BIO 3121 MOLECULAR BIOLOGY

FALL 2009

Christopher T. Cole
University of Minnesota - Morris

SYLLABUS

Workload Expectations
How Do You Succeed?
Assistance Available
Outline
Text
Topic Schedule
Work Schedule
Grading

LabReports
Students with Disabilities
Classroom Conduct
Academic Integrity
Sexual Harassment
Use of Class Notes for Commercial Purposes

Other Web Sites

Figures from Lectures

Figures are large image files used in lecture, so they will be slow to download. They are in the same order as the course outline. Click on the link to get the list, which is near the bottom of this page. The links connect to the Powerpoint files used in class (you will need Microsoft Powerpoint to view them). Here is a link to the powerpoint viewer (the link is so long you will probably have to copy it piecemeal into a browser): http://www.microsoft.com/downloads/details.aspx?FamilyID=428d5727-43ab-4f24-90b7-a94784af71a4&DisplayLang=en

"1-Minute Essays": Archive of questions and answers from past classes

Archive is organized in the same order as the course outline. This is a basic text file, no figures, etc., since the original answers were distributed by e-mail. Some topics change from year-to-year, so if there are questions about something that is not included this year (e.g. requirements for a term paper, regulation of lambda), don't panic.

 

SYLLABUS

Instructor: Christopher T. Cole
Office: 2080 Science Bldg. Lab: 2060 Science Bldg.
Lecture: T Th 10:00 - 11:40 in Science 1020; Lab sections meet 2-5:00 T, 1-4:00 W (plus arranged times) in Science 2170.


Contacting me:
Phone: 589-6319 e-mail: colect@morris.umn.edu Fax 320-589-6371
Phone: 589-6319 e-mail: colect@morris.umn.edu Fax 320-589-6371
– If you really want to get a message to me, use the telephone and call me at the office phone number.
– The daily flood of e-mail has become so huge that your message can easily get buried or lost. Student messages are my top e-mail priority (even before my boss), BUT I may not even see it. If you want a response, use the phone.
– Unsigned e-mail will not receive a reply.

Prerequisites for this course include Cell Biology and Organic Chemistry. Genetics is recommended but not required if you have taken Bio 1111; Biochemistry is also useful background. Consequently I assume that you are familiar with some introductory-level material; if any of this is foggy, you should review your notes and text from the cell bio book, at least.

Course content summary: As indicated in the Outline, the format of this course is to examine first the materials & methods commonly used in molecular biology, then the "central dogma" (DNA makes RNA makes protein) in some detail, then look at how that process is regulated in prokaryotes, and then look at how that process is modified in eukaryotes. In lecture and lab, this includes an introduction to the fundamental techniques for producing recombinant DNA, analyzing DNA variation, and looking at examples of how these techniques contribute to our understanding of molecular evolution and, by extension, to the analysis of other areas of biology as well. The content is summarized further in the “Course Outline” and “Topic Schedule” below.

The other principal focus of the course is on developing your skills for doing science. These are not just technical skills (how to use a pipettor reliably, how to set up a PCR reaction) but more broadly applicable skills: how to plan, conduct, complete, and report a body of work. This constitutes a major portion of the course material.

Course Goals: Throughout the course I emphasize the empirical basis for our understanding of how things work. In fact, I would even say that this course is more about the design and interpretation of experiments than it is about molecular biology per se! Consequently, the analysis (and design) of experiments is not limited to labs but forms a core of lectures, group activities, problem sets, and exams. For this reason also, we begin the course with a survey of many of the techniques that are now basic skills not only for molecular biologists but for biologists in general-- even those whose primary interests are in evolution, ecology and behavior!

The complexity of molecular-scale phenomena produces a rich technical vocabulary which is an essential tool for understanding– a necessary means to the end of explaining molecular biology.

These goals unite the lecture and laboratory portions of the course. You will be expected to understand not only how the principal methods of molecular biology work, but how they are used to inform us about the structures and functions of molecules far too small to be visualized directly. This combined capacity for visualization of molecular interactions and interpretation of empirical evidence forms the core of the course. You will not only read about the work of molecular biologists, but also report your own molecular biology work.

