Engineering new cell functionalities on thin condensates

RESEARCH HIGHLIGHT

25 August – Researchers at the Institute of Molecular Biology (IMB) and Johannes Gutenberg University Mainz (JGU) have developed a method to engineer new functionalities into cells. The results were published today in the journal Cell in the article "Dual film-like organelles enable spatial separation of orthogonal eukaryotic translation".

Numerous processes occur inside living cells, from DNA replication and repair to protein synthesis and recycling. In order to organise this plethora of reactions, they must be separated in three-dimensional space. One way eukaryotic cells do this is by extruding a piece of membrane to form a membrane-enclosed space – an organelle – in which specific functions can take place. Alternatively, the cell can also segregate molecules into distinct areas (so-called membraneless organelles) through phase separation, a phenomenon similar to the separation of vinegar and oil in a salad dressing. Such membraneless organelles have advantages: as they are not separated from the rest of the cell by a membrane barrier, large molecules can get in and out more easily. Membrane-enclosed organelles therefore operate like separate “rooms” in a cell, while membraneless organelles operate like different corners of the same room.

One of the most important processes in the cell is protein synthesis, where the RNA code is translated into a protein code, which contains the blueprint for making proteins. These codes are like the languages of the cell. If an organelle could be engineered and dedicated to translate the RNA code in new ways (i.e. use a different language), the functions of the resulting protein could also be changed, endowing it with unique properties that could be used, for example, to switch its functions on or off, or to allow the protein to be visualised in living cells.

In 2019, Prof. Edward Lemke and his research team succeeded in creating an artificial membraneless organelle that translated the RNA code using a new code, or language, without interfering with RNA translation in the rest of the cell. Now Edward and a student from his lab, Christopher Reinkemeier, have further built on this success by creating film-like organelles that can be used to subdivide cell processes into even smaller spaces. "The biggest gain is that we were able to create extremely small reaction spaces – this way we can have several of them in a cell at the same time," explains Prof. Lemke. "We have converted the large 3D organelles into 2D organelles on a membrane surface, and can even run complicated biochemical reactions in these thin layers." Using these thinner organelles, the same cell can now translate the RNA code into three different languages – thus creating three different proteins – in different "corners of the same room", without the translations interfering with each other. This means that the same protein can now have three different functions, depending on which “corner” it was made in.

This novel method not only allows scientists to engineer proteins with unique functions, but also helps them to better understand how eukaryotic cell functions evolve. "We can find out more about how complicated functions occur in the membrane space, what unique functionalities the membrane has, and what special reaction spaces are created there when you concentrate proteins using 2D phase separation," says Dr Reinkemeier. "Through engineering these film-like organelles, we can also better understand how nature also uses such mechanisms to create proteins with new functions."

_{Cheryl Li is a Science Writer at the Institute of Molecular Biology (IMB).}

_{The above image, inspired by Dalí’s works, shows that equipping eukaryotic cell with thin, film-like designer organelles is a powerful way to introduce multiple new functionalities into cells. Image © Sara Mingu.}

^{Further details}

^{Further information can be found at https://www.cell.com/cell/fulltext/S0092-8674(21)00943-0}

^{Edward Lemke is an Adjunct Director at IMB and a Professor of Synthetic Biophysics at Johannes Gutenberg University Mainz. Further information about research in the Lemke lab can be found at www.imb.de/lemke}

^{About the Institute of Molecular Biology gGmbH}

^{The Institute of Molecular Biology gGmbH (IMB) is a centre of excellence in the life sciences that was established in 2011 on the campus of Johannes Gutenberg University Mainz (JGU). Research at IMB focuses on three cutting-edge areas: epigenetics, developmental biology, and genome stability. The institute is a prime example of successful collaboration between a private foundation and government: The Boehringer Ingelheim Foundation has committed 154 million euros to be disbursed from 2009 until 2027 to cover the operating costs of research at IMB. The State of Rhineland-Palatinate has provided approximately 50 million euros for the construction of a state-of-the-art building and is giving a further 52 million in core funding from 2020 until 2027. For more information about IMB, please visit: www.imb.de}

^{About Johannes Gutenberg University Mainz}

^{Johannes Gutenberg University Mainz (JGU) is a globally recognized research-driven university with around 31,500 students. Its main core research areas are in particle and hadron physics, the materials sciences, and translational medicine, while its most outstanding research achievements in the humanities have been attained in the fields of American Studies and Historical Cultural Studies. JGU's academic excellence is reflected in its success in the Excellence Initiative of the German federal and state governments: In 2012, the university's Precision Physics, Fundamental Interactions and Structure of Matter (PRISMA) Cluster of Excellence was approved and the funding of its Materials Science in Mainz (MAINZ) Graduate School of Excellence was extended. Moreover, excellent placings in national and international rankings, as well as numerous other honors and awards, demonstrate just how successful Mainz-based researchers and academics are. Further information at www.uni-mainz.de/eng}

^{Boehringer Ingelheim Foundation}

^{The Boehringer Ingelheim Foundation is an independent, non-profit organization that is committed to the promotion of the medical, biological, chemical, and pharmaceutical sciences. It was established in 1977 by Hubertus Liebrecht (1931–1991), a member of the shareholder family of the Boehringer Ingelheim company. Through its Perspectives Programme Plus 3 and its Exploration Grants, the Foundation supports independent junior group leaders. It also endows the international Heinrich Wieland Prize, as well as awards for up-and-coming scientists in Germany. In addition, the Foundation funds institutional projects in Germany, such as the Institute of Molecular Biology (IMB), the department of life sciences at the University of Mainz, and the European Molecular Biology Laboratory (EMBL) in Heidelberg. www.bistiftung.de}

^{Press contact for further information}

^{Dr Ralf Dahm, Director of Scientific Management, Institute of Molecular Biology gGmbH (IMB), Ackermannweg 4, 55128 Mainz, Germany. Phone: +49 (0) 6131 39 21455, Email: press(at)imb.de}