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Syllabus MCDB 3135 (2012F) - MCD Biology

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<strong><strong>MCD</strong>B</strong> <strong>3135</strong> – Molecular Cell <strong>Biology</strong> I<br />

Fall 2012 <strong>Syllabus</strong><br />

Professor: Greg Odorizzi, odorizzi@colorado.edu, 303-735-0179<br />

Office hours: Tuesday 12:00 – 2:00 PM, Room A420C <strong>MCD</strong> <strong>Biology</strong>, or by appointment<br />

Lab Coordinator: Joy Power, Joy.Power@colorado.edu, 303-735-2723<br />

Teaching Assistants: Kati Buchtel, Christine Crotzer, Roni Denglar, Eli Gendron, April Griffin<br />

Course web site: learn.colorado.edu<br />

Lecture hours: Tuesdays & Thursdays, 9:30 – 10:45 AM in HUMN 1B50<br />

Important dates:<br />

Wednesday, September 12 (5:00 PM): deadline to drop the course without penalty<br />

Thursday, September 20, 2011: Midterm Exam I (9:30 – 10:45 AM in HUMN 1B50)<br />

Wednesday, October 10 (5:00 PM): deadline to drop the course without petitioning the dean<br />

Thursday, October 18, 2011: Midterm Exam II (9:30 – 10:45 AM in HUMN 1B50)<br />

Thursday, November 15, 2011: Midterm Exam III (9:30 – 10:45 AM in HUMN 1B50)<br />

Monday, December 17, 2011: Final Exam (7:30 – 10:00 PM in HUMN 1B50)<br />

Course requisites: <strong><strong>MCD</strong>B</strong> 2150 or EBIO 2070 (prerequisite); CHEM 1133 (pre-requisite or corequisite);<br />

<strong><strong>MCD</strong>B</strong> 3140 is recommended with either <strong><strong>MCD</strong>B</strong> <strong>3135</strong> or <strong><strong>MCD</strong>B</strong> 3145.<br />

Course description: examines the central dogma of biology by discussing DNA, RNA, and<br />

protein, and how their synthesis (DNA replication, transcription, RNA processing, and translation)<br />

is regulated. Incorporated into the discussion is how recombinant DNA techniques are used to<br />

discover and dissect cellular processes, how to design and interpret experiments, and<br />

understanding the limits of experiments to draw conclusions. These principles are the foundation<br />

for subsequent examination of intracellular mechanisms in <strong><strong>MCD</strong>B</strong> 3145.<br />

Learning objectives: After taking this class, you should know the key concepts of the central<br />

dogma of molecular biology, including the composition of genomes and the basic mechanisms of<br />

replication, transcription, RNA processing, translation and RNA turnover, and how the complexes<br />

that perform these activities identify their targets, carry out their function and can be regulated to<br />

meet cellular needs. In addition, you should have a basic understanding of the experimental<br />

approaches and deductions that have shaped, and continues to shape, our understanding of these<br />

concepts. Doing well in this class requires solid prior understanding of genetics, biochemistry<br />

and organic chemistry. For more details about the learning objectives, see the ‘Learning Goals’<br />

below.


<strong><strong>MCD</strong>B</strong> <strong>3135</strong> – Molecular Cell <strong>Biology</strong> I! Fall 2012 <strong>Syllabus</strong><br />

COURSE STRUCTURE<br />

Textbook: The recommended textbook for this course is Molecular <strong>Biology</strong> by Cox et al., 1 st<br />

edition (2012), Freeman Publishing, ISBN-13: 978-0-7167-7998-8. Copies of this text are on<br />

reserve at Norlin library.<br />

Lectures: The lectures will follow the general order of the central dogma of biology<br />

(DNA→RNA→Protein). We will, therefore, first discuss the composition and structure of DNA,<br />

the composition of genomes, the use of recombinant DNA in research, DNA replication and<br />

repair, transcription, RNA processing, mRNA translation, and regulation of gene expression. Key<br />

experiments and deductions that underlie the understanding of the different processes will be<br />

discussed.<br />

A pdf of the lecture slides will be provided on the course website preceding each lecture. The<br />

slides comprise a skeletal record of what happens in the lecture. However, you may find the<br />

lecture slides unintelligible without your own written notes. Therefore, do not think of them as a<br />

second, independent “book” you can read but instead as a collaborative record of the lecture that<br />

you will create.<br />

Clickers: To obtain extra credit, you will need an i-clicker (not a different system such as H-ITT<br />

or PRS). See http://oit.colorado.edu/cuclickers-faq/general-questions/where-can-iclicker-remotesbe-purchased.<br />