Reporting biological research work is another central goal of this course. If you ignore the texts by Pechenik or Knisely (see below), your work will suffer and you won’t like the consequences. Lab projects take several weeks, and the lab reports (papers, poster, oral) comprise a major portion of the lab work and of your grade. This teamwork– both conducting and reporting work– is a central skill for working biologists, and is emphasized more in this course than in other courses you are familiar with.


Workload Expectations

Bio 3121 is a 5 credit course; consequently it requires about 25% more work than the other biology courses you have taken.

Sometimes students take courses with the idea that they are interested in the big picture, the general principles, and are not going to bother with the details. If you have similar intentions you are welcome to audit the course but my intentions and expectations for enrolled students are different and you are likely to be frustrated.

I expect at least two hours of study for each hour of class. This matches university credit hour policy for the level of effort to achieve an average grade in the course. How you work is at least as important as how much you work. Moreover it will be important that you do not fall behind. Over the years, the most important factor determining how well students do in this course is how well they keep up with the course– work on a daily basis is best.

University of Minnesota Senate Policy on Academic Credit Hours:

One semester credit is normally to represent, for the average University of Minnesota undergraduate student, three hours of academic work per week (including lectures, laboratories, recitations, field work, and study) averaged over the term in order to complete the work of the course. It is expected that the academic work required of graduate and professional students will exceed three hours per credit per week. Professional norms and the nature of course activity (e.g., clinical experiences, some laboratory work, and some studio activities) may require more than three hours of work per week per credit hour, with college approval and appropriate notification to the students. These “workload” expectations relate only to completion of the course work; greater effort is likely required to earn high grades.


How do you succeed as a student?

First, re-read "Workload Expectations", above.

A question that came in on a "One Minute Essay" once was "What is the easiest way to keep everything straight?". Here are my answers.

1. Organize. Review the structure of the course. Note the outline. This is the key to what the main points are at different times during the course.

2. Recall this strategy: material is presented as general principles and specific examples. Make sure you can summarize the general principles and provide a specific example for each. Conversely, know what principle is exemplified by each example. (Examples: What are the general patterns we see, or "strategy", of gene regulation in prokaryotes? What general features of molecular evolution are illustrated in the globin genes?)

3. Know the vocabulary. This is key to clear thinking, and hence to understanding the material-- as well as to being able to communicate that understanding. Molecular biology has a lot of specialized vocab.

4. Make your study active-- don't just read the material. Study should include drawing and writing. Especially, you should make up your own questions.

How do you succeed as a scientist?

"You've got to try and be with people who are brighter than yourself."

"You've got to be prepared sometimes to do some things that people say you're not qualified to do."

"Since you know you're going to get into trouble, you ought to have someone to save you after you're in deep shit. So you better always have someone who believes in you."

- James D. Watson March, 1993

Assistance Available

Just ask. Besides the rich store of material available online, I am always eager to help you understand the course material; if I am not able to meet with you when you stop by, we will schedule a time when we can meet. If desired, we can also schedule review/help sessions with class T.A.’s (students who have taken the course in the past and done well). Sometimes another perspective can help clarify information.

Outline

The overall organization of the course is:

1. MATERIALS & METHODS
2. THE CENTRAL DOGMA

             Prokaryotic Replication & Repair, Transcription, and Translation
3. REGULATION OF GENE EXPRESSION
4. EUKARYOTES & "THE C-VALUE PARADOX"
             Regulation
             mRNA processing
             Duplication and "Hyperdrive": beyond the central dogma
             Immune system rearrangements
             Transposons, Viruses, and Cancer

Text

REQUIRED:
1) Weaver, R.F. 2007. Molecular Biology, 4th ed. WCB McGraw-Hill. The 3rd edition of this text is just as good for this course, and the 2nd would also work; see the note below.


2) Knisely, K. 2005. A Student Handbook for Writing in Biology. Sinauer.
OR
Pechenik, J.A. A Short Guide to Writing About Biology. Addison Wesley Longman. This book will also be used for Bio Comm I
Any edition of either of these books (Knisely or Pechenik) will be fine. I somewhat prefer the earlier versions as they are more succinct.

Recommended:
Strunk, W., Jr., and E.B. White. 2000. The Elements of Style. 4th ed. Allyn & Bacon, Boston, MA. Earlier editions of this book are also suitable. You should have this book handy if you have any assignments, in any class or job, that require writing

Wikipedia – LOTS of good info available, including links to animations.

