Course Meeting Times
Lectures: 1 session / week, 2 hours / session
There are no absolute prerequisites, but some knowledge of genetics, biochemistry, and molecular biology is helpful. Ideally, candidates will have successfully taken at least one of the following classes:
7.05 General Biochemistry
Chemistry, Chemical Engineering, and Bioengineering students are also highly encouraged to attend even without any of the above prerequisites. Interested students uncertain if their academic coursework is sufficient for this seminar should contact the instructors.
The natural world is a mega-factory of small molecules, peptides, fatty acids, phospholipids, and a host of other compounds. These compounds, or natural products (NPs), are immensely diverse in structure and function. The intricate chemical architectures of NPs arise from a fascinating interplay of simple starting materials and biosynthetic enzymes to create the varied structures that enable a wide array of biological functions. Indeed, NPs have strongly influenced how we treat infectious disease, cancer, pain, and a host of other conditions. Roughly half of the drugs that have been approved in the past 30 years are NPs, derivatives of NPs or NP-inspired.
Where do these NPs come from? What organisms produce these NPs and for what reasons? How are these compounds biosynthesized? Can we discover new compounds or modify the structure and function of existing compounds to inspire new therapeutics? Decades of work to answer these questions have yielded immense progress. Furthermore, the explosion of genomic data over the past 15 years has revolutionized NP research and allowed researchers to explore the wealth of NPs using novel, high-throughput approaches.
In this discussion-based course, we will delve into research on discovering NPs from producing organisms, investigating the biochemistry of NP production, and using synthetic biology to create NP derivatives—all with a particular emphasis on how genomic data guides and informs all these studies. Our class will primarily focus on bacterial producers of two types of NPs: ribosomally synthesized and post-translationally modified peptides (RiPPs) and non-ribosomal peptide–polyketide (NRP–PKS) hybrids, drawing on papers from laboratories in chemistry, chemical engineering, biological engineering, and biology. We will conclude with a discussion of NPs produced by plants and NPs of the human microbiome.
Students will hone their skills reading and critiquing primary research articles and become familiar with common chemical and biological techniques used by NP researchers. This class will also provide students with the opportunity to examine a NP paper of their choice and develop their critical writing and speaking skills through a short written assignment and oral presentation to the class. In addition, students will have the opportunity to engage with a career panel of scientists and professionals with experience in NP research.
For each week of the course, students will be assigned two articles to read. A brief introduction to the papers will be provided the week before they are assigned. Students should read the papers critically before each class and come prepared to discuss the following questions:
- What was the main goal of the paper?
- Why was this goal important?
- What experiments were performed to explore this area? What question(s) did each experiment seek to answer? How well did the experiment answer the question(s)?
- Explain the methodology used in these experiments.
- What figure or table presents THE most important experiment, and what was/were THE key control experiment(s)?
- What are the main conclusions of the paper? Are alternative conclusions plausible? How might these alternatives be tested?
- What other methods could have been used to answer the questions? How might findings from such experiments alter the conclusions?
- What are the questions raised from the results and the next experiments that could be performed to address those questions?
- To learn to read and critically appraise the merits of articles in the primary scientific literature.
- To understand current methodology underlying natural product research.
- To improve discussion, writing and presentation skills.
Grading and Requirements
The course will be graded as “pass” or “fail.” A student who attends each session, actively participates in the discussions, and completes both assignments in a satisfactory manner will receive a passing grade.
|week #||topics||key dates|
|1||Introduction to the Course|
|2||RiPPs (ribosomally synthesized and post-translationally modified peptides): Discovery via Culture/Manipulation of the Native Producer|
|3||RiPPs: Discovery via Genomics/Data-Driven Strategies|
|4||RiPPs: Biosynthesis and Enzyme Function/Mechanism|
|6||Panel Discussion with Natural Product Professionals|
|7||NRPs (non-ribosomal peptide NPs): Discovery via Genomics/Data-Driven Strategies||Written assignment due|
|8||NRPs: Biosynthesis and Enzyme Function/Mechanism|
|11||Culture-Dependent and Metagenomic Methods of NP Discovery from Complex Environments|
|12||Applications of NPs in Combating Diseases|
|13||Student Presentations and Evaluation||Oral presentation due|