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Expanding the genetic code

November 29, 2024 — 

UM’s Chemical Synthetic Biology and Xenobiology Laboratory focuses on changing the living cell’s chemical composition through the expansion of the genetic code. Their work aims to transform genetic code expansion from an academic pursuit into high-value, chemistry-driven biotechnology with applications in biotherapies. Dr. Ned Budisa from the department of chemistry leads this research lab. Budisa is a professor at the Faculty of Science and Tier 1 Canada Research Chair in chemical synthetic biology and xenobiology.

The lab follows an interdisciplinary approach collaborating with researchers in chemistry, microbiology and physics. Dr. Hamid Karbalaei-Heidari is a guest scientist in the chemistry department who is collaborating with Budisa to apply CRISPR-associated transposition for gene integration into cellular genomes.

“For these we are working in a specific compound of the translation machinery. We call it the Aminoacyl tRNA synthetase system or orthogonal translation system. So in this way, you can modify protein as much as you want, and then change the protein and make a new-to-nature protein which has lots of applications in therapeutics and also material science and so on. We use a novel technology, we called it CRISPR-associated transposition to genomically integrate one of these orthogonal translation systems in the Escherichia coli bacteria. And in this way, cells can produce modified protein using non-natural amino acids during the synthesis of protein.”, says Dr. Hamid Karbalaei-Heidari.

The lab has leveraged living cell machinery to incorporate over 100 unique building blocks into proteins and life chemistry. This breakthrough moves researchers closer to creating truly synthetic cells, offering new insights into life’s fundamental principles and the genetic code’s evolution. Synthetic cells also hold significant technological potential, particularly in applications like click chemistry.

“Click chemistry allows us to label proteins within living cells without disrupting their function. Our group was among the first globally to equip bacteria and proteins with these clickable amino acids building blocks, paving the way for industrial applications”, says Ned Budisa.

Additionally, Budisa underscores the responsibility of scientists to communicate their research to the public, emphasizing that “good science can be communicated in good terms,” especially when it involves synthetic biology, a field that often raises concerns about the potential escape of synthetic cells into nature.

“When we create a bacterium using artificial building blocks, it is inherently isolated, as it cannot exchange genetic material with the natural environment nor survive outside the laboratory. These building blocks differ fundamentally from those found in nature, providing our synthetic cells with built-in biosafety. We are essentially constructing an effective genetic firewall, and our laboratory data robustly confirm this”, explains Budisa.

To learn more about their research, please visit The Science Cast for their recently published article.

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