Weaver’s text emphasizes the empirical basis for our understanding of molecular biology, making it a good partner for our course. However, the sequence of topics is somewhat different than our course, so we will adjust the reading accordingly (see Topic Schedule). Some students are bothered by "jumping around" in the text, while others are not. To help with this, I have provided detailed reading assignments (below). I hope you find that the strengths of the text (e.g. summaries of the main points for each section, explanations of experimental methods, and interpretations of experimental results) outweigh any drawbacks.


For example, we begin our course with a survey of the Materials & Methods used in molecular biology, and Weaver's text presents a good summary of many of these, but that summary is split into chapters 2-5, so we will draw on the appropriate portions of those chapters, augmented by reading material on reserve in the library.


Students have used the first or second editions, but here’s the comment of one student who used the second edition and studied with others using the third: “I found that unlike other authors, Weaver actually had a reason to put out a 3rd ed. There are a lot of important ‘updates’ to the book. I think it would be beneficial to announce this at the beginning of the semester to warn us that there are significant differences between the texts.” You may also find chapters of a biochemistry text, such as those by Lehninger or Stryer, to have useful summaries of the main points, though they usually ignore the experimental evidence behind the stories.

The guides to writing in biology will be important for your lab reports. ‘Nuff said.

Topic Schedule

The Schedule of Topics below is approximate. Weaver's text (2007, 4th edition) is abbreviated as W4, followed by chapter, section, or page numbers. Readings for the 2nd and 3rd editions (W2, W3) are listed below that. Though not included here, you should ALSO READ THE CHAPTER SUMMARIES."Reserve" materials available at Briggs Library and on e-reserve.

Week Topic Reading (W4)
Part I Introduction, Materials & Methods  
1-3 Materials & Methods Reserve (Alberts et al. or Karp Ch 18 -- more info later); W4 xxi-xxii, 27-29, 51-73, 83-104, 106, 230-233 (Box 9.1), 771, 798-800
Part II The Central Dogma  
4 DNA Structure 12-27
  Replication & Repair Ch 20: semiconservative 640-641, semidiscontinuous 642-644, priming & bidirectional 644-647; Enzymology 650-654; strand separation 655-660; DNA damage & repair: 660-668, mismatch repair 672-673.
5 Transcription 38-41, 116-118, Ch 6 thru 139, 162-168 (first column)
6 Translation & Genetic Code 42-46; 521-530; 564-574, 589-593, 599-604, 607-614,
624-630.
Part III Regulation: Prokaryote Models  
7-8 The Prokaryotic Perspective  
  Operons Ch 7 through 195; 240-241; TRAP handout; lac operon
handouts
Part IV Eukaryotes: Regulation, Hyperdrive & the C-Value Paradox  
9 The Eukaryotic Context Reporter Gene Transcription 113-114, sec 5.6 through DNAse footprinting (p. 118); Histones: 13.1 & 13.2 (pp 359-368);
Capping: 444-449; Polyadenylation 450-456
10 Eukaryotic gene regulation RNA pols 250-253; Promoters 266 (col. 2)- 277 (col.1)
  Introns & splicing Intro 399-403; Spliceosomes & Snurps 406(col. 2)-
407; Alternative Splicing 455-459; Ch 16 501-504 ff on RNAi and miRNA; tRNA splicing handout
11 C-Value & Gene Families Genome sizes 28-29
12 Transposons 743-751
  Immune system 751-756
13 Viruses Retrotransposons etc. 756-761
14 Cancer: Eukaryotic regulation gone awry Reserve (Karp 1999 Ch. 16)

Corresponding reading assignments from the 2nd and 3rd edition of Weaver's text:

