to follow up the progression of the cancer, mRNA of keratin 19 in patients bloodd is monitored as a biomarker. Learning Task 1. Keratin 19 is a part of cytoskeleton, which one and what is the function? (microfilaments, intermediate filaments, or microtubules) 2. Keratin 19 is expressed in mainly epithelial cell as cytoskeleton, what is the logic keratin 19 can be also used as biomarker for metastasis in breast cancer? Vignette 2 A man, 48 years old come to Hospital complains headache, vomiting since several months ago. Anamnesis and physical examination is performed, supported by histopathology and laboratory test. Using immunohistochemistry staining, it reveals that GFAP expression is increasing. Finally, the diagnosis is astrocytoma (a type of brain cancer). Learning Task 1. GFAP is a part of cytoskeleton, which one and what is the function? (microfilaments, intermediate filaments, or microtubules) 2. What is the logic GFAP expression is increasing in astrocytoma?

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LECTURE 4
CELL ORGANIZATION IN CONNECTIVE TISSUE

Learning Task (Gartner) A 7 year-old child is brought to the hospital for examination and visum et repertum due to several bone fractures found in his extremities. The parents refuse to admit of child abuse. They said that the child is very fragile, a slight bump or falling could made such fracture to their son. These had been happened since he was a baby; therefore their son extremities were not as straight as normal children. From the examination it was found that the child was suffered from Osteogenesis Imperfecta. A low impact, which normally has no effect to non-sufferer, can cause fracture to this patient. 1. Explain about the component of connective tissue that secretes the fiber involved in the case above! A 35 year-old man was submitted to the hospital due to abrupt thoracic pain. From the examination he was found to have a heart murmur and further investigation showed aortic dilatation and mitral valves prolapsed. The man had a tall-lean figure with pigeon chest, arachnodactily, positive thumb and wrist sign, and joint laxity. The patient finally passed away due to aortic dissection. He was diagnosed of having Marfan Syndrome. 2. Explain about the components of connective tissue involved in the case above! A 55 year-old woman wanted to have a more youthful appearance and particularly complained about deep line that run along her nose and corner of her mouth, on her fore head, and eye tip. The aesthetic doctor suggested her to take dermal filler treatment. The procedure was done by injecting substance under the skin to fill the groove that resulted from loss of volume and elasticity due to aging. The substance is also used in osteoarthritis treatment to add on intra articular fluid. 3. Explain about the components of connective tissue involved in the case above! 4. Explain the other components of connective tissue! 5. Please describe the functions of connective tissue and which component/s contributes to each function! 6. Describe the organization of cell into connective tissue! 7. Describe the classification of connective tissue! 8. Differentiate the following types of connective tissue, based on components (cells, ground substance, fiber) and arrangement: a. Dense connective tissue and loose connective tissue b. Dense regular and dense irregular connective tissue c. Dense regular collagenous and elastic connective tissue d. White adipose tissue and brown adipose tissue

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LECTURE 5
CELL ORGANIZATION IN EPITHELIAL TISSUE Vignette : A 60 year old man complained black lump at his right forehead that becomes larger and darker. The doctor diagnosed it as skin cancer from epithelial cells. Cancer has already metastasized to regional lymphnode from examination. A metastasize can occur if adhesion to neighboring cells in an epithelium is disrupted because of loss of E-chaderin expression. The ability to burrow through tissues seems to depend on the production of proteolytic enzymes that can break down basal lamina. Learning Task (Gartner and Goodman) 1. What is Cadherin? Explain its role in cell-cell adhesion of epithelium! 2. Basal lamina is an extracellular matrix. Explain macromolecule components of the extracellular matrix in epithelium! 3. Summarize about cell-cell and cell-matrix adhesion in assembling into epithelium! 4. Differentiate the structure and function of cell junctions in epithelium! 5. Explain the classification of epithelium & glands and its sample location! 6. Explain the clinical correlation of epithelial tissue!

rsday LECTURE 6

NUCLEUS & CHROMOSOMES

Learning task (Gartner; Strachan & Read) 1. Describe the composition of the nucleus, and its envelope! 2. Describe the nuclear pore, and its role in the cell! 3. Describe the nuclear pore complex ! 4. Explain about the chromatin! How many types of chromatin that you know ? 5. Describe about the sex chromatin !

