Course Meeting Times
Lectures: 1 session / week, 2 hours / session
Prerequisites
Course Description
Over the course of millions of years, nature has been quietly at work to select highly efficient and specialized biomolecules that perform a vast myriad of tasks. Today, researchers can assume this historical role of nature. By precisely controlling aspects of the evolutionary process, we can develop similarly specialized and novel biomolecules that suit specific needs. Utilizing controllable systems and fine-tuning selection factors, biomolecules can be readily evolved to accelerate reactions, catalyze reactions with unconventional substrates, and bind new targets. Beginning with a population diversified with random mutations, evolution is achieved by iteratively increasing selection stringency to obtain individuals with desired traits. Being able to drive and direct evolution has revolutionized the way in which we develop biomolecules. Now utilized in many biotechnological applications, and recognized by the 2018 Nobel Prize for Chemistry, directed evolution is truly a staple in biomolecular design.
This course will cover the many ways in which we have realized evolution in the laboratory toward functional biomolecules, such as protein and nucleic acid-based therapeutics, enzymes that catalyze production of synthetic drugs, and carbon-dioxide capture molecules to lessen the impact of climate change. Students will both become familiar with the field of directed molecular evolution and learn how to critically analyze primary research papers, design research experiments and present data relating to molecular biology and evolution. The class will be entirely discussion based. Students will develop essential communication skills for careers in biological and biomedical sciences through a written assignment and an oral presentation. The importance of directed evolution in biomedical and biotechnological careers, both academic and industrial, will be highlighted. A breadth of opportunities to hone core scientific skills and explore the applied biological career space will be offered.
Format
The format for this course will be entirely discussion based with classes held over a flexible weekly 2-hour time slot. Each week will have a distinct theme within the context of directed evolution techniques and advances. Two primary research papers will be assigned for each week of the course, along with video or other instructive aids where applicable. A brief introduction to the papers will be provided the week before they are assigned along with a description of a relevant topic that the paper exemplifies. Students are expected to thoroughly read the main papers provided and to be prepared to discuss each of the figures and tables. Students should read these papers critically, focusing on experimental design and controls, before each class and come prepared to discuss the following questions:
- What is the central hypothesis or aims of the authors? What are the research goals of the authors, and what is the broader applicability of this research?
- What are the key experiments performed, and how do they test the authors’ hypotheses?
- Are the data from these experiments presented in a clear way? Is it straightforward to understand? How might the data have been presented more clearly?
- Do the data/results from these experiments support the conclusions of the authors or inferences they make from the experiments?
- What other experiments might be performed, or controls used, to improve the experiment or alternatively test the hypothesis?
Intended Learning Outcomes
Our anticipated learning outcomes for you during the course will primarily focus on learning to read and critically evaluate primary research articles from the scientific literature. At the end of this course you should be able to:
- Comfortably search scientific literature databases.
- Read, comprehend, and critically evaluate primary research papers.
- Understand the principles of experimental design and thinking.
- Demonstrate an understanding of the principles of directed evolution and techniques used to evolve biomolecules in a laboratory setting.
- Peer-review a scientific article.
- Comfortably present data from a primary research article to a scientific audience.
Grading
The course will be worth 6 credits and graded as “pass “or “fail.” A student who attends each session, actively participates in the discussions, and completes both written and oral assignments in a satisfactory manner will receive a passing grade.
Field Trip
Many advances in directed evolution have been pioneered by members of the Cambridge community. In Week 8, we will have a virtual field trip*, hosted by Dr. Caitlin Allen from Zymergen - a leading biotechnology company using directed evolution and robotics to produce high value products in microbial hosts. Additionally, we will be featuring a guest discussion* with Dr. Ahmed Badran of Scripps Research (San Diego, CA) who will provide their expert perspective on directed evolution from an academic perspective, discuss their career in this field, and their vision of its future directions.
*Please note: the field trip and guest discussion apply only to the on-campus course taught at MIT.
Course Expectations and Policies
Students should…
- In all situations, display respect, tolerance, and patience when interacting with colleagues.
- Be open to the learning and study strategies explored in class and the thoughts of peers.
- Seek out clarification and additional information through resources like Wikipedia, YouTube, and/or the recommended accompanying literature.
- Late assignments will be tolerated within reason but students run a risk of serious penalties if assignments and homework is not completed as scheduled without good reason or permission from the course coordinator (for example, a medical issue, family bereavement, and other unavoidable disruptions).
Our values as a classroom
Our institution values an inclusive and respectful environment where each student feels comfortable, open, and able to learn. I support these values, and I hope to foster a sense of community in this classroom and consider this classroom to be a place where you will be treated with respect. I welcome individuals of all backgrounds, beliefs, ethnicities, national origins, gender identities, sexual orientations, religious and political affiliations – and other visible and nonvisible differences.
All members of this class are expected to contribute to a respectful, welcoming, and inclusive environment for every other member of the class. If this standard is not being upheld, please feel free to contact me. Prior to course commencement I will provide a link to an anonymous feedback platform where you can share any concerns or feelings about the class environment, my teaching, or your peers, at any time.
Calendar
| Week # | Topics |
|---|---|
| 1 | Introduction |
| 2 | In vitro Gene Diversification |
| 3 | In vivo Gene Diversification |
| 4 | Selection Methods |
| 5 | Screening Methods |
| 6 |
Continuous Evolution Mid-semester Assignment Due |
| 7 | Addressing Climate Change |
| 8 |
Engineering Waste Solutions Virtual Field Trip: Dr. Caitlin Allen (Scientist, Zymergen Boston) |
| 9 | Developing Therapeutics |
| 10 |
Understanding Evolutionary Processes Paper Selection for Final Presentations Due |
| 11 | Next-Generation Directed Evolution |
| 12 |
Next-Generation Directed Evolution Virtual Visit: Dr. Ahmed Badran (Assistant Professor, Scripps Research) |
| 13 | Final Presentations |