Week Topic Reading (W2) Reading (W3)
Part I Introduction, Materials & Methods    
1-3 Materials & Methods Reserve (Alberts et al.); also 34,60-79,92-111,115-116,112-126,234-237,798-800 Reserve (Alberts et al.); also xvi-xvii, 32-35, 58-78,90-111,114-115,244-247 (Box 9.1), 805-806, 830-832
Part II The Central Dogma    
4 DNA Structure 17-30 17-31
  Replication & Repair Ch20 Ch 20: semiconservative 666-668, semi-discontinuous668-671, bidirectional 672-675; Enzymology 677-679; three DNA polymerases in E. coli 685-688. DNA damage & repair: alkylation 692, UV 693, direct repair 694-695, excision repair in prokaryotes 695-696, mismatch repair 701.
5 Transcription Ch 6 thru148, 165-172 44-48, 124-125, Ch 6 thru 147, 171-175 first column
6 Translation & Genetic Code 49-54,428-544, 567-578, 594-599, 606-625, 626-630
48-53; 545-555, 585-595, 613-618, 625-627, 630-639, 649-656
Part III Regulation: Prokaryote Models    
7-8 The Prokaryotic Perspective    
  Operons Ch 7, 244-246 (sec. 9.2), 254-257 Ch 7; 256-257, 264-267
Part IV Eukaryotes: Regulation, Hyperdrive & the C-Value Paradox    
9 The Eukaryotic Context 5.6, 380-390, 462-473, 476-478 Reporter Gene Transcription 119-122, sec. 5.6 thru DNAse footprinting (p. 125); Histones: 13.1 & 13.2 (pp. 385-395); Capping: 470-477; Polyadenylation 477-484
10 Eukaryotic gene regulation 261-266, 279-283, 288-289, 291-292 RNA pols 271-274; Promoters 287-295 (col. 1)
  Introns & splicing 418-422, 428-430, 448-450, 450-454, 456-457 Intro 424-428; Spliceosomes & Snurps 432-433; Alternative splicing 455-459; tRNA splicing 464-465
11 C-Value & Gene Families 34 Genome sizes 33-35
12 Transposons 753-761 774-782
  Immune system 761-764 782-787
13 Viruses 767-773; Reserve Retrotransposons etc. 787-796
14 Cancer: Eukaryotic regulation gone awry Reserve Reserve (Karp 1999 Ch. 16)

 

Work Schedule

Tentative: One aim, incompletely accomplished, is to prevent piling up work at the end of the quarter.

Week #
Element Due
1  
2  
3  
4 Graded Problem Set #1
5 Exam #1
6  
7  
8 Lab Report #1
9 Graded Problem Set #2
10  
11 Exam #2
12 Lab Report #2
13  
14 Graded Problem Set #3
15 Lab Report #3 (Poster & Oral)
16 Exam #3 ("Final") 11-1:00 16 Dec Sci 1020

Problem sets and exams will cover lecture, text and lab material. Ungraded problem sets get used as group problems in class, as well as for your own review. These will be distributed periodically, serving as preparation for exams. Three problem sets, due during weeks 4, 9, and 14, will be graded.

The Lab Manual includes a detailed schedule for lab exercises.


Grading

                                      "Chance favors the prepared mind."
                                                                        - Louis Pasteur

Bio 3121 is a 5-credit course. In other words, the general expectation is that it will require roughly 25% more work than other biology lab courses!

The grading scheme comes from suggestions from students in the past, and I welcome your recommendations for changes (this year or in the future).

Item
Points
Labs: flow charts (labs 2-9; 2 @ 10)
20
Team Lab Reports (3; more detail
in the section on Labs)
     Report Scores
100
     Peer Scores:3@20
60
Graded Problem Sets (3 @ 20)
60
Exams (3 @ 100)
300
Total
530


Letter grades will be based on percent of the total possible: A = 92% or better, B = 82-88%, C = 72 - 78%, D = 50 - 68%, N = 50 % or less. “+” or “-“ extensions get added based on where scores fall between these grades, whether grades show improvement during the term, peer evaluations, etc. For example, if you have a 92% at the end of the quarter, you will get an A; if you have an 89.2%, you might get an A- or a B+.


Here is the University of Minnesota policy on grading standards (definition of grades):


A: Represents achievement that is outstanding relative to the level necessary to meet course requirements.

B: Represents achievement that is significantly above the level necessary to meet course requirements.
C: Represents achievement that meets the course requirements in every respect.
D: Represents achievement that is worthy of credit even though it fails to meet fully the course requirements.
S: Represents achievement that is satisfactory, which is equivalent to a C- or better.
F (or N): Represents failure (or no credit) and signifies that the work was either (1) completed but at a level of achievement that is not worthy of credit, or (2) was not completed and there was no agreement between the instructor and the student that the student would be awarded an I (see also “I” below).
I (Incomplete): Assigned at the discretion of the instructor when, due to extraordinary circumstances, e.g. hospitalization, a student is prevented from completing the work of the course on time. Requires a written agreement between the instructor and student.