LECTURE 7

INTRODUCTION TO MOLECULAR BIOLOGY

Researchers from German Cancer Research Centerand Essen University Hospital Germany unravelled the cause of malignant melanoma. They found an identical mutation in the gene for telomerase, an enzyme often called immortality enzyme. Telomerase protects the ends of chromosomes from being lost in the process of cell division and, thus, prevents that the cell ages and dies. The inherited gene mutation leads to the formation of a binding
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Study Guide The Cell as Biochemical Machinery

site for protein factors in the controlling region of the telomerase gene, causing it to become overactive. As a result, mutated cells overproduce telomerase and hence become virtually immortal. (Susanne Horn, Adina Figl, P. SivaramakrishnaRachakonda, Christine Fischer, Antje Sucker, Andreas Gast, Stephanie Kadel, Iris Moll, Eduardo Nagore, Kari Hemminki, Dirk Schadendorf and Rajiv Kumar: TERT Promoter Mutations in Familial and Sporadic Melanoma. Science 2013, DOI: 10.1126/science.1230062). To have a better understanding on above information, you need to discuss the following tasks: 1. Definition of chromosome, gene, genome, central dogma in molecular biology, and mutation. 2. Mechanism of DNA replication. 3. Role of telomerase in DNA replication process. 4. Define about point mutations. Distinguish between transition and transversion. 5. Compare the differences between mutation caused by UV radiation and X-rays. How do the DNA repair systems fix it?

LECTURE 8

GENE EXPRESSION Learning Task (Baynes, J.W. and Dominiczak, M.H. Medical Biochemistry) Thalassemias are common world-wide causes of anemia. Often, however, DNA sequencing of the exons of the -globin genes reveals no abnormal nucleotides, but the -globin mRNA is smaller than expected. The hemoglobin produced is defective. 1. 2. 3. 4. 5. 6. How do you define gene expression? Explain about types of RNAs and their function. Describe major steps of transcription. Describe major steps of translation. Define codon, anticodon, stop codon and start codon. How might genetic mutations lead to such abnormal gene expression as the above case?

LECTURE 9

BASIC FEATURE OF ENZYME Vignette A sixty five years old woman came to doctor complaining pain on her left breast. She had her self breast examination (SADARI technique). After doctor examination she diagnosed as breast cancer stadium IIA. The doctor gave metrotrexate as one of the medicine for cancer.

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Leraning Task 1. What is plasma enzyme and what is functional and non functional plasma enzyme? 2. What is coenzyme? Give some examples! 3. What is an active site and function of active site? 4. What is Michaelis constant. Give the reason about Michaelis Menten or Km!. 5. What is competitive inhibitors and non competitive inhibitors. Give some examples in an application! 6. What is the role of metrotrexate in the case above?

LECTURE 10

SIGNAL TRANSDUCTION Vignette: A 23 year-old man presents to the emergency room complaining severe diarrhea. Base on the result of the examination, the diagnose of that patient is Cholera. As the doctor known, cholera is caused by Vibrio Cholera that exert their toxin and bind covalently to the Gprotein receptor. Learning Task 1. Explain about signals and its classification! 2. Explain about receptors and its classification! 3. Describe G-protein-coupled receptors! 4. Outline the activation of downstream intracellular signaling cascades by heterotrimetric G-proteins 5. Explain the mechanism of diarrhea caused by V. cholera! 6. Expalin about the role of calcium as a second messenger!

LECTURE 11
CELL CYCLE Learning task (Gartner) 1. Describe about the cell cycle! 2. How do you sub divided the interphase in cell cycle! 3. Describe the role of the protein cyclin in continuing the cell cycle process! 4. Describe about the mitosis! 5. Compare the mitosis and meiosis cell division! 6. Describe the clinical correlations of mitosis and the cell cycle!

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LECTURE 12

BIOENERGETICS AND OXIDATIVE METABOLISM Vignette A 16-year-old boy presented with headache, seizures and visual loss. There was a long history of inability to exercise due to muscle weakness. There have been episodes of hemianopia and mild hemiparesis lasting several days. His maternal aunt had a similar illness. Accumulation of lactate during and after exercise suggested a defect in mitochondrial oxidative metabolism. Muscle mitochondria were isolated for study. Respiratory Complex I activity was reduced. A point mutation in mitochondrial DNA was identified. Learning Task (Harper) 1. What is the diagnosis of the patient above? 2. Outline the mitochondrial electron transport system showing eight major electron carriers. Vignette An unresponsive 25-year-old woman is carried into the emergency room by her boyfriend, because after taking two doses of 'weight loss' pills, she complained of headache, fever, chest pain, profuse sweating, and weakness. Initial findings were: rectal temperature, 40.8 C (105.5 F), pulse 151 beats per minute, respiratory rate, 56 per minute, blood pressure 40/10. In 15 minutes she died and could not be resuscitated. After death, rigor mortis set in after 10 minutes and her temperature rose to 46 C (115 F) in 10 additional minutes. It was found that she was a body builder and that she took 'weight loss' capsules purchased from a friend, because she wanted to have a leaner body for a show. Among her personal effects, was a plastic bottle containing capsules that proved to contain 2,4dinitrophenol. Learning Task 1. How does 2,4-dinitrophenol act as poisons? 2. Explain the mechanism of ATP synthase! 3. What is the role of uncoupling proteins?
4.

