{"id":658,"date":"2018-12-07T00:40:19","date_gmt":"2018-12-07T00:40:19","guid":{"rendered":"http:\/\/protobiology.org\/wp3\/?p=658"},"modified":"2025-08-27T00:55:56","modified_gmt":"2025-08-27T00:55:56","slug":"leftovers","status":"publish","type":"post","link":"http:\/\/protobiology.org\/wp3\/2018\/12\/07\/leftovers\/","title":{"rendered":"leftovers"},"content":{"rendered":"

Building semi-synthetic minimal cells<\/h1>\n

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We are combining\u00a0top-down<\/em>\u00a0and\u00a0bottom-up<\/em>\u00a0approaches to synthetic biology; using tools of protein engineering and molecular biology, together with novel synthetic cell technologies, to understand and modulate biological processes.\u00a0
\nSynthetic minimal cells can help us studying basic properties of life, understand the origin of life on Earth, and give guidance looking for life elsewhere in the Universe. We aim at building models for studying diseases, for creating novel therapies and for making custom biofactories.\u00a0
\nWe apply engineering principles to biology: we\u00a0build life<\/em>, or\u00a0grow machines<\/em>.\u00a0This talk gives broad overview of our lab’s work.\u00a0<\/a><\/p>\n

The\u00a0top-down<\/em><\/a>\u00a0approach involves building on the biological ensemble, modifying existing cellular pathways to explore and control biology.\u00a0
\nThe\u00a0bottom-up<\/em><\/a>\u00a0approach involves building chemical systems capable of mimicking cellular processes – the synthetic minimal cells, that mimic properties of live cells. Those synthetic cells allow us studying and engineering complex biological pathways, building new biological functionalities, make better drugs and novel therapy strategies, and tracing the evolutionary history of life in model protocells.<\/p>\n

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bottom-up<\/em>\u00a0synthetic biology
\nBuilding artificial chemical systems mimicking cells<\/h1>\n

We have developed the first known system capable of non-enzymatic RNA synthesis inside model protocells.\u00a0
\nIn this work, we have shown how citric acid can stabilize fatty acid liposomes in presence of divalent cations, allowing for non-enzymatic template director RNA primer extension inside the liposomes. This discovery bridges the RNA-world hypothesis or earliest life having RNA-based metabolism with the origin of compartmentalization based on fatty acid liposomes. (Adamala and Szostak, Science 2013)
\nWe also discovered a chemically-driven replication mechanism for model protocells (Zhu, Adamala, Zhang and Szostak, PNAS 2012).
\nTogether, those projects allow for drawing a plausible, complete protocell cycle: inside the protocells, RNA is replicated by template-directed non-enzymatic synthesis, and the protocells grow into filamentous threads by absorbing fatty acid molecules from micelles and divide in response to shear stress.\u00a0<\/p>\n

\"prototypingRNA replication inside protocellsdivision via threadsRNA is encapsulated\u00a0
\nin protocellsactivated nucleotides enter\u00a0
\nvia semi-permeable bilayerRNA template is copiedSource: Adamala and Szostak, Science 2013<\/div>\n

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As part of the same overarching goal of building a chemical system capable of Darwinian evolution, we have shown that an encapsulated small peptide catalyst can impact the fitness of model protocells.\u00a0
\nI have studies catalysis of Ser-His and other di- and tri- amino acid catalytic peptides. We have shown that the minimal serine protease analogue, Ser-His, can catalyze formation of peptide nucleic acids (Gorlero et.al FEBS Letters 2009). We have also demonstrated how the same dipeptide catalyst’s activity can be enhanced by the presence of fatty acid protocell vesicles, and in turn the product of the reaction catalysed by said dipeptide allows the protocell to enhance uptake of membrane building blocks, resulting in protocell growth.\u00a0
\nThis couples the activity of encapsulated catalyst with the fitness of the protocell, in a model system exploring the origin of Darwinian selection. (Adamala and Szostak, Nature Chemistry 2013).\u00a0<\/p>\n

\"prototypingSer-His catalysed reactionSource: Adamala and Szostak, Nature Chemistry 2013<\/div>\n

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Work done with\u00a0Pier Luigi Luisi from University Roma Tre<\/a>\u00a0and\u00a0Jack Szostak from Harvard University<\/a>.<\/p>\n

\nOur most significant publications in that area:<\/p>\n

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Non-enzymatic template-directed RNA synthesis inside model protocells;<\/strong>
\nK. Adamala and J.W. Szostak,\u00a0
\nScience<\/u>\u00a0342 (2013) 1098 – 1100;
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Competition between model protocells driven by an encapsulated catalyst;<\/strong>
\nK. Adamala and J.W. Szostak,\u00a0
\nNature Chemistry<\/u>\u00a05 (2013) 495 – 501;
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Engineering genetic circuit interactions within and between synthetic minimal cells;<\/strong>
\nKatarzyna P. Adamala*, Daniel A. Martin-Alarcon*, Katriona R. Guthrie-Honea, Edward S. Boyden;
\nNature Chemistry<\/u>, 9, 431-439, 2017, doi:10.1038\/nchem.2644; *equal contribution
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Collaboration between primitive cell membranes and soluble catalysts;\u00a0<\/strong>
\nK. Adamala*, A. E. Engelhart* and J. W. Szostak;
\nNature Communications<\/u>, 2016, doi:10.1038\/ncomms11041; *equal contribution
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Full list of peer reviewed publications:\u00a0protobiology.org\/publications<\/a><\/p>\n

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Broader impact<\/h1>\n

TED talk on synthetic life<\/strong>
\nKate presented concept of building synthetic minimal cells, with its biotechnological, biomedical and basic science implications, in a\u00a0TEDx talk\u00a0<\/a>.\u00a0
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