Make-up exam policy: “Make-up” quizzes and exams are available only when a student has a good reason for missing the regular test and arrangements have been made before the missed test (or, in the event of calamity immediately preceding the test, as quickly as possible afterwards).


Lab Reports


Be sure to read the detailed information in the Lab Manual!! Lab reports for this course take the format of primary research articles (2) and a poster for a professional conference (1). You will not want to be surprised at the level of rigor expected for these reports, as they comprise about 30% of the grade.

Students with disabilities


It is my practice as well as University policy to provide reasonable accommodations to students with disabilities. Course materials are available in alternative formats to people with disabilities upon request. Please contact the Disability Services office, 589-6163, Room 362 Briggs Library, to discuss accommodation needs. Here are two comments regarding services available:

The University of Minnesota is committed to providing all students equal access to learning opportunities. Disability Services is the campus office that works with students who have disabilities to provide and/or arrange reasonable accommodations. Students registered with Disability Services who have a letter requesting accommodations, are encouraged to contact the instructor early in the semester. Students who have, or think they may have, a disability (e.g. psychiatric, attentional, learning, vision, hearing, physical, or systemic), are invited to contact Disability Services for a confidential discussion at 320-589-6163, or call Colleen Frey at freyc@morris.umn.edu. Additional information is available at the DS web site at www.morris.umn.edu/services/dsoaac/dso.

As a student you may experience a range of issues that can cause barriers to learning, such as strained relationships, increased anxiety, alcohol/drug problems, feeling down, difficulty concentrating and/or lack of motivation. These mental health concerns or stressful events may lead to diminished academic performance or reduce your ability to participate in daily activities. University of Minnesota services are available to assist you with addressing these and other concerns you may be experiencing. You can learn more about the broad range of confidential mental health services available on campus via www.mentalhealth.umn.edu.

Classroom Conduct


A classroom is a forum founded on respect and courtesy among all participants; individuals who are not willing to conduct themselves accordingly will be dismissed; those whose behavior violates the University Student Conduct Code will be subject to disciplinary action.


Audio recording equipment is allowed provided that you let me know that you will be using it. Cell phones and hats should both be off in the classroom.

Academic Integrity


Lab reports are team projects, and your score will be based on my evaluation of your report and the scores you receive from your teammates evaluating your contributions. Exams are designed to evaluate your knowledge and abilities as an individual; you may use (and I encourage) any collaboration with others in preparation for tests, but absolutely no assistance from others during the test. The UMM Biology program has a strong tradition of academic integrity (I have never had a problem with this on biology exams at UMM), and any infringement on this would be grounds for immediate dismissal from and failure in the course.

Plagiarism of any sort or source will result in penalties that may range from no credit on the report or test to failing the course.

This has happened. Though rarely a problem in the past, students have been dismayed to find that this rule is real.


University Statement:

Scholastic dishonesty means plagiarizing; cheating on assignments or examinations; engaging in unauthorized collaboration on academic work; taking, acquiring, or using test materials without faculty permission; submitting false or incomplete records of academic achievement; acting alone or in cooperation with another to falsify records or to obtain dishonestly grades, honors, awards, or professional endorsement; altering forging, or misusing a University academic record; or fabricating or falsifying data, research procedures, or data analysis. In this course, a student responsible for scholastic dishonesty can be assigned a penalty up to and including an "F" or "N" for the course. If you have any questions regarding the expectations for a specific assignment or exam, ask.

These descriptions of plagiarism are taken from Pechenik (2004: A Short Guide to Writing about Biology; the emphasis is in the original): “Submitting anyone else’s work under your own name is plagiarism, even if you alter some words. Presenting someone else’s ideas as your own is also plagiarism.... Plagiarism is theft. It is one of the most serious offenses that can be committed in academia, where original thought is the major product of one’s work – often months, sometimes years of physical and mental work.” Pechenik follows this with suggestions of how to take notes that will prevent unintentional plagiarism.