LECTURE 13

CELLULAR RESPONSES TO INJURY AND DEATH Vignette A 60 year old man died after treated in intensive care unit because of hemorrhagic hypertensive encephalopathy. At autopsy, the heart weighted 580 gram and showed marked left ventricular hypertrophy, coronary arterial atherosclerosis, and focus scar in myocard. The brain showed massive bleeding in right temporal lobe and tonsilar herniation. The liver showed yellowish fatty liver and the prostate was enlarge about twice normal size.

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Learning Task (Robbins & Kumar) 1. List abnormal adaptation process, cell injury, and abnormal material accumulation occurred in this patient 2. Describe their morphologic appearance. 3. Explain pathogenesis of myocardial hypertrophy 4. Explain mechanisms of cell death in this condition 5. Explain pathogenesis of fatty liver

LECTURE 14

APPLICATIONS OF MOLECULAR BIOLOGY IN MEDICINE

Learning Task (Gene Therapy and Genetic Counseling) 1. Describe the implications of gene testing regarding to social and ethical issues! 2. What are the advantages of using recombinant vaccine compared with nonrecombinant/conventional one? 3. What is your opinion about reproductive cloning? Is it legal or illegal?

DAY 15

CELLULAR INTERVENTION/THERAPIES

Learning task (Katzung & Trevor) 1. Learn the term: Receptor, Effector, Agonist drug, Full agonist, Partial agonist, Pharmacologic antagonist, Competitive antagonist, Irreversible antagonist (Non Competitive antagonist, Physiologic antagonist, Chemical antagonist, Graded doseresponse curve, Quantal dose-response curve, ED50 (Effective Dose 50), LD50 (Lethal Dose 50), Therapeutic Index, Efficacy, Potency. 2. Compare the efficacy and the potency of two drugs on the basis of their doseresponse curves. 3. Describe about tolerance, hyperreactive, hyporeactive, and idiosyncrasy!

Vignette The trial of two antihypertensive drug (A & B) were studied in a group of population, and the percentage of the group showing a specific effect (can decrease 20 mmHg systolic pressure) were determined.

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Study Guide The Cell as Biochemical Machinery

The results of the study are as below. Dosage percentage responding percentage responding to drug A to drug B -----------------------------------------------------------------------------------------------------------12.5 mg 1 10 25 mg 10 50 37.5 mg 50 70 50 mg 90 100

Can you define: Efficacy of drug A and B ED50 of drug A and B LD50 of drug A and B Therapeutic index of drug A and B Potency of drug A and B

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PRACTICE Practice 1: Cell Organization in Connective Tissue Objective : to increase understanding about Connective Tissue Date and Place : Thursday, 28th November 2013 Lab Bersama (4th floor) Facilitator : dr. IGA Dewi Ratnayanti, S.Ked Materials : Microscope, Microscopic preparations about : A. Embryonal connective tissue a. Mesenchymal connective tissue b. Mucoid connective tissue B. Proper connective tissue a. Loose connective tissue i. Adipose connective tissue ii. Limphoreticular connective tissue iii. Areolar connective tissue b. Dense connective tissue i. Elastic connective tissue ii. Collagen connective tissue

Practice 2: Cell Organization in Epithelial Tissues Objective : to increase understanding about Epithelial Tissue Date and Place : Tuesday, 3rd December 2013 Lab Bersama (4th floor) Facilitator : dr. Ida Ayu Ika Wahyuniari, M.Kes Materials : Microscope, Microscopic preparations about : A. Epithelium a. Stratified epithelium b. Simple epithelium c. Pseudostratified epithelium d. Transtitional epithelium B. Glands a. Serous glands b. Mucous glands c. Mixed glands