Clickers will be used for rapid feedback to foster interactive learning in a large<br />

classroom setting. Clicker questions will be used during class to make you think about and<br />

discuss with your peers how the newly discussed material fit within the bigger picture of<br />

molecular biology and how experimental observation and experimental design can address<br />

questions in molecular biology. Register your i-clicker ASAP.<br />

COURSE SCHEDULE:<br />

Dates Topic Text<br />

Aug 28 – Sep 18 Genes & Genomes Chapters 6-10<br />

Sep 20 Midterm Exam I<br />

Sep 25 – Oct 16 DNA Replication and Repair Chapter 11-14<br />

Oct 18 Midterm Exam II<br />

Oct 23 – Nov 13 Transcription and Translation Chapter 15-18<br />

Nov 15 Midterm Exam III<br />

Nov 27 – Dec 13 Regulation of Gene Expression Chapter 19-22<br />

Dec 17 Final Exam<br />

2


<strong><strong>MCD</strong>B</strong> <strong>3135</strong> – Molecular Cell <strong>Biology</strong> I! Fall 2012 <strong>Syllabus</strong><br />

EXAMS and GRADING<br />

Your grade in <strong><strong>MCD</strong>B</strong> <strong>3135</strong> will be derived from your final score calculated as follows:<br />

Midterm Exam I 22.5%<br />

Midterm Exam II 22.5%<br />

Midterm Exam III 22.5%<br />

Final Exam 22.5%<br />

Problem Sets 10%<br />

Total 100%<br />

Midterm Exams: Three midterm exams will be given during class time. Each exam will count<br />

toward your final grade. See the ‘Course Schedule’ for exam dates.<br />

Final Exam: The final exam will focus on the material discussed after Midterm Exam 3.<br />

Weekly Problem Sets: Weekly problem sets will be administered through the course web site; no<br />

new problem set assigned the week of an exam. Failure to complete a problem set will result in a<br />

zero for that set. The average of the ten highest problem set scores will count for 10% of your<br />

final grade. The lowest two problem set scores will be dropped.<br />

Exam policies:<br />

1. The Midterm and Final exams must be completed in ink. Using a pencil on any part of an<br />

exam will void the entire exam’s eligibility for a re-grade (see below).<br />

2. Pens and ID are the only personal items you may have with you during an exam. Any other<br />

items you bring (backpacks, phones turned OFF, etc.) must be placed entirely under your seat and<br />

are subject to being moved at the TAs' and professor's discretion.<br />

3. Requests to reconsider grading must be submitted in writing with your original exam to Joy<br />

Power within one week of the exam return date. Answering any part of an exam in pencil will<br />

void the entire exam’s eligibility for a re-grade. If anything on the exam submitted for regrading is<br />

found to be altered from its original state, it will be considered a breach of the honor code and<br />

will be grounds for failure in the course and additional disciplinary action.<br />

Extra credit: Extra credit will be based on clicker use (regardless of whether you get the answers<br />

right) and on input from Joy Power and TAs. To get credit for the whole semester, register your<br />

clicker at the beginning of the semester. The amount of extra credit awarded is at the discretion<br />

of the professor. Cheating with clickers by having someone other than yourself use your clicker<br />

during class is considered a breach of the honor code and will result in the loss of all clicker<br />

points for the semester for both yourself and the person bringing your clicker, as well as any<br />

additional disciplinary action as indicated by the honor code. Correct clicker use will be<br />

monitored by the professor and TAs during class.<br />

3


<strong><strong>MCD</strong>B</strong> <strong>3135</strong> – Molecular Cell <strong>Biology</strong> I! Fall 2012 <strong>Syllabus</strong><br />

CLASS POLICIES:<br />

Attendance: Attendance in class is optional but strongly encouraged.<br />

Etiquette: Please refrain from doing anything that might distract you or others (eating, reading<br />

newspapers, surfing the web, texting, and engaging in conversations). Please shut off cell<br />

phones. If you must leave class early, please exit with the least amount of disruption.<br />

