Engineering ribosomes for designer bioproduction and antibiotic discovery
THE BADRAN LAB
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
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.
September 25th, 2018 – Fan receives L’Oreal Fellowship
Dr. Fan Liu has been awarded the L’Oreal USA For Women In Science Fellowship to support her study of antibiotic resistance mechanisms in bacteria. Congrats Fan!
January 14, 2018 – Alina joins the Badran Lab
Dr. Alina Chan joins us from Pamela Silver’s Lab at Harvard Medical School. She will be investigating heterologous ribosome production and antibiotics development. Welcome, Alina!
December 18, 2017 – Erika joins the Badran Lab
Erika DeBenedictis has joined the Badran Lab under the joint supervision of Drs. Bruce Tidor and Kevin Esvelt. Erika will lead efforts to engineer fully orthogonal translation in living cells. Welcome, Erika!
Ahmed H. Badran, Ph.D.
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.
Postdoctoral Associate I
HFSP Postdoctoral Fellow
Research Associate I
Postdoctoral Associate I
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.
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.
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.
Modern Methods for Laboratory Diversification of Biomolecules
Bratulic S, Badran 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 / SI / SI2
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
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