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PRACTICE 3 : Cellular Responses to Injury and Death Objective : to increase understanding about cellular responses to injury and death Date and Place : Thursday, 12th December 2013 Lab bersama(4th floor) Facilitator : dr. Sri Widnyani, Sp.PA (K) Materials : Microscope, Microscopic preparations about : A. Cell Adaptation 1. Atrophy 2. Hypertrophy 3. Hyperplasia 4. Metaplasia B. Reversible injury 1. Cellular swelling 2. Fatty change C. Cell death 1. Necrosis a. Coagulative necrosis b. Liquefactive necrosis c. Caseous necrosis d. Enzymatic necrosis 2. Apoptosis D. Intracellular & ekstracellular acummulation 1. Lipids a. Steatosis b. Cholesterol 2. Hyaline change 3. Pigmen a. Melanin b. Carbon E. Pathologic calcification 1. Dystrophic calcification 2. Metastatic calcification

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Practice 4: Isolation of DNA Objective : to increase understanding about DNA isolation Date and Place : th Monday,16 December 2013 Lab bersama (4th floor) Facilitator : Ni Wayan Tianing, S.Si, M.Kes.

DNA Isolation Procedure from Whole Blood (Genomic DNA Extraction) 1. Add 12 ml blood + 36 ml (3 times blood volume) 1X RBC solution to a 50 ml Falcon centrifuge tube. Invert the tube 2-3 times during the preparation. Incubate the sample for at least 10 minutes at room temperature. Do not allow the sample to sit in the RBC lysis solution for extended periods of time, this can be detrimental to the sample. 2. Centrifuge at room temperature at 1500 rpm for 10 minutes. Remove the supernatant leaving behind the visible layer of white blood cells pellet. Then repeat step 1 until virtually all of the red blood cells are gone. Then vortex the pellet to spread the cells into the remaining drops of supernatant. 3. Add 3 ml of cell lysis solution to the centrifuge tube and right away pipette up and down to lyse the cells (make sure the solution is homogenous). 4. Add 6 l of RNase A (10 mg/ml) to the centrifuge tube. Mix the solution by inverting it several times and then incubate in a 37 oC water bath for 15 minutes. This can be run longer. 5. For protein precipitation, add 2 ml of protein precipitation solution (5 M ammonium acetate) to the centrifuge tube and then vortex until the solution look milky. 6. Centrifuge at 3000 rpm at 4 oC 15 minutes. The precipitated proteins will from a light brown pellet. If a protein pellet is not visible, repeat step 5. 7. Then pour the supernatant containing the DNA into a clean 50 ml Falcon tube containing 9 ml of isopropanol, do this at room temperature. 8. Mix the tube by inverting 25-30 times until white DNA pellet becomes visible (make sure all the pellet becomes visible). 9. Centrifuge at 3000 rpm at 4 oC 15 minutes. The DNA should be visible as a small white pellet. 10. Pour the supernatant and add 10 ml of 70 % ethanol. Invert several times to wash the DNA. 11. Spin again and pour off the 70 % ethanol. Then left the DNA air dry. Use a cotton swab to remove the excess supernatant on the sides of the tube. 12. Rehydrate the DNA in 1-1.5 ml of TE. Placed in 37 oC water bath for 2 hours to get the DNA in solution. Make sure that it is a homogenous solution. 13. Store at 20 oC. Additional Lecture : Topic : Clinical Application of Molecular Biology Laboratory Objective : to broden students horizon on the existing facilities of our molecular biology laboratory. Date and Place : Wednesday,11th December 2013 Class room Content : - Application of molecular biology technique in infectious diseases - Application of molecular biology technique in Forensic

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~ SELF ASSESSMENT ~

The Structure of the Plasma Membrane & The Transport Mechanism of Various Substances 1. Describe structure and function of phospholipids membrane; which molecule can diffuse across the membrane without mediated by protein (channel or carrier protein)? 2. Describe the structure of protein membrane and function of each protein in transport mechanism and its example! 3. Explain the difference of content and composition between intracellular and extracellular fluids! 4. Describe the passive transport mechanism through cell membrane! 5. Explain various substances which transported through passive process! 6. Describe factors that determine diffusion process! 7. Explain transport mechanism for molecule that soluble in lipid! 8. Describe sodium channel mechanism! 9. What is voltage gating channel? 10. Explain the difference between primary and secondary transportation with its examples! 11. What is co-transport?

Organelles & Inclusions Comprehend the structure of the organelles that involve in drug and alkohol detoxication !

Cytoskeletons 1. Mention three types of cytoskeleton! 2. Mentions minimal 1 examples and its function of each type in cytoskeleton! 3.

Identify the structures labeled of an axoneme and explain the role of each cytoplasmic component in the generation of axoneme movement.

