On editing the genetic code

Edward Lemke, group leader at EMBL Heidelberg, shares his experience as editor of a special issue of ChemBioChem, on the rising field of genetic code expansion.

Explosion on gene motif
The field of genetic code expansion is exploding. IMAGE: EMBL/Manuela Beck, Gemma Estrada Girona, Edward A Lemke & Petra Riedinger. Background image: iStock.com/Soubrette

This special issue is titled ‘Exploding genetic code’ – where did the idea come from? And what does the phrase mean?

In a simple view, DNA is the blueprint for all the proteins that ultimately form the molecular machinery of any living system. This is thanks to the genetic code, in which sequences of DNA correspond to each of the amino acids that make up a protein. The special issue I edited is focused on a set of approaches that many researchers know as ‘genetic code expansion technology’. In genetic code expansion, the natural set of amino acids is dramatically extended. Thanks to this field, scientists nowadays can choose from a plethora of custom designed, so-called ‘non-canonical amino acids’ that can replace a specific amino acid or site in a protein of choice in living cells or organisms. The word ‘explosion’ in this context should be clearly understood in a positive way as a word to describe that the field is expanding at a dramatic pace. Even five years ago, it would have been much harder to put an issue like this together.

It is just a tremendously creative field, with lots of room for innovative ideas and seemingly unconventional approaches.

It is clear that this field has seen a boom in recent years. What drove this expansion?

There are many reasons for this dramatic expansion. Certainly, the field’s potential is what drives investigators to genetically encode new amino acids with novel functionalities. Genetic code expansion allows us to combine the best of biology with the best of synthetic chemistry, to custom-design protein function. It is just a tremendously creative field, with lots of room for innovative ideas and seemingly unconventional approaches. Instead of thinking about what the current state-of-the-art in protein design permits, people can now also approach this the other way around: What do I want my protein to be able to do? Then one inspects what the chemistry toolbox – which originally may have been designed for a totally different, often completely non-biological purpose – offers, and genetic code expansion might be able to deliver a novel tool for biosciences. This is actually how I got into this field. Almost a decade ago, I just wanted to be able to visualise proteins at the single molecule level with high resolution, in order to better study molecular mechanisms. Genetic code expansion turned out to be the method of choice for us, things started working, and now it’s an ideal platform to design better tools for our research.

Another point is that, originally, the technology was cumbersome to apply, but recent advances have greatly simplified this and made the technology robust. Once a technology becomes robust, the demand increases, and more investigators will invest into this area. Nowadays, a single manuscript might already present several novel amino acids at once, and several of those papers are published per year. Meanwhile, innovations are not only driven by developer labs anymore, but now also by people that have a specific application in mind.

What are some of those possible applications?

Well, the huge diversity of proteins and protein function in living things is achieved with basically a set of 20 naturally occurring amino acids. So, with a few hundred more choices of amino acids, the possibilities seem endless. The applications – and since this is still a young field, ‘the application potential’ – range from basic research in the life sciences to drug development, energy science and materials science. Even though this issue turned out pretty thick, it still cannot cover all areas where the technology has an impact, but I think the 20 articles we included cover an impressive spectrum. A few prominent examples are the ability to use light to control protein function in living cells, the coupling of probes to make proteins visible, or the design of better and more stable proteins. The latter is a topic of great health relevance, since many blockbuster cancer therapeutics are protein-based drugs, but are hampered by limited stability patients’ blood – a key issue which can be addressed using these modern protein engineering tools.

I just got the idea at some point and felt the time is right

How did you come to be the editor for this issue?

There are many reviews in this field, but a special issue is an opportunity to bundle the actual state-of-the-art of the technology with a majority of primary research articles. However, a special issue needs a critical mass of exciting stories to be published. I just got the idea at some point and felt the time is right, since I noticed the dramatic increase in interest in the technology, and the number of applications by labs that just got the material from developers. So I discussed the idea with the senior editorial team at ChemBiochem, who immediately endorsed the project. Most of the articles included in the issue are research articles, and as is the nature of things, not all investigators active in the field had a suitable story ready by the time the issue had to go to print – the issue was timed to coincide with the EMBO Chemical Biology meeting 2014, one of the largest conferences in Chemical Biology.

Turning to the editorial process itself, what kind of articles are included in this issue? How did you choose them? Was it difficult to make those choices?

This step was based purely on the scientific quality of each article, and that the article describes an application, new development or a better understanding of genetic code expansion technology. The professional editors from ChemBioChem have a lot of experience with handling manuscripts in this field, and this simplified things. All manuscripts submitted for this special issue were subject to the same procedure (anonymous peer review, and so on) as all other manuscripts handled by ChemBioChem.

Usually as a scientist you’re on the submitting side of the editorial process. What did it feel like to cross camps?

As an author, I was curious to learn how the editorial side might feel. Clearly, I like doing research way too much, so I would not consider becoming a fulltime professional editor. However, the freedom of being a scientist allows us to also explore this direction, for example by being a guest editor, which is only a part-time commitment. This was a very valuable training and a fun experience, and I certainly could think of doing this or a similar task again.

What was the most enjoyable aspect of this experience?

I liked editorial work, and learned a lot about how professional editorial work is carried out and what is involved in order to get a whole issue together. And effectively, the ChemBioChem editors still did most of the work, so this was really much more of a positive experience than anything else.

Finally, could you share something you’ve learned (scientifically or personally) during this process?

Being an independent group leader is probably the best job I can personally think of for myself. If you get an idea, want to do learn something new, or crave for a new experience, such as an editing opportunity, you just need to take the initiative, get a few people interested, and if it benefits science, then there will be a way to do it.

Tags: biochemistry, chemical biology, heidelberg, interdisciplinary, methods, protein synthesis, synthetic biology


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