ChemBio Seminar by Prof. Matt Shoulders (Massachusetts Institute of Technology Department of Chemistry) – CH-636
Event details
| Date | 03.10.2023 |
| Hour | 16:15 › 17:15 |
| Location | |
| Category | Conferences - Seminars |
| Event Language | English |
Title: Enabling Continuous Directed Evolution in Complex Systems
Abstract :
A key limitation of all directed evolution workflows performed in test tubes, Escherichia coli, or yeast is that these approaches often yield products that fail to function when introduced into relevant settings, such as valuable bacterial species, plants, and especially mammalian cells. Instead, functions evolved in other or simpler systems are often derailed in these environments by off-target interactions, poor stability, inappropriate modification/localization, or many other serious problems. This frontier challenge could theoretically be addressed by always leveraging the relevant cell system itself as the design, engineering, and quality control factory for biomolecule discovery and optimization. With these challenges in mind, we developed the first rapid and efficient system for continuous directed evolution directly in living mammalian cells. In our approach, essentially a mammalian phage-assisted continuous evolution (mPACE) platform, the ability of a highly error-prone adenovirus to propagate is coupled to the activity of a biomolecule of interest within the human cell itself. The system is designed for safety, speed, and ease-of-use. Critically, mutagenesis, selection, and amplification all occur concurrently in this platform, maximizing the benefits of natural selection and the throughput of experiments. I will discuss progress in the application of mammalian cell-based continuous directed evolution to the engineering of desired biomolecule functions in human cells. I will also discuss the development of advanced targeted mutagenesis techniques based on our MutaT7 platform, which can enable continuous directed evolution in many diverse cell and in vivo settings.
Biography:
Matt Shoulders completed his BS in Chemistry at Virginia Tech in 2004 and his PhD in Chemistry at the University of Wisconsin–Madison in 2009. After a stint as an American Cancer Society Postdoctoral Fellow at Scripps Research Institute in La Jolla, CA, he began his independent career at MIT in 2012, where he was promoted to Associate Professor in 2017 and Full Professor in 2022. Matt’s group studies how cells fold proteins and develops and applies technologies for in vivo evolution. His lab’s work has earned numerous awards, including the NIH Director’s New Innovator Award, the NSF CAREER Award, and the Smith Family Foundation’s Excellence in Biomedical Research Award. He has also been recognized as a Camille-Dreyfus Teacher-Scholar, an American Cancer Society Research Scholar, and the 56th Edward Mallinckrodt, Jr. Foundation Faculty Scholar. Matt is a MacVicar Faculty Fellow at MIT, in recognition of outstanding contributions to undergraduate education and mentorship, and has received MIT’s Committed to Caring Award for Outstanding Graduate Student Mentoring.
Lab Website: https://shoulderslab.mit.edu
Abstract :
A key limitation of all directed evolution workflows performed in test tubes, Escherichia coli, or yeast is that these approaches often yield products that fail to function when introduced into relevant settings, such as valuable bacterial species, plants, and especially mammalian cells. Instead, functions evolved in other or simpler systems are often derailed in these environments by off-target interactions, poor stability, inappropriate modification/localization, or many other serious problems. This frontier challenge could theoretically be addressed by always leveraging the relevant cell system itself as the design, engineering, and quality control factory for biomolecule discovery and optimization. With these challenges in mind, we developed the first rapid and efficient system for continuous directed evolution directly in living mammalian cells. In our approach, essentially a mammalian phage-assisted continuous evolution (mPACE) platform, the ability of a highly error-prone adenovirus to propagate is coupled to the activity of a biomolecule of interest within the human cell itself. The system is designed for safety, speed, and ease-of-use. Critically, mutagenesis, selection, and amplification all occur concurrently in this platform, maximizing the benefits of natural selection and the throughput of experiments. I will discuss progress in the application of mammalian cell-based continuous directed evolution to the engineering of desired biomolecule functions in human cells. I will also discuss the development of advanced targeted mutagenesis techniques based on our MutaT7 platform, which can enable continuous directed evolution in many diverse cell and in vivo settings.
Biography:
Matt Shoulders completed his BS in Chemistry at Virginia Tech in 2004 and his PhD in Chemistry at the University of Wisconsin–Madison in 2009. After a stint as an American Cancer Society Postdoctoral Fellow at Scripps Research Institute in La Jolla, CA, he began his independent career at MIT in 2012, where he was promoted to Associate Professor in 2017 and Full Professor in 2022. Matt’s group studies how cells fold proteins and develops and applies technologies for in vivo evolution. His lab’s work has earned numerous awards, including the NIH Director’s New Innovator Award, the NSF CAREER Award, and the Smith Family Foundation’s Excellence in Biomedical Research Award. He has also been recognized as a Camille-Dreyfus Teacher-Scholar, an American Cancer Society Research Scholar, and the 56th Edward Mallinckrodt, Jr. Foundation Faculty Scholar. Matt is a MacVicar Faculty Fellow at MIT, in recognition of outstanding contributions to undergraduate education and mentorship, and has received MIT’s Committed to Caring Award for Outstanding Graduate Student Mentoring.
Lab Website: https://shoulderslab.mit.edu
Practical information
- Informed public
- Free