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Related Concept Videos

Termination of Translation01:44

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The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
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Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
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Ribosomes01:27

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Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that synthesize large quantities of protein—such as secretory cells in the human pancreas—can contain millions of ribosomes.
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Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
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Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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RIBO-seq in Bacteria: a Sample Collection and Library Preparation Protocol for NGS Sequencing
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Machine Learning Guided Batched Design of a Bacterial Ribosome Binding Site.

Mengyan Zhang1,2,3, Maciej Bartosz Holowko4,5, Huw Hayman Zumpe4,5

  • 1Machine Learning and Artificial Intelligence Future Science Platform, CSIRO, Canberra, ACT 2601, Australia.

ACS Synthetic Biology
|June 15, 2022
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Summary
This summary is machine-generated.

Researchers developed a machine learning-guided Design-Build-Test-Learn cycle to optimize bacterial ribosome binding sites (RBS). This approach enables reliable design of genetic parts, achieving up to 34% higher translation rates.

Keywords:
genetic part designmachine learningoptimizationribosome binding site

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Area of Science:

  • Synthetic Biology
  • Computational Biology
  • Molecular Biology

Background:

  • Optimizing gene expression is crucial for organism design.
  • Ribosome binding sites (RBS) control translation initiation but are challenging to design.
  • Lack of reliable methods hinders the engineering of specific genetic parts.

Purpose of the Study:

  • To develop a machine learning-guided Design-Build-Test-Learn (DBTL) cycle for bacterial RBS design.
  • To demonstrate reliable design of genetic parts using small, high-quality datasets.
  • To validate the efficacy of machine learning in engineering genetic control elements.

Main Methods:

  • Utilized Gaussian Process Regression for the 'Learn' phase.
  • Employed the Upper Confidence Bound multiarmed bandit algorithm for the 'Design' phase.
  • Integrated machine learning with laboratory automation and high-throughput screening for data generation.

Main Results:

  • Successfully designed and experimentally validated RBS variants with high translation initiation rates.
  • Achieved up to 34% increase in translation initiation rates compared to a benchmark RBS.
  • Completed four DBTL cycles, testing a total of 450 RBS variants.

Conclusions:

  • Machine learning is a powerful tool for the rational design of RBS.
  • The developed DBTL cycle enables reliable engineering of genetic parts.
  • This work paves the way for designing more complex genetic devices.