Cell Organization in Connective Tissue 1. Explain about cells that synthesize elastic fiber! 2. Explain and give examples of dense regular collagenous connective tissue! 3. Describe characteristic of loose connective tissue!

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4. Describe cells in connective tissue that function as Antigen Presenting Cells and phagocytosis! 5. Describe ground substances that function as agent barrier! 6. Explain the consequences of severe vitamin C deficiency in connective tissue! 7. Explain the histologic structure of mucoid tissue!

1. 2. 3. 4. 5.

Cell Organization in Epithelial Tissue Describe three major type of cell junction and its function! Describe the function of epithelial tissue! Mention and give example every kind of epithelium! Describe the structure and function of basal lamina! Differentiate about cell polarity!

Nucleus & Chromosomes 1. Describe all of the protein that found at nucleoplasm! 2. Describe the definition and function of nucleoplasmic ring and nuclear basket! 3. Describe the nucleosome! Mention the proteins that arranged them! 4. Describe chromatin assembly factor! 5. Describe the function of nuclear pores! 6. Describe the X-machvation (lionization)! 7. Describe the differences between chromosome 1 and 2! 8. Describe the differences between chromosome X and Y! 9. Describe monosomy and trisomy! 10. Describe poliploidi, aneuploidi!

1. 2. 3. 4.

Introduction to Molecular Biology Describe about replication mechanism, and enzymes that are involved! Describe how to detect mutation in the gene. Describe about mutation, and its clinical implication Describe about DNA repair system!

Gene Expression 1. In When considering the initiation of transcription one often finds consensus sequences located in the region of the DNA where RNA polymerase(s) bind. Which are common consensus A. CAAT B. TATA C. TTTTAAAA D. both B and C E. both A and B 2. Which of the following occurs when RNA polymerase attaches to the promoter DNA? A. elongation of the growing RNA molecule B. initiation of a new polypeptide chain C. initiation of a new RNA molecule D. termination of the RNA molecule E. addition of nucleotides to the DNA template 3. When examining the genetic code it is apparent that A. there can be more than one amino acid for a particular codon.

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Study Guide The Cell as Biochemical Machinery

B. C. D. E.

AUG is a terminating codon there can be more than one codon for a particular amino acid the code is ambiguous in that the same codon can code for two or more amino acids there are 44 stop codons because there are only 20 amino acids.

4. A short segment of an mRNA molecule is shown below. The polypeptide it codes for is also shown: 5-AUGGUGCUGAAG : methionine-valine-leucine-lysine

Assume that a mutation in the DNA occurs so that the fourth base (counting from the 5 end) of the messenger RNA now reads A rather than G. What sequence of amino acids will the mRNA now code for? A. methionine-valine-leucine-lysine B. methionine-lysine-leucine-lysine C. methionine-leucine-leucine-lysine D. methionine-valine-methionine-lysine E. methionine-methionine-leucine-lysine 5. Which of the following takes place during translation? A. the conversion of genetic information from DNA nucleotides into RNA nucleotides B. conversion of genetic information from the language of proteins to the language of enzymes C. the conversion of genetic information from the language of nucleic acids to the language of proteins D. DNA replication E. the addition of nucleotides to a DNA template 6. During the process of translation, which translation site on the ribosome is filled by the iniatortRNA molecule A. A B. B C. P D. O E. E 7. Which of the following statements is true regarding gene expression? A. The 3' end of mRNA corresponds to the carboxyl terminus of the protein B. The first step is the association of mRNA with an intact ribosome C. Involves proof-reading of the mRNA D. Prokaryotic RNA usually undergoes nuclear processing E. Polypeptides are synthesized by addition of amino acids to the amino terminus 8. Which of the following best describes the relationship between genes and proteins A. one gene: one enzyme B. one gene: two polypeptides C. one gene: one polypeptide D. one gene: one protein E. none of the above describe the relationship 9. To describe the genetic code as degenerate indicates that A. mRNA is rapidly degraded B. The code is not universal among organisms C. Some amino acids have more than one codon D. Frameshift mutations are tolerated E. Stop codons may have corresponding tRNA molecules 10. A peptide has the sequence NH2-phe-pro-lys-gly-phe-pro-COOH. What is the sequence in DNA that codes for this peptide? A. 3' UUU-CCC-AAA-GGG-UUU-CCC B. 3' AUG-AAA-GGG-TTT-CCC-AAA-GGG
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C. 3' AAA-GGG-TTT-CCC-AAA-GGG D. 5' GGG-AAA-TTT-AAA-CCC-ACT-GGG E. 5' ACT-TAC-CAT-AAA-CAT-TAC-UGA

1. 2. 3.