Academic integrity: Cheating will not be tolerated and will be subjected to disciplinary action as<br />

discussed above under exams and clickers and as indicated by the honor code. All cheating will<br />

be reported to the University. Please review the University honor code: http://<br />

www.colorado.edu/policies/student-honor-code-policy. It is easier to pass this course by putting<br />

the energy into understanding the material rather than cheating.<br />

Letters of recommendation requirements: Acceptance into programs to further your education<br />

can be very competitive. Thus, you should carefully choose letter writers who know you well and<br />

who can honestly state that you achieved one of the top scores in their class and that your<br />

demonstrated enthusiasm, diligence, and hard work makes the writer confident that you will be<br />

an excellent candidate for the school of application. For me to write a letter of recommendation,<br />

you must have done very well in the class, and you must have been an active participant.<br />

Lecturer’s of smaller classes will usually know you much better, and their letters of<br />

recommendation will, therefore, usually carry much more weight.<br />

Disabilities: If you qualify for accommodations because of a disability, please submit to me a<br />

letter from Disability Services in a timely manner so that your needs may be addressed.<br />

Disability Services determines accommodations based on documented disabilities. Please see<br />

guidelines at: http://www.colorado.edu/disabilityservices/.<br />

Responsibilities: In a class of 200 or more students, it is impossible to teach directly to<br />

everyone’s needs. It is my (and the TAs) responsibility to come to class well prepared and to<br />

provide students with multiple pathways to learning the topics. It is your responsibility to make a<br />

significant effort by reading the text and coming to class prepared for the material.<br />

TIPS ON HOW TO DO WELL:<br />

The most important point is to keep up. The pace is unrelenting because the field of molecular<br />

biology is a rapidly expanding due to intense research. The following practices will help:<br />

1. Print out slides before each lecture.<br />

2. Take good notes during lectures.<br />

3. Actively participate in clicker questions.<br />

4. Read the textbook before and after class.<br />

Your grade will be decided entirely from your final score, not on how you do compared to other<br />

students, so it will never hurt you to help fellow students. In fact, research on learning has shown<br />

that whether you are on top of the material or are having a hard time understanding the concepts,<br />

you will improve your learning by discussing the material with other students. Memorizing slides<br />

and texts is not an efficient method of learning. While some memorization is required to become<br />

literate in molecular biology, the primary goal of the course, and what you will be tested on, is<br />

understanding the key concepts of molecular biology and how to interpret simple experimental<br />

observations.<br />

4


<strong><strong>MCD</strong>B</strong> <strong>3135</strong> – Molecular Cell <strong>Biology</strong> I! Fall 2012 <strong>Syllabus</strong><br />

LEARNING GOALS FOR <strong><strong>MCD</strong>B</strong> <strong>3135</strong>:<br />

After completing this course, students should be able to:<br />

1. Compare the structures of DNA and RNA.<br />

a) Describe how the building blocks of DNA and RNA are similar and how they are different.<br />

b) Describe the 3-D structure of DNA.<br />

c) Describe the nature of DNA supercoiling, its advantages/disadvantages, and how it is relieved.<br />

d) Describe denaturation and renaturation of double-stranded nucleic acids, methods to measure<br />

the degree of double-strandedness, and practical applications of these techniques.<br />

e) Describe how dideoxynucleotides are used to determine DNA sequences.<br />

f) Explain the difference between a gene and a genome.<br />

g) Describe the mechanistic basis for gene duplication and gene transposition and the role both<br />

have in evolution.<br />

2. Describe techniques for manipulating and characterizing cloned DNA.<br />

a) Describe the role of restriction endonucleases in gene cloning.<br />

b) Explain the procedures by which DNA fragments can be ligated into plasmid vectors,<br />

introduced into recipient cells, and their presence selected in the cell population.<br />

c) Describe the key elements required for a plasmid to be useful as a cloning vector.<br />

d) Describe how PCR works and how it can used to generate enough starting material for<br />

cloning.<br />

e) Describe how DNA sequencing works and its practical applications.<br />

f) Compare the procedures for making clone libraries from genomic DNA versus cDNA as<br />

