On February 17^th 2023, the third part of the online symposium series jointly organized by Science/AAAS and Westlake University, entitled “Protein Engineering”, was successfully hosted with a full lineup of globally-renowned researchers: Dr. Bradley L. Pentelute (MIT), Dr. Virginia W. Cornish (Columbia University) and Dr. Ahmed H. Badran (The Scripps Research Institute) all shared their latest insights on chemical protein synthesis, cell and synthetic biology and introduced the latest advances in unnatural amino acid technology.

The three top researchers from the field of protein chemistry and engineering research were also joined by Dr. Bobo Dang (Westlake University) and Dr. Michael Funk (Editor-in-Chief of Science/American Association for the Advancement of Science), who co-chaired the sessions.

This successful third part to the symposium series was enjoyed live by over 10,400 viewers from across the world, with global audience members comprising of fellow researchers, academics, scientists and students from universities, hospitals, scientific research institutions and pharmaceutical companies. The online symposium series promotes a platform for open dialogue and a discussion of topics and cutting-edge ideas, with viewers encouraged to submit their questions and ideas surrounding the future directions of the research field.

SPEAKERS

Dr. Bradley L. Pentelute, Massachusetts Institute of Technology

Topic: “Rapid flow synthesis of proteins”

Dr. Virginia W. Cornish, Columbia University

Topic: “Expanding the Synthetic Capabilities of Yeast”

Dr. Ahmed H. Badran, The Scripps Research Institute

Topic: “Rewriting Life’s Code: Towards An Orthogonal Information Encoding–Decoding System in Living Cells”

CO-CHAIRS

Dr. Bobo Dang, Principal Investigator, School of Life Sciences, Westlake University

Dr. Michael Funk, Editor-in-Chief of Science/American Association for the Advancement of Science

RESEARCH HIGHLIGHTS

Proteins are the molecules that give cells shape and form, perform chemical reactions that enable replication and metabolism, and enable cells and organisms to sense and respond to their environments. Tools in protein chemistry and engineering have transformed our ability to understand molecular processes in biology, create new therapies and diagnostics in the biomedical realm, and harness evolution to develop biological catalysts not seen in nature.

In the ‘Protein Engineering’ symposium, the three distinguished researchers shared their cutting-edge work in this field, which sits as a crucial bridge at the interface of biology and chemistry.

Dr. Bradley L. Pentelute, professor in the Department of Chemistry at the Massachusetts Institute of Technology, opened proceedings with his presentation on “Rapid flow synthesis of proteins." Solid-phase synthesis of homogenous peptides longer than 50 amino acids has been a long-standing challenge due to inefficient coupling and side reactions. Dr. Pentelute's research group has used an automated chemical platform to optimize rapid flow-based peptide synthesis and successfully achieved the synthesis of various single-domain proteins, including insulin precursor and HIV-1 protease containing multiple non-natural amino acids.

After refolding, these proteins are almost indistinguishable from recombinant proteins, and the activity of the synthesized enzymes is close to that of ribosome-synthesized enzymes. This method enables the rapid and on-demand synthesis of small proteins with a large precursor amino acid library. Automated machines can complete the synthesis of single-domain proteins in a few hours. In addition, Dr. Bradley L. Pentelute pointed out that this technology can play an important role in the synthesis of mirror-image proteins (D-protein) and mirror phage display. Conventional D-protein synthesis requires the synthesis of multiple peptide fragments and several native chemical ligations, while rapid flow synthesis can directly achieve the full-length synthesis of Mirror-image proteins in a shorter time, greatly improving the efficiency of mirror phage screening and promoting the development of D-peptide drugs. Finally, Dr. Pentelute expects to use machine learning and other computational technologies to collect high-quality data widely and further improve fast-flow peptide synthesis, promoting autonomous protein design and production.

Dr. Virginia W. Cornish of Columbia University focused her talk on the “Expanding the Synthetic Capabilities of Yeast”. Dr. Cornish's research team has successfully developed a yeast system that can detect pathogens. They have demonstrated that by using yeast test papers, pathogen detection can be completed in a short period of time in the real world. Dr. Cornish also introduced another major research direction, which is to use yeast directly to treat diseases. Her team has developed a new method that uses yeast to treat diabetic wounds. Dr. Cornish wants to try using yeast to directly secrete epidermal growth factor (EGF) to promote wound healing. Experimental results show that mice in the yeast experimental group that can secrete EGF have faster wound healing rates. Immunohistochemical data also indicate that the experimental group has thicker skin, more proliferating keratinocytes, and more abundance of new blood vessels.

Dr. Cornish believes that using synthetic biology to transform yeast cells to have new structures and functions is similar to her early academic career in synthesizing small molecules. Both involve using basic modules to create new things, and she believes that this approach can provide new treatment methods for different diseases. Dr. Cornish's report systematically summarizes the important work of his academic career, from small molecules to proteins, and finally to cell building blocks, allowing us to appreciate the charm of bioengineering.

Dr. Ahmed H. Badran from The Scripps Research Institute delivered his topic ‘Rewriting Life’s Code: Towards An Orthogonal Information Encoding–Decoding System in Living Cells’, which emphasized that despite there being many forms of life on earth, the interesting fact is that almost all life is assembled from the same components. For example, there are many types of proteins, but only 20 kinds of amino acids make up proteins. Dr. Badran believes that if we can engineer codons to generate non-canonical amino acids (ncAAs) with new side chains or backbones, then we can obtain proteins with potentially entirely new functions.

However, the process of synthesizing proteins is very complex and requires the coordinated operation of tRNA synthetases, ribosomes, mRNAs, tRNAs, and codons. If non-natural amino acids are to be introduced, all of these components need to be altered. Dr. Badran's research team used a phage-assisted continuous evolution system (PACE) to engineer ribosomes, making modified codons more easily recognizable and increasing the efficiency of non-natural amino acid insertion. At the same time, based on the quadruple codon, the Badran research team used PACE-directed evolution to screen multiple qtRNAs, making them able to specifically recognize quadruple codons corresponding to different amino acids. In future research, Dr. Badran will continue to optimize the mRNA and tRNA components.

We would like to sincerely thank the three distinguished guest speakers, Dr. Bradley L. Pentelute, Dr. Virginia W. Cornish, and Dr. Ahmed H. Badran, and two co-chairs Dr. Bobo Dang and Dr. Michael Funk for their in-depth and insightful discussions in the field of ‘Protein Engineering’, and also extend our thanks to the audience members who were very engaged throughout the sessions. During the dialogues, we heard a number of different viewpoints and innovative ideas, as well as insightful back-and-forths between the guests – of which will be very useful to anyone interested in these areas and conducting research work.

To enjoy the full playback and open discussion of ‘Protein Engineering’ jointly organized by Science/AAAS and Westlake University, please visit: https://live.vhall.com/v3/lives/watch/537973129

Please check out the previous parts to this symposium series and we very much look forward to you joining us in our coming parts as we work towards an open and global platform for scientific discussion and innovation.

Science/AAAS and Westlake University Symposium Series

Part 1 | Gene Editing | https://live.vhall.com/v3/lives/watch/925591016

Part 2 | Biomolecular Condensates | https://live.vhall.com/v3/lives/watch/340760384

Part 3 | Protein Engineering | https://live.vhall.com/v3/lives/watch/537973129

Part 4 | Dynamic Molecular Systems | Time/Date: 8-10 pm, March 30, 2023 (ET) / 8-10 am, March 31, 2023 (UTC+8)