Course Description
Course Goals
Course Organization
Journal Club
Problem Sets
Student Assessment
Hints for Success

Online Molecular Biology/Genetics textbooks: NCBI Bookshelf
Alberts et al., Molecular Biology of the Cell (2002)
Darnell et al., Molecular Cell Biology (2000)
Griffiths et al., Modern Genetic Analysis (1999)
Genomes 2 (2002)

Course Description

Molecular Biology is the study of how life works at the level of molecules. Molecular biologists study the molecular mechanisms underlying the most conserved biological processes; how DNA is replicated, how genes are transcribed, and how proteins are synthesized. But the most central question in this subdiscipline has been the question of how cells regulate the expression of the genes. In unicellular organisms, genes are activated or repressed in response to environmental cues; nutritional signals, stress signals or mating signals. In multicellular organisms, genes are also regulated in response to environmental cues but in this case, the environment is usually other cells. In multicellular organisms, the most important function of gene regulation is the creation of different specialized cells types from initially identical cells during embryonic development, a process critical to the reconstruction of the multicellular organism in each generation. It is the molecular mechanisms underlying the control of gene expression that will form the essential content of this Molecular Biology course.

This course will explore four central principles that I want you will understand in a deep way by the end of the course.
1. Genes are regulated by sequence-specific DNA binding proteins that regulate the initiation of transcription. We want to understand the molecular mechanism by which transcription factors recognize and bind regulatory DNA and how this regulates mRNA synthesis.
2. Transcriptional control is combinatorial, with different combinations of activator and repressor proteins acting sometimes over long distances to control the initiation of transcription. Combinatorial control is accomplished through DNA sequences that bind gene regulatory proteins and function like integrating circuits to sum multiple inputs. These sequences are sometimes called genetic switches. We want to understand how genetic switches work.
3. Increasingly we find that chormatin structure and epigenetic mechanisms play an important role in gene expression and human disease. We will explore what is known about epigenetic modulation of gene expression.
4. In eukaryotic cells, gene expression is often regulated at the post-transcriptional level. We will explore specific examples of post-transcriptional regulation of gene expression-including alternative RNA splicing, RNA stability, mRNA translation and post-translational protein modification and degradation.

Molecular Biology 311/312 is built upon a foundation of Introductory Biology (Bio 151 and Bio 200) and Chemistry (Chem 110/120) and is designed to prepare you for other upper division courses or graduate work in Biochemistry, Cell Biology, Neurobiology, Developmental Biology and Immunology. These subdisciplines of biology together form the foundation of modern medicine, and thus an understanding of Molecular Biology is crucial for continued study in these areas. This course will also enhance your understanding of Physiology, possibly Ecology, and certainly Evolution and Phylobiology. The pre-requisites for this course are in place to ensure that you are prepared to be successful in this course. Specifically, from Genetics 151, I will expect that you are familiar with complementation testing and what it tells you, with the genetic code, with mutations (nonsense and missense, dominant and recessive) and the basics of DNA replication. From Biology 200, I expect that you will be familar with basic protein and DNA structure, enzyme structure, function and regulation, free energy and thermodynamics, and the basics of PCR, gene cloning, transcription, splicing and translation. From Chemistry, I will expect that you are familiar with the basis of noncovalent interactions (hydrophobic, ionic, hydrogen , and van der Waals), pH, molar concentrations, reaction rate constants and equilibria, binding affinity, and radioisotopes.
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Arguably, the most important thing I teach is critical thinking. The content of molecular biology you could teach yourself, but how to question ideas, how to critically analyze data and how to design experiments, this is a skill set that is harder to acquire. I have designed this course to help you work on these skills. The problem sets, the primary literature, and more informal discussion in lecture will all provide you with an oppotunity to practice. In my experience, everyone leaves this course better able to do these things than when they started, and from what we hear from alumni, these are skills you will find useful in your life after college. I have four specific goals for this course.
(1) To give you an advanced understanding of genes and how they are regulated. This content will be provided through assigned readings in your textbook, assigned schlolarly reviews, web sites, lectures, powerpoint slides, and discussions. Completion of this course should provide you with a sophisticated understanding of the central principles of molecular biology.
(2) To mentor you in how to read the primary scientific literature. In 10 years, much of the current content of this course will superceded by new ideas, as new research modifies the scientific landscape. In a field that changes as rapidly as this one does, you need to know how to learn on your own. In science, this means knowing how to read the primary scientific literature. In this course, I will step you through this process, starting with some classic papers and progressing into the current literature.
(3) This course should develop your critical thinking skills. Scientists make their living by critically evaluating data on a daily basis. I will help you develop your critical thinking skills by asking you to analyze your own data in lab, and by asking you to independently analyze data presented in primary literature articles. We will especially work on two kinds of scientific thinking; genetic inference, and on what kinds of evidence can be used to support causality and molecular mechanism.
(4) This course should expand your problem solving skills. Scientists ask questions and solve problems. While not all of you will become scientists, many of you will do work that requires you to solve problems that do not have already known solutions. This will require you to apply concepts learned in one context to a new situation. Problem solving requires logic, organization, and synthesis, and it is a skill, like any other, that improves with practice. I will mentor you in this skill by giving you problems as homework, by asking you to pose questions and experiments in class, and I will evaluate this skill on exams.