starting material, and cite examples where each would be useful.<br />

g) Explain how to screen clones and/or entire libraries for a DNA segment of interest.<br />

h) Compare the methods for determining gene function in vitro and in vivo.<br />

i) Compare different types of cloning vectors in terms of their applications for cDNA versus<br />

genomic DNA cloning and for production of proteins.<br />

3. Explain the process of DNA replication.<br />

a) Interpret results of the experiments that distinguished proposed models of DNA replication.<br />

b) Explain the semidiscontinuous nature of DNA replication.<br />

c) Explain the utility of temperature-sensitive mutations in the study of DNA replication.<br />

d) Compare the events of replication on the leading and lagging strands (the trombone model).<br />

e) Explain the processivity of DNA polymerase III.<br />

f) Compare the events that occur at replication origins during the initiation of DNA synthesis in<br />

bacteria and eukaryotes.<br />

g) Describe the properties of a DNA molecule that allow it to serve as a template for replication.<br />

h) Describe the roles of DNA helicase, SSBs, the β clamp, DNA gyrase, and DNA ligase.<br />

i) Describe how termination of replication in bacteria differ.<br />

j) Explain the importance of telomeres with respect to germ cells and cancer.<br />

k) Describe the factors that contribute to the high fidelity of DNA replication.<br />

l) Contrast the events of nucleotide excision repair and base excision repair.<br />

m) Explain how parental and newly synthesized strands are distinguished in mismatch repair.<br />

5


<strong><strong>MCD</strong>B</strong> <strong>3135</strong> – Molecular Cell <strong>Biology</strong> I! Fall 2012 <strong>Syllabus</strong><br />

4. Describe the key steps in transcription and translation.<br />

a) Explain the role of a promoter in transcription.<br />

b) Describe the steps during initiation of transcription in bacteria versus eukaryotes.<br />

c) Explain the relationship between a pre-RNA and a mature RNA.<br />

d) Describe the differences in transcription of rRNAs, tRNAs, and mRNAs and explain their<br />

functional relationship.<br />

e) Diagram the structure of a typical eukaryotic gene, showing locations of the transcriptional<br />

start site, 5’-untranslated region (UTR), exons, introns, donor and acceptor splice sites,<br />

translational start site, translational stop site, 3’UTR, and poly-A addition sequence.<br />

f) Explain the steps in processing of an hnRNP into a mature mRNA, and describe the role of<br />

snRNAs and the spliceosome.<br />

g) Describe the triplet nature of the genetic code and how the identities of individual codons<br />

were established.<br />

h) Distinguish between synonymous and nonsynonymous mutations in the genetic code.<br />

i) Explain how tRNAs function as adaptor molecules.<br />

j) Compare the initiation of translation versus elongation.<br />

k) Explain how the effect of a nonsense mutation differs from that of a frameshift mutation.<br />

l) Explain how polysome formation differs in bacteria versus eukaryotes.<br />

m) Explain how bacterial translation is inhibited by certain antibiotics.<br />

5. Describe how gene expression is regulated.<br />

a) Describe the relationship between histones and and DNA in a nucleosome core particle.<br />

b) Explain how nucleosomes are organized into higher levels of chromatin.<br />

c) Describe the structural and functional difference between heterochromatin and euchromatin.<br />

d) Describe the histone code and explain how it determines the state of a chromatin region.<br />

e) Diagram a typical bacterial operon.<br />

f) Describe the mechanistic nature of inducible and repressible operons in bacteria.<br />

g) Describe the mechanistic function riboswitches.<br />

h) Explain the difference between a transcriptional activators and a transcriptional repressor;<br />

between a coactivator and a corepressor.<br />

i) Explain the difference between a general transcription factor and a gene-specific transcription<br />

factor.<br />

j) Describe how the domain structure of transcription factors relate to their function.<br />

k) Describe mechanisms by which transcription factors are converted between active and<br />

inactive forms.<br />

l) Explain the concept of epigenetics in the control of gene expression.<br />

m) Describe how alternative splicing can effectively increase the number of genes in the genome.<br />

n) Describe 3 different mechanisms of translational-level control of gene expression.<br />

o) Describe ways in which mRNA stability is maintained or destroyed.<br />

p) Describe how ubiquitination causes proteins to be unstable.<br />

6

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