Basic Feature of Enzyme Explain about co-enzyme and apo enzyme Differentiate about protein and non protein catalyst Explain about production and function of CK, LDH, ALT, and AST! Signal Transduction Explain the character of ligand/signaling molecules! Explain structure and function of each receptor type! Describe various second messengers forming process! Describe about phosphorylation protein kinase in the cytoplasm! Describe cell signaling mechanism until gene expression occurs! Describe the mechanism of action of drugs-receptors until biologys responses occur!

1. 2. 3. 4. 5. 6.

Cell Cycle 1. Cell cycle consists of several phases. Describe the events that occur during every phase! 2. Describe the type of cell division and its differences! 3. Describe the phases in mitosis and the events that occur during every phases!

Bioenergetics and Oxidative Metabolism 1. Which one of the following is the correct sequence of stages in cellular respiration? A. glycolysis, oxidative phosphorylation, and the citric acid cycle B. glycolysis, the citric acid cycle, and oxidative phosphorylation C. the citric acid cycle, oxidative phosphorylation, and glycolysis

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D. oxidative phosphorylation, the citric acid cycle, and glycolysis E. oxidative phosphorylation, glycolysis, and the citric acid cycle 2. Complex II differs from the other three complexes of the electron transport chain in one major aspect. What is this aspect? A. It is not located on the inner membrane of the mitochondria B. It does not require cofactors C. It does not pump protons D. It requires ATP for its reaction. E. It contains no covalently-bound FAD 3. During oxidative phosphorylation, the proton motive force that is generated by electron transport is used to: A. create a pore in the inner mitochondrial membrane. B. generate the substrates (ADP and Pi) for the ATP synthase. C. induce a conformational change in the ATP synthase. D. oxidize NADH to NAD+. E. reduce O2to H2O. 4. Almost all of the oxygen (O2) one consumes in breathing is converted to: A. acetyl-CoA. B. carbon dioxide (CO2). C. carbon monoxide and then to carbon dioxide. D. none of the above. E. water. 5. Cyanide, oligomycin, and 2,4-dinitrophenol (DNP) are inhibitors of mitochondrial aerobic phosphorylation. Which of the following statements correctly describes the mode of action of the three inhibitors? A. Cyanide and 2,4-dinitrophenol inhibit the respiratory chain, and oligomycin inhibits the synthesis of ATP. B. Cyanide inhibits the respiratory chain, whereas oligomycin and 2,4-dinitrophenol inhibit the synthesis of ATP. C. Cyanide, oligomycin, and 2,4-dinitrophenol compete with O2 for cytochrome oxidase (Complex IV). D. Oligomycin and cyanide inhibit synthesis of ATP; 2,4-dinitrophenol inhibits the respiratory chain. E. Oligomycin inhibits the respiratory chain, whereas cyanide and 2,4-dinitrophenol prevent the synthesis of ATP. 6. During chemiosmosis A. a concentration gradient is generated when large numbers of H+ ions are passively transported from the matrix of the mitochondrion to the mitochondrion's intermembrane space. B. energy is generated by coupling exergonic reactions with other exergonic reactions. C. ATP is synthesized when H+ ions move through a protein port provided by ATP synthase. D. H+ ions serve as the final electron acceptor. E. energy is released as H+ ions move freely across mitochondrial membranes

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7. A drug is tested in the laboratory and is found to create holes in both mitochondrial membranes. Scientists suspect that the drug will be harmful to human cells because it will inhibit A. glycolysis. B. the citric acid cycle. C. oxidative phosphorylation. D. Beta oxidation of fatty acids E. Oxidation of piruvate 8. Rotenone is a poison commonly added to insecticides. Insects exposed to rotenone will die because A. high levels of fermentation products will build up. B. water will not be produced and dehydration will occur. C. anaerobic respiration can't occur. D. of inadequate ATP production. E. None of the choices are correct. 9. Uncoupling of mitochondrial oxidative phosphorylation: A. allows continued mitochondrial ATP formation, but halts O2 consumption. B. halts all mitochondrial metabolism. C. halts mitochondrial ATP formation, but allows continued O2 consumption. D. slows down the citric acid cycle. E. slows the conversion of glucose to pyruvate by glycolysis. 10. Antimycin A blocks electron transfer between cytochromes b and c1. If intact mitochondria were incubated with antimycin A, excess NADH, and an adequate supply of O2, which of the following would be found in the oxidized state? A. Coenzyme Q B. Cytochrome a3 C. Cytochrome b D. Cytochrome e E. Cytochrome f