Summary of Goals:

1. To provide a solid foundation in the existing concepts of molecular biology.
2. To teach you how to read the primary scientific literature.
3. To develop your critical thinking skills.
4. To expand your problem solving skills.

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The lecture material is divided into four main sections. In the first section we will review and develop your understanding of the structure of genes and proteins and about how genes replicate, mutate, are repaired, and evolve. In the second section we will begin our study of gene regulation in earnest, starting with simple genetic switches that work in prokaryotic cells. We will use the lac operon of E. coli as our model system because it is one of the best studied molecular models for how proteins control gene expression, and because the lac operon demonstrates how a genetic switch works at the molecular level. Once you understand how the lac genes are regulated, we are in a position to explore the more complex solutions to gene regulation that have evolved in eukaryotic cells and multicellular organisms. In this third section of the course, we will look in detail at the regulation of transcription in eukaryotes and compare it to how transcription is regulated in prokaryotic cells. Finally, in the fourth section, we will examine some uniquely eukaryotic post-transcriptional mechanisms for regulating gene expression; at the regulation of splicing, of mRNA transport, RNAi, translational control and regulated protein stability.
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Journal Club

Several of the goals of this course are served by introducing you to the primary literature. Reading these journal articles exposes you to the process of scientific investigation. By reading these papers, you should gain insight into how scientists design experiments to answer questions, and into the way scientists analyze genetic and biochemical data to draw conclusions. By reading the variety of primary articles I have chosen for you, I hope you will develop an appreciation for elegant experimental design, rigorous analysis of data, and creative scientific model building . In class we will try to address the following questions: What is a well-controlled experiment? What kinds of evidence are required to infer cause and effect between two phenomena. What does it mean to over-interpret the data?

Reading the primary literature will likely feel quite challenging in the beginning compared to reading the predigested material of a textbook. To help show you how to do this, we will go over the first paper as a whole group, and I will serve as the discussion leader. After the first paper, student groups will lead the journal club discussions. You can choose which paper you want to work on, and then your group of 4-5 will be responsible for leading the discussion of your paper. To lead your discussion, you will need to be conversant with the background for your paper, and be able to explain the molecular techniques used in the experiments. You can find information on techniques in your textbook, and often online. To understand the background. you often must read at least some of the papers referenced in the introduction section of your paper. To help you prepare to lead your discussion, you should schedule a meeting with me as a group at least 5 days prior to your journal club. To prepare for that meeting, you need to have read your paper carefully and done as much background research as possible. My role will be to direct you to other sources if you are stuck. You must come well prepared to this meeting or it will be a waste of your time and mine.

I will also provide a list of questions for all of you to direct your reading of the assigned paper. You should work on these questions in small groups (no more than 3 people per group) to prepare for class. Each person must turn in at least 4 JC homework sets; you are allow one missed assignment, and on the day you are part of the leader group, you do not need to turn in question answers. You should plan to read through the paper at least once on your own though before you meet with your study group to answer the questions (or if you prefer to work alone, you may). You should expect to spend at least 3 hours preparing for journal club. You should take notes on your paper in your class notebook, and you should jot down comments in the margins of your xerox copy of the paper; label the lanes in the figure, note questions. In class time we will discuss the paper together, ironing out the issues that you had difficulty with in your groups. I will both ask for volunteers and call on individuals to explain portions of the paper. From experience, I know that you will find that these papers become easier to read as the semester progresses and that you will find yourself a more independent learner as a consequence of developing this skill.

