Synthetic Biology

A scalable framework for high-throughput identification of functional origins of replication in non-model bacteria

1. Charlie Gilbert
2. Stephanie L. Brumwell
3. Alexander Crits-Christoph
4. Shinyoung Clair Kang
5. Zaira Martin-Moldes
6. Wajd Alsharif
7. Ariela Esmurria
8. Mary-Anne Nguyen
9. Henry H. Lee
10. Nili Ostrov

Reviewed by Arcadia Science

Ribozyme activity modulates the physical properties of RNA–peptide coacervates

1. Kristian Kyle Le Vay
2. Elia Salibi
3. Basusree Ghosh
4. TY Dora Tang
5. Hannes Mutschler

• Curated by eLife

  eLife assessment

  Experimental models of simple cell-like compartments can help us to understand how biology operated early in its history. The authors convincingly show how the properties of coacervate droplets can be influenced by the activity of ribozymes inside them. This important result potentially provides a new route for biologists or chemists to establish cell mimics that support the evolution of biomolecules within.

Reviewed by eLife

Evolutionary-scale prediction of atomic-level protein structure with a language model

1. Zeming Lin
2. Halil Akin
3. Roshan Rao
4. Brian Hie
5. Zhongkai Zhu
6. Wenting Lu
7. Nikita Smetanin
8. Robert Verkuil
9. Ori Kabeli
10. Yaniv Shmueli
11. Allan dos Santos Costa
12. Maryam Fazel-Zarandi
13. Tom Sercu
14. Salvatore Candido
15. Alexander Rives

Reviewed by Arcadia Science

Precision engineering of biological function with large-scale measurements and machine learning

1. Drew S. Tack
2. Peter D. Tonner
3. Abe Pressman
4. Nathanael D. Olson
5. Sasha F. Levy
6. Eugenia F. Romantseva
7. Nina Alperovich
8. Olga Vasilyeva
9. David Ross

Reviewed by Review Commons

Macroscopic control of cell electrophysiology through ion channel expression

1. Mario García-Navarrete
2. Merisa Avdovic
3. Sara Pérez-Garcia
4. Diego Ruiz Sanchis
5. Krzysztof Wabnik

• Curated by eLife

  eLife assessment

  This manuscript will be of interest to those working on non-neuronal bioelectricity, particular synthetic biologists and bioengineers. The primary contribution is the ability to leverage engineered gene circuits to control cellular membrane potential. We find issue, however, with the presentation of the data in this work as electrical communication since the synchronous behavior largely arises from external chemical stimuli.

Reviewed by eLife

Resurrecting essential amino acid biosynthesis in mammalian cells

1. Julie Trolle
2. Ross M McBee
3. Andrew Kaufman
4. Sudarshan Pinglay
5. Henri Berger
6. Sergei German
7. Liyuan Liu
8. Michael J Shen
9. Xinyi Guo
10. J Andrew Martin
11. Michael E Pacold
12. Drew R Jones
13. Jef D Boeke
14. Harris H Wang

• Curated by eLife

  Evaluation Summary:

  In this study, Trolle et al aimed to introduce methionine, threonine, isoleucine, and valine biosynthetic pathways into Chinese Hamster Ovary (CHO) cells. While this was unsuccessful for methionine, threonine, and isoleucine, introduction of valine synthesis rendered CHO cells partially independent on exogenous valine. Although introduction of essential amino acid biosynthetic pathways into mammalian cells is of potentially broad interest to the fields of synthetic biology, biotechnology and metabolism, there were concerns regarding incomplete demonstration that the introduction of valine pathway into CHO cells is sufficient to sustain homeostasis in the absence of exogenous valine. Further metabolic/biochemical characterization of valine-producing CHO cells is warranted.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their names with the authors.)

Reviewed by eLife

A Pan-Coronavirus Vaccine Candidate: Nine Amino Acid Substitutions in the ORF1ab Gene Attenuate 99% of 365 Unique Coronaviruses: A Comparative Effectiveness Research Study

1. Eric Luellen

Reviewed by ScreenIT

De novo-designed transmembrane domains tune engineered receptor functions

1. Assaf Elazar
2. Nicholas J Chandler
3. Ashleigh S Davey
4. Jonathan Y Weinstein
5. Julie V Nguyen
6. Raphael Trenker
7. Ryan S Cross
8. Misty R Jenkins
9. Melissa J Call
10. Matthew E Call
11. Sarel J Fleishman

• Curated by eLife

  Evaluation Summary:

  This is an interesting paper that uses de novo protein design to probe the effects of oligomerization state on the activity of chimeric antigen receptors (CARS). The successful design of transmembrane domains with specific oligomeric states is an impressive result on its own. The proteins were designed using rotamer-based sequence optimization in Rosetta with an energy function specific for the membrane environment. After experimentally evaluating a couple rounds of designs, the investigators settled on a design protocol that also included screening of the design candidates with docking simulations in alternative oligomerization states to check that the sequences preferred the desired oligomerization state. The designs were experimentally evaluated with gel electrophoresis and X-ray crystallography. In the end, designs that adopted well-defined dimers, trimers, or tetramers were created and carried forward in experiments as CARs.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Accelerating PERx reaction enables covalent nanobodies for potent neutralization of SARS-CoV-2 and variants

1. Bingchen Yu
2. Shanshan Li
3. Takako Tabata
4. Nanxi Wang
5. Li Cao
6. G. Renuka Kumar
7. Wei Sun
8. Jun Liu
9. Melanie Ott
10. Lei Wang

Reviewed by ScreenIT

Dynamic spreading of chromatin-mediated gene silencing and reactivation between neighboring genes in single cells

1. Sarah Lensch
2. Michael H Herschl
3. Connor H Ludwig
4. Joydeb Sinha
5. Michaela M Hinks
6. Adi Mukund
7. Taihei Fujimori
8. Lacramioara Bintu

• Curated by eLife

  Evaluation Summary:

  This study describes a novel approach to investigate how the transcriptional repressors KRAB and HDAC4 repress gene expression, how repression spreads over differing genomic distances, and what the role of insulator elements is in blocking the spread of repression and in reactivation of repressed genes. The results of this study allow modeling of the coordinated repression or activation of closely linked genes and should be of wide interest to researchers interested in chromatin and gene expression.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife