Engineering ribosomes for designer bioproduction and antibiotic discovery



Biological engineers routinely harness the predictability of the central dogma to modify living organisms. This rule cannot be generally extended to manipulations of the central dogma itself, as even minor perturbations can have significant and often deleterious consequences on cellular viability. One such case is the ribosome, a colossal multi-component protein factory that functions as the nexus for cellular information and signaling events, integrating nutrient availability with growth dynamics and resource allocation.

Our lab is developing and applying methodologies to study the translation machinery of the cell using engineered orthogonal transcription-translation networks, overcoming challenges associated with ribosomal manipulation in vivo and providing a framework for high-throughput ribosomal interrogation. Our current work is focused on the (1) dissection of putative processivity-fidelity relationships during translation, (2) experimental validation of ribosomal divergence across prokaryotes, (3) prediction of ribosome-small molecule interactions and putative antibiotic resistance mechanisms, and (4) evaluating potential routes for evolution of the modern ribosome.

Our work is supported by the Broad Institute of MIT & Harvard, the NIH Director’s Early Independence Award, and the National Aeronautics and Space Administration.



The Badran Lab will be moving to Scripps Research in the summer of 2021! 

Interested in antibiotics development, genetic code expansion and/or improving carbon fixation? We’re actively recruiting on all fronts!

January 2021 – Article published at Nature Communications

Orthogonal Translation Enables Heterologous Ribosome Engineering in E. coli has been published in Nature Communications. A feature article published by the Broad Institute can be found here. Congrats to the whole team!

December 2020 – Alan’s artwork is featured on the cover of Trends in Biotechnology

Alan designed the cover of Trends in Biotechnology to complement his review Synthetic Biological Circuits within an Orthogonal Central Dogma. 

January 13, 2020 – Alan joins the Badran Lab

Dr. Alan Costello has joined the Badran Lab after working at the National Institute for Cellular Biotechnology in Dublin, Ireland. He will be working on ribosome minimization. Welcome Alan!


Ahmed H. Badran, Ph.D.  

Principal Investigator

Ahmed H. Badran is a Principal Investigator and Fellow of the Broad Institute of MIT & Harvard. Dr. Badran earned his B.Sc. in Biochemistry & Molecular Biophysics, as well as Molecular & Cellular Biology, from the University of Arizona. Subsequently, he earned his Ph.D. in Chemical Biology from Harvard University under the guidance of Prof. David R. Liu, leading the development and application of rapid methods for continuous directed evolution. Badran has earned several distinctions for his undergraduate and graduate research, including the Arnold and Mabel Beckman Scholarship, the National Science Foundation Graduate Research Fellowship, the Harvard Graduate School of Arts and Sciences Merit Fellowship, and the National Institutes of Health Director’s Early Independence Award.

Badran_Headshot 2
G Carver 2

Gavriela Carver
Research Associate I


Alan Costello
Postdoctoral Associate


Erika DeBenedictis
Graduate Student


Ranan Fattal
Research Associate I

Natalie Kolber 1

Natalie Kolber
Research Associate I


Stefan Wan
Undergraduate Researcher

Former Lab Members


Sinisa Bratulic
Postdoctoral Associate I


Fan Liu
Postdoctoral Associate I


Rajiv Movva
Undergraduate Researcher


Meredith Fedorov
Administrative Assistant


Orthogonal Translation

The ribosome plays a central role in orchestrating responses to nutrients and extracellular stimuli. As even minor perturbations to the ribosome can have a profound impact on cellular viability, we have devised synthetic translational machinery that operates orthogonally to the host apparatus and allows us to study cellular translation with comparative ease. Through this orthogonal translation system, we are motivated to probe the factors that contribute to balancing translational fidelity and processivity in vivo.

Heterologous Ribosomes

The modern interpretation of the tree of life relies on conservation of ribosomal RNA sequences. To generalize the analysis of ribosomal component divergence, we have developed a pipeline for the production of heterologous ribosomes in E. coli. Our efforts have provided insight into the evolution of the prokaryotic ribosome and constraints that lead to the modern mitochondrial translation. This platform has further facilitated the study of extant ribosomes from disparate species while obviating safety considerations and difficulties in microbe culturing.

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Evolution of Antibiotic Resistance

With a dwindling arsenal of antibiotics to combat human microbial pathogens, mechanisms to rapidly and robustly predict antibiotic resistance can inform best practices for antibiotic dissemination and stewardship. By combining state-of-the-art techniques from synthetic biology and directed evolution, we are actively working on a high-throughput technique for the prediction of antibiotics resistance mechanisms in bacteria. In addition to identifying putative resistance mechanisms in patients, this analysis can be leveraged to inform the impact of antibiotic combinations and treatment regimens on the rate and frequency of antibiotic resistance.

Directed Evolution

Multiplex Suppression of Quadruplet Codons via tRNA Directed Evolution
DeBenedictis E*
, Carver GD*, Chung C, Söll D, Badran AH.
Submitted 2021

Continuous Directed Evolution of Ribosomal RNAs for Enhanced Activity In Vivo
Liu F*
, Bratulic S*, Costello A*, Badran AH.
Submitted 2021

Clinically relevant mutations in core metabolic genes confer antibiotic resistance
Lopatkin AJ, Bening SC, Manson AL, Stokes JM, Kohanski MA, Badran AH, Earl AM, Cheney NJ, Yang JH, Collins JJ.
Science 2021 PDF

Continuous Bioactivity-dependent Evolution of an Antibiotic Biosynthetic Pathway
Johnston C, Badran AH, Collins JJ.
Nature Communications 2020 PDFSI

Continuous Directed Evolution of Proteins with Improved Soluble Expression
Wang T, Badran AH, Huang TP, Liu DR.
Nature Chemical Biology 2018 PDF SI

Modern Methods for Laboratory Diversification of Biomolecules
Bratulic SBadran AH.
Current Opinion in Chemical Biology 2017 PDF

Continuous Evolution of Bacillus thuringiensis Toxins Overcomes Insect Resistance
Badran AH, Guzov VM, Huai Q, Kemp MM, Vishwanath P, Kain W, Nance AM, Evdokimov A, Moshiri F, Turner KH, Wang P, Malvar T, Liu DR.
Nature 2016 PDF / SISI2 

Development of Potent In Vivo Mutagenesis Plasmids with Broad Mutational Spectra
Badran AH, Liu DR.
Nature Communications 2016 PDF / SI 

Continuous Directed Evolution of DNA-Binding Domains Generates TALENs with Improved DNA Cleavage Specificity
Hubbard BP, Badran AH, Zuris JA, Guillinger JP, Davis KM, Chen L, Tsai SQ, Joung JK, Liu DR.
Nature Methods 2015 PDF / SI 

In Vivo Continuous Directed Evolution
Badran AH, Liu DR.
Current Opinion in Chemical Biology 2015 PDF 

A System For the Continuous Directed Evolution of Proteases Rapidly Reveals Drug-Resistance Mutations
Dickinson BC*, Packer MS*, Badran AH, Liu DR.
Nature Communications 2014 PDF / SI 

Negative Selection and Stringency Modulation in Phage-Assisted Continuous Evolution
Carlson JC, Badran AH, Guggiana-Nilo DA, Liu DR.
Nature Chemical Biology 2014 PDF / SI 


Badran Lab
The Broad Institute of MIT & Harvard University
Room 2018 (Office), Room 2100 (Lab)
415 Main Street
Cambridge, MA 02142
United States

Tel.: (617) 714-7144 (Office)

Administrative Assistant

Orysell Rivera

The Broad Institute of MIT & Harvard is a world-renowned collaborative and multidisciplinary research institution committed to addressing medical challenges across the world. We are actively looking for passionate, highly motivated scientists to join our team. Scientists interested in directed evolution, ribosomal biology, antibiotics development and/or the origins of cellular translation are encouraged to apply! Prior training in any fields spanning biology, chemistry, or computational sciences is preferred but not required.
If interested, please email Ahmed at with your CV (including a list of references) and summary of your prior research.