Your contribution to Journal Club (JC) will be evaluated in two ways. If you are not in the group leading the discussion, you will need to hand in the answers to the assigned questions about the paper the day of the discussion. Please make a xerox copy of your answers so you can turn one copy in at the beginning of class and use the other copy during the discussion. If you are leading the discussion, you will be individually evaluated on your comprehension of the experimental work in the paper. Specifically, you will be evaluated on your ability to effectively explain to your classmates what question was addressed in the experiment, how the experiment was done and what the data show.
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Problem Sets

Another tool I use to help you develop your critical thinking and problem solving skills is to assign periodic problem sets. These will be due at the beginning of class on the day shown in the course schedule. I will pass these out in class, or post on the WEB one week before they are due. You may work on these problems on your own or with one other person. The names of all persons contributing to the solution of the problem must appear on the problem set when you turn it in. You must turn in at least 5 of the 6 assignments to receive the 50 point problem-set credit towards your final grade in the course. The problem answers will be posted online or on the bulletin board outside my office. It is your responsibility to check your answers and come see me in office hours if you do not understand the posted solutions (encouraging you to be an independent learner :)).
Your motivation to do these problems sets will consist of the following three incentives. You will learn the course material better and more deeply by solving these problems, and hence perform better on the exams. Problems like these will appear on Biology 311 exams and on GREs and MCATs. You will get to know other students in the class by working with them on these intellectual puzzles.
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Student Assessment

Midterm I	100 Pts
Midterm II	100 Pts
Final Exam	200 Pts
Problem sets (5 of 6)	50 Pts
Assigned Journal Club questions (4 of 6)	40 pts
Journal Club Discussion	30 Pts
Total:	520 pts

Grading Scale

The grading scale will be as follows:

90-100%	A
86-90%	A-
82-85%	B+
77-82%	B
73-77%	B-
69-73%	C+
64-69%	C
60-64%	C-
50-60%	D

A problem that can be encountered with "non-curved" grades is that the instructor can misjudge and write an exam that is too difficult. This almost never happends to me after as many years of experience as I have. Nonetheless, if I write an exam on which no one can get above 90%, I will adjust the scores for that exam upward so that the top score is 90%.

College Grading Policy: (from the Lewis & Clark College Catalog)
A: Outstanding work that goes beyond analysis of course material to synthesize concepts in a valid and/or novel or creative way.
B: Very good to excellent work that analyzes material explored in class and is a reasonable attempt to synthesize material.
C: Adequate work that satisfies the assignment, a limited analysis of material explored in class.
D: Passing work that is minimally adequate, raising serious concern about readiness to continue in the field.
F: Failing work that is clearly inadequate, unworthy of credit.

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Hints for Success

Time management:
How much time should you expect to commit to this class? Molecular Biology 311/312 is a 6 credit course. Since most college courses are 4 credit courses, you should expect this course to require more work than your other courses, one-third more work, to be precise. I estimate it will require a minimum of 2 hours/credit hour (12 hours per week) outside class time to pass this course, and about 18 hours per week (3 hours/credit hour) to get an A. Most students take Molecular with 2 other 4-5 credit academic courses and a PE or activity course for a 15-16 hour semester. If you have 22 credits this semester, you should think about whether this is a good decision for you and if there are alternatives.

That said, I have also tried very hard to plan this course in such a way as to spread the work out-so that it does not come all at once, or just before exams. There will usually be either a problem set or a journal club article to read each week, except for exam weeks. Either of these assignments should take you about 3-5 hours to prepare. The textbook reading should take you about 3 hours per week, and reviewing your lecture notes, revising them, and coming to see me in office hours another 2-3 hours per week (see below). Your lab work should take a maximum of 8 hours per week outside class time. If you are spending more time than this, please come see me right away so we can look for ways to help you study more efficiently.

Active learning:
Research in cognitive psychology suggests that the more actively we engage with new material, the better we learn it. What does active learning mean? It means doing something yourself-working with the material intellectually-solving problems, designing experiments, asking questions. What can you do to make your learning more active in lecture?

• Read the textbook reading assignment before lecture-it will help you to follow along and help you take better notes. For each section assigned in the textbook, write down the major concept you learned by reading it. Use the CD-ROM animations; these often let you participate in some way, a trick to help your learning be more active.
• Take lecture notes, and review them shortly after class to fill in details you didn't have time to write down.Use the powerpoint slides as a tool for reviewing your notes. In class, focus your note taking on the big questions, the central concepts. Use the lecture outline to help you identify what those ideas are, and to follow the structure of the lecture.
• Ask questions: in class, in lab, in office hours, in the hall, by email. Actively engage in the learning process. It is both my duty and my pleasure to assist your learning, and your questions are the best tool I have for personalizing your education to your learning needs.
• Form a small study group of 2-3 students. Meet regularly to discuss the homework, the lecture, to review for exams. Having to explain a concept to someone else is very good practice for having to explain it to me on an exam; it forces you to articulate your ideas and to notice what concepts are still a bit confusing to you.
• Use office hours on a regular weekly basis. I have 4 hours each week set aside just to answer your questions, and your lab intructor has additional hours set aside to discuss lab questions with you. You are wasting your money if you are not taking advantage of this resource. Since I will be writing the exams, I am your best source of accurate information.

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