Cellular Responses to Injury and Death 1. Explain adaptations of cellular growth and differentiation 2. List the causes of cell injury 3. Explain the mechanisms of cells injury 4. Explain clinico-pathologic correlations with some examples of cell injury and necrosis 5. Explain the mechanisms of necrosis 6. Describe the morphology of necrosis 7. Explain the mechanisms of apoptosis 8. Describe the morphology of apoptosis 9. List some condition with pathologic calcification 10. Explain the mechanisms of senescence 11. Describe the morphology of cellular aging

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Cellular Intervention/Therapies 1. A 55-year-old woman with heart failure is to be treated with a diuretic drug. Drug X and Y have the same mechanism of diuretic action. Drug X in a dose of 5 mg produces the same magnitude of diuresis as 500 mg of drug Y. This suggests that : a. Drug Y is less efficacious than drug X b. Drug X is about 100 times more potent than drug Y c. Toxicity of drug X is less than that of drug Y d. Drug X is a safer drug than drug Y e. Drug X will have a shorter duration of action than drug Y because less of drug X is present for a given effect 2. In the absence of other drugs, pindolol causes an increase in heart rate by activating beta adrenoceptors. In the presence of highly effective beta stimulants, however, pindolol causes a dose-dependent, reversible decrease in heart rate. Therefore, pindolol should be classified as: a. An irreversible antagonist b. A physiologic antagonist c. A chemical antagonist d. A partial agonist e. A spare receptor agonist 3. Which of the following provides information about the largest response a drug can produce, regardless of dose? a. Drug potency b. Maximal efficacy c. Mechanism of receptor action d. Therapeutic index e. Therapeutic window

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~ CURRICULUM MAP ~
Smstr 10 9 8
Medical Emergency (3 weeks) BCS (1 weeks) The Respiratory System and Disorders (4 weeks) BCS (1 weeks) Elective Study II (1 weeks) 5 BCS (1 weeks) Alimentary & hepatobiliary systems & disorders (4 Weeks) BCS (1 weeks) BCS (1 weeks) The Endocrine System, Metabolism and Disorders (4 weeks) BCS (1 weeks) BCS (1 weeks) Clinical Nutrition and Disorders (2 weeks) BCS (1 weeks) Special Topic : - Palliative medicine -Compleme ntary & Alternative Medicine - Forensic (3 weeks) Elective Study II (1 weeks) Special Topic: -Travel medicine (2 weeks)

Program or curriculum blocks Senior Clerkship Senior Clerkship Senior clerkship


Elective Study III (6 weeks) Clinic Orientation (Clerkship) (6 weeks)

The Cardiovascular System and Disorders (4 weeks)

The Urinary System and Disorders (3 weeks)

The Reproductive System and Disorders (3 weeks)

Musculoskeletal system & connective tissue disorders (4 weeks) BCS (1 weeks) Hematologic system & disorders & clinical oncology (4 weeks) BCS (1 weeks) Medical Professionalism (2 weeks) BCS (1 weeks) Studium Generale and Humaniora (3 weeks)

Neuroscience and neurological disorders (4 weeks) BCS (1 weeks) Immune system & disorders (2 weeks)

Behavior Change and disorders (4 weeks)

The Visual system & disorders (2 weeks) BCS (1 weeks) The skin & hearing system & disorders (3 weeks)

BCS(1 weeks) Infection & infectious diseases (5 weeks)

BCS(1 weeks) Evidence-based Medical Practice (2 weeks)

BCS (1 weeks) Health Systembased Practice (3 weeks) BCS (1 weeks) The cell as biochemical machinery (3 weeks) BCS(1 weeks)

BCS(1 weeks) Community-based practice (4 weeks) -

Special Topic - Ergonomi - Geriatri (2 weeks)

Elective Study I (2 weeks)

Medical communication (3 weeks)

Growth & development (4 weeks) BCS: (1 weeks)

BCS (1 weeks)

Pendidikan Pancasila & Kewarganegaraan (3 weeks)

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~ REFERENCES ~ Used in the Block The Cell as Biochemical Machinery Student Standard References: 1. Gartner LP, Hiatt JL : Concise Histology, Philadelphia, W.B. Saunders, 2011, pp 873(H2) 2. Guyton AC, Hall JE : A Textbook of Medical Physiology, 11th ed., 2006, pp.1-51; 829901 (PS1) 3. Baynes, J.W. and Dominiczak, M.H. Medical Biochemistry second edition.Elsevier London. 2005:p. 641 (B ) 4. Robbins SL, Kumar V : Basic Pathology, London, Saunders, 7th ed, 2003, pp.3-31 (BP) 5. Strachan T & Read AP; Human Molecular Genetics, John Wiley & Sons (Asia) PTELTD (HMG) 6. Trevor AJ, Katzung BG, and MastersSB :Pharmacology Examination & Broad Review, 7th ed, 2005, pp. 10-19 (PH) 7. Goodman SR : Medical Cell Biology, 2nd ed, pp. 195-202 (CB) 8. Gene Therapy and Genetic Counseling Additional recommended reading: 9. Fawcett DW, Jensh RP : Bloom & Fawcetts Concise Histology, 2nd ed, London, Arnold, 2002, pp 1- 27(H1) 10. Ganong, WF: Review of Medical Physiology, 20thed, New York, Lange Medical Books/McGraw-Hill, 2001, pp 1-48 (PS2) 11. Murray RK, Granner DK, Mayes PA : Harper, s Illustrated Biochemistry,26th ed, New York, Lange Medical Books / McGraw-Hill, 2003 , 314 373; 74-102 (B2) 12. Alberts B, Johnson A, Lewis J : Molecular Biology of THE CELL, 4TH ed , New York, Garland Science, 2002, pp 1010 1021 (MB2)

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Paper Assessment Form Block The Cell as Biochemical Machinery

Name : ........................................... Student Reg. Number : ........................................... Facilitator : ........................................... Title : ........................................... Supervisors (Facilitator) scoring with 60% qualification :] No 1. 2. 3 4 Item Assessment Ability to find the literature Communication/Attitude Quality of material Students interest and motivation TOTAL Range Score (%) 0-20 0-30 0-40 0-10 100 Score

Supervisor,

(...........................................) NIP. Paper Assessment Form Block The Cell as Biochemical Machinery

Name : ........................................... Student Reg. Number : ........................................... Facilitator : ........................................... Title : ........................................... Supervisors (Facilitator) scoring with 60% qualification : No 1. 2. 3 4 Item Assessment Ability to find the literature Communication/Attitude Quality of material Students interest and motivation TOTAL Range Score (%) 0-20 0-30 0-40 0-10 100 Score

Supervisor,

(...........................................) NIP.
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TIME TABLE REVISION :

1. Lecture 7. Introduction to Molecular Biology : 15 November 2011 2. Lecture 8. Gene expression : 17 November 2011

3. Practicum microscopic structure of connective tissue : 18 November 2011 4. Student project presentation yang tanggal 15 November pindah ke tanggal 18 November 2011

TIME TABLE REVISION :

1. Lecture 7. Introduction to Molecular Biology : 15 November 2011 2. Lecture 8. Gene expression : 17 November 2011

3. Practicum microscopic structure of connective tissue : 18 November 2011 4. Student project presentation yang tanggal 15 November pindah ke tanggal 18 November 2011

TIME TABLE REVISION :

1. Lecture 7. Introduction to Molecular Biology : 15 November 2011 2. Lecture 8. Gene expression : 17 November 2011

3. Practicum microscopic structure of connective tissue : 18 November 2011 4. Student project presentation yang tanggal 15 November pindah ke tanggal 18 November 2011

TIME TABLE REVISION :

1. Lecture 7. Introduction to Molecular Biology : 15 November 2011 2. Lecture 8. Gene expression : 17 November 2011

3. Practicum microscopic structure of connective tissue : 18 November 2011 4. Student project presentation yang tanggal 15 November pindah ke tanggal 18 November 2011

UdayanaUniversity Faculty of Medicine, MEU

53

Study Guide The Cell as Biochemical Machinery

Paper Assessment Form Block The Cell as Biochemical Machinery

Name : ........................................... Student Reg. Number : ........................................... Facilitator : ........................................... Title : ........................................... Evaluatorsscoring (presentation) with 40% qualification : No Item Assessment 1. Quality of material 2. Capability of information searching 3 Critical thinking TOTAL Evaluator, (................................................) NIP. Range Score (%) 0-60 0-10 0-30 100 Score

Paper Assessment Form Block The Cell as Biochemical Machinery

Name : ........................................... Student Reg. Number : ........................................... Facilitator : ........................................... Title : ........................................... Evaluatorsscoring (presentation) with 40% qualification : No Item Assessment 1. Quality of material 2. Capability of information searching 3 Critical thinking TOTAL Evaluator, (................................................) NIP. Range Score (%) 0-60 0-10 0-30 100 Score

UdayanaUniversity Faculty of Medicine, MEU

54

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