Synthetic Biology

Spheroplasted cells: a game changer for DNA delivery to diatoms

1. E.J.L. Walker
2. M. Pampuch
3. G. Tran
4. B.J.K. Karas

Reviewed by Arcadia Science

Mapping targetable sites on the human surfaceome for the design of novel binders

1. Petra E. M. Balbi
2. Ahmed Sadek
3. Anthony Marchand
4. Ta-Yi Yu
5. Jovan Damjanovic
6. Sandrine Georgeon
7. Joseph Schmidt
8. Simone Fulle
9. Che Yang
10. Hamed Khakzad
11. Bruno E. Correia

Reviewed by Arcadia Science

High resolution deep mutational scanning of the melanocortin-4 receptor enables target characterization for drug discovery

1. Conor J Howard
2. Nathan S Abell
3. Beatriz A Osuna
4. Eric M Jones
5. Leon Y Chan
6. Henry Chan
7. Dean R Artis
8. Jonathan B Asfaha
9. Joshua S Bloom
10. Aaron R Cooper
11. Andrew Liao
12. Eden Mahdavi
13. Nabil Mohammed
14. Alan L Su
15. Giselle A Uribe
16. Sriram Kosuri
17. Diane E Dickel
18. Nathan B Lubock

• Curated by eLife

  eLife Assessment

  The authors use deep mutational scanning to assess the effect of all possible protein-coding variants in MC4R, a G protein-coupled receptor associated with obesity. They develop new, more precise approaches, enabling them to probe molecular phenotypes directly relevant to the development of drugs that target this receptor. In this important work, the authors provide convincing evidence that variants impact signaling through MC4R in different ways, that some defective variants are amenable to a corrector drug and that deep mutational scanning data could guide compound optimization.

Reviewed by eLife

Chai-1: Decoding the molecular interactions of life

1. Chai Discovery
2. Jacques Boitreaud
3. Jack Dent
4. Matthew McPartlon
5. Joshua Meier
6. Vinicius Reis
7. Alex Rogozhnikov
8. Kevin Wu

Reviewed by PREreview

A molecular proximity sensor based on an engineered, dual-component guide RNA

1. Junhong Choi
2. Wei Chen
3. Hanna Liao
4. Xiaoyi Li
5. Jay Shendure

• Curated by eLife

  eLife Assessment

  This important manuscript describes a creative approach using dual-component gRNAs to create a new class of molecular proximity sensors for genome editing. The authors demonstrate that this tool can be coupled with several different gene editing effectors, showing convincingly that the tool functions as intended. This study not only introduces a first-of-its kind approach, but through careful measurements also enables future further development of the technology.

Reviewed by eLife

De novo-designed minibinders expand the synthetic biology sensing repertoire

1. Zara Y Weinberg
2. Sarah S Soliman
3. Matthew S Kim
4. Devan H Shah
5. Irene P Chen
6. Melanie Ott
7. Wendell A Lim
8. Hana El-Samad

• Curated by eLife

  eLife Assessment

  This study presents a useful investigation of the use of small, de novo-designed protein binding domains (mini-binders) against the Spike protein of SARS-CoV-2 and EGFR, as ligand binding domains on two classes of synthetic receptors, second-generation synNotch (SNIPR) and CAR. The methods and evidence supporting the focused claims are solid. This work will be of interest to synthetic biologists and cell engineers as a starting point to map out the rules for receptor engineering based on mini-binders and ultimately to advance them in biomedical applications.

Reviewed by eLife

A synthetic method to assay polycystin channel biophysics

1. Megan Larmore
2. Orhi Esarte Palomero
3. Neha Kamat
4. Paul G DeCaen

• Curated by eLife

  eLife Assessment

  The authors have developed a valuable approach that employs cell-free expression to reconstitute ion channels into giant unilamellar vesicles for biophysical characterisation. The work is convincing and will be of particular interest to those studying ion channels that primarily occur in organelles and are therefore not amenable to be studied by more traditional methods.

Reviewed by eLife

Light-driven synchronization of optogenetic clocks

1. Maria Cristina Cannarsa
2. Filippo Liguori
3. Nicola Pellicciotta
4. Giacomo Frangipane
5. Roberto Di Leonardo

• Curated by eLife

  eLife assessment

  This study presents a light-entrainable synthetic oscillator in bacteria, the optorepressilator. The authors develop a toolbox using optogenetics that makes the cellular oscillator easily controllable. This toolbox is valuable, contributing both to bioengineering and to the understanding of biological dynamical systems. The comparison with a mathematical model, population, and single-cell measurements demonstrate convincingly that the planned system was achieved and is suitable to control and study biological oscillators.

Reviewed by eLife

Design of highly functional genome editors by modeling the universe of CRISPR-Cas sequences

1. Jeffrey A. Ruffolo
2. Stephen Nayfach
3. Joseph Gallagher
4. Aadyot Bhatnagar
5. Joel Beazer
6. Riffat Hussain
7. Jordan Russ
8. Jennifer Yip
9. Emily Hill
10. Martin Pacesa
11. Alexander J. Meeske
12. Peter Cameron
13. Ali Madani

Reviewed by Arcadia Science

Intracellular Expression of a Fluorogenic DNA Aptamer Using Retron Eco2

1. Mahesh A Vibhute
2. Corbin Machatzke
3. Katrin Bigler
4. Saskia Krümpel
5. Daniel Summerer
6. Hannes Mutschler

• Curated by eLife

  eLife assessment

  This important work introduces a method to express fluorogenic DNA aptamers in E. coli, paving the way for genetically encoded fluorescent DNA. The evidence supporting the conclusions is solid, consisting of comparisons of the aptamer's activity in vitro and within bacterial cells. This advancement described in this study is likely to become a standard technique in the DNA aptamer field, and the work will be of interest and utility to researchers in synthetic biology, molecular imaging, and bacterial genetics fields.

Reviewed by eLife