Syllabus

Course Meeting Times

Lectures: 1 session / week, 2 hours / session

Prerequisites

7.03 Genetics

7.05 General Biochemistry

7.06 Cell Biology

or

7.28 Molecular Biology

Course Description

The molecular biology revolution firmly established the role of DNA as the primary carrier of genetic information and proteins as the primary effector molecules of the cell. The intermediate between DNA and proteins is RNA, which initially was regarded as the "molecule in the middle" of the central dogma. This view has been transformed over the past two decades, as RNA has become recognized as a critical regulator of cellular processes.

In this course, we will investigate the diverse types and functions of different RNA species, with a focus on "non-coding RNAs," i.e. those that do not directly encode proteins. The course will convey both the exciting discoveries in and frontiers of RNA research that are propelling our understanding of cell biology as well as the intellectual and experimental approaches responsible.

To achieve these goals, we will first discuss studies of long-described classes of RNAs, such as ribosomal RNA and catalytic RNA, and then debate more controversial findings concerning less-characterized classes of RNAs, such as circular RNA and long non-coding RNA. After reading about the Nobel Prize winning discovery of small interfering RNA (RNAi), we will visit a local RNA therapeutics company that has translated this discovery into a novel class of disease treatments. We will consider new aspects of gene regulation revealed through the discovery of microRNAs and debate whether microRNAs should be considered to be simply endogenous small interfering RNAs. We also will investigate very current topics, such as RNAs that function in the CRISPR / Cas9 host defense systems. In this system, a guide RNA directs the Cas9 enzyme to cut DNA at a specific place, leading to the exciting potential for CRISPR / Cas9 approaches to gene therapy in the clinic and novel experimental approaches in the laboratory.

Throughout the course, we will learn about the techniques employed in the discovery of various classes of RNAs, ranging from traditional genetic and biochemical approaches to the more recent application of next generation DNA and RNA sequencing approaches. Class sessions will be highly interactive and will focus on critical discussion of the primary research literature. Our broad goal will be to equip students with the tools to read and critique cutting-edge primary research articles, design properly controlled experiments to answer a given biological question, and understand how basic scientific discoveries are translated into novel therapies for disease.

Format

This course meets for two-hour sessions once a week. Unlike lecture-based classes, this course focuses on reading, understanding, and critiquing primary research publications. Two publications will be assigned per class, and students are expected to read both papers before attending each class. Through interactive discussions, students will be taught how to design properly controlled experiments to address a particular research question, interpret results, and draw valid conclusions based on the data. Students are required to attend every class and actively contribute to the discussions. No previous knowledge of the subject matter is required, as all relevant background information for each assigned publication will be provided.

Course Objectives

The main objective for this course is to open up a world of groundbreaking scientific discoveries to students by teaching them how to critically read and evaluate the primary scientific literature. This goal will be accomplished through studying the types and functions of RNA molecules within the cell. Upon successful completion of the course, students will be able to:

  • Locate and read primary research articles on topics of scientific interest.
  • Explain common cell biology laboratory methods.
  • Design experiments to answer a given biological question, including proper controls.
  • Appreciate the historical progression of the RNA field, including current state-of-the-art research topics.
  • Understand how basic scientific discoveries are translated into novel disease therapies.

To aid in accomplishing these objectives, students will be required to complete one written assignment and one oral assignment as described in the Assignments section.

Grading

This course will be graded pass/fail based on attendance, preparedness, participation in class discussions, and completion of the written assignment and oral presentation.

Calendar

WEEK # TOPICS KEY DATES
1 Introduction and Course Overview  
2 The discovery of miRNAs as gene regulators  
3 Roles for miRNAs beyond gene downregulation  
4 From siRNA discovery to therapeutic agent  
5 Circular RNAs and the competing endogenous RNA hypothesis  
6 Role of lncRNAs in X chromosome inactivation  
7 Regulation of genomic imprinting by long non-coding RNAs Written Assignment due
8 Field trip to Alnylam Field trip to the Alnylam Pharmaceuticals, Inc.
9 Catalytic functions of RNA and the RNA-world hypothesis: Ribozymes  
10 It's all about the ribosome  
11 Chemical modifications of mature RNA molecules  
12 Harnessing an RNA-guided immune system to treat human disease  
13 Oral Presentations and Course Evaluations Oral Presentations due