Sexual Harassment


University policy prohibits sexual harassment as defined by the University of Minnesota Regents' policy: http://134.84.237.31/PDF%20Pages/SexHarassment.pdf

Use of Class Notes for Commercial Purposes

University Policy on Use of Class Notes for Commercial Purposes:

Materials presented in class represent the intellectual effort of the instructor and should be protected to assure the accuracy of any public representations of those materials. Class notes taken or class materials collected by students cannot be distributed for commercial purposes without instructor permission. For enforcement purposes, instructors are encouraged to include in their syllabi a statement notifying students of this policy.


Use of Electronic Equipment in the Classroom

You are welcome to make audio recordings of lectures, provided that you ask permission before doing so– you don’t have to ask every day, just once is fine. Do not make video recordings. Computers can be used for taking notes during class, but please do not use them for checking e-mail, browsing web sites, etc. as this can be distracting to other students. As stated above, cell phones should be turned off during class. Any use of a cell phone during an exam is grounds for immediate dismissal from the exam, with no credit allowed for the exam.

Further Information
You can find further University-wide information on the following topics at this website:
/www.policy.umn.edu/Policies/Education/Education/SYLLABUSREQUIREMENTS.html


1. Grade definitions from the Administrative Policy: Grading and Transcripts: Twin Cities, Morris, Rochester.
2. Scholastic Dishonesty (see Board of Regents Policy: Student Conduct Code and the Administrative Policy: Teaching and Learning: Instructor and Unit Responsibilities: Twin Cities, Morris, Rochester).
3. Administrative Policy: Makeup Work for Legitimate Absences: Twin Cities, Morris, Rochester
4. Administrative Policy: Use of Personal Electronic Devices in the Classroom: Twin Cities, Morris, Rochester
5. Administrative Policy: Appropriate Student Use of Class Notes and Course Materials: Twin Cities, Morris, Rochester
6. Board of Regents Policy: Student Conduct Code; Administrative Policy: Teaching and Learning: Student Responsibilities (Twin Cities, Morris, Rochester)
7. Board of Regents Policy: Sexual Harassment
8. Board of Regents Policy: Diversity, Equal Employment Opportunity, and Affirmative Action
9. Statement about the availability of mental health services

 

Other Web Sites

Here is a very good online Molecular Biology book, simple, with intersting links:

http://www.web-books.com/MoBio/

http://vector.cshl.org
Cold Spring Harbor is a major leader in molecular genetic research, and this website presents an "Almanac" of basic information, especially illustrating basic techniques. It also has a good collection of links.

http://dp.portlandpress.co.uk/glick/search.htm
This is an online glossary for molecular biology and biochemistry, with over 3,000 terms.

Websites for Microchips and Microarrays:

www.unil.ch/ibpv/microarrays.htm
Information about making microarrays.

ihome.cuhk.edu.hk/~b400559/array.html
Background info on gene chips, links to products for making and scanning microarrays, databases of gene expression results, reviews of software, troubleshooting info.

www.gene-chips.com/
Links to information about microarray technology, including companies working on them.

A couple of good articles:

Hegde, P. et al. 2000. A concise guide to cDNA microarray analysis. BioTechniques 29:548-562.

Jain, KK. Biochips for gene spotting. Science 294:621-625. Note that this article is followed by an advertising section devoted to background info and advertisements for gene chips, analysis hardware and software, etc.

Figures from Lectures

These are links to the sets of Powerpoint slides used in lectures.

I. Introduction

II. Materials & Methods

A. Enzymes, Cloning, & Genetic Engineering

B. Microbiology, Electron microscopy, X-ray diffraction, Centrifugation, Chromatography, Electrophoresis

C. Labels, Transfers, Probing, Chips

D. Sequencing, Synthesis

E. PCR and beyond

II. The Central Dogma

A. Replication and Repair

B. Transcription

C. Translation

III. Gene Regulation

A. Operons 1

B. Operons 2

Cartoon of ara operon in action

Cartoon of trp operon in action

IV. Eukaryotes

A & B. Eukaryotes A&B

C. Eukaryotes C

D. Eukaryotes D

E. Eukaryotes E

F. Eukaryotes F

G & H. Eukaryotes G & H: Transposons & Antibodies

I. Eukaryotes I: Viruses

J. Eukaryotes J: Cancer