You’ve worked with nucleic acids, such as DNA and RNA, your whole career. What is it about these molecules that interest you so much?
What I find fascinating is that it's only four building blocks in DNA and RNA which have such diverse functions in all our cells—from transport of genetic information and regulatory functions to catalytic functions. That's really cool.
What we achieved now is that we can incorporate artificial building blocks into RNA at specific positions. We can do this enzymatically through an in vitro transcription reaction from a DNA template into the RNA of any length. That bit is really important because many of the regulatory, non-coding RNA molecules, which are RNA molecules that are not coding for proteins, are between several hundreds to several thousand nucleotides in length. So it’s crucial to have access to modify such large molecules and be able to mark them with reporter groups at desired positions to visualise them, to look at distributions, where they are transported inside the cell and to get an idea of their function.
So we’re at an early but really exciting stage.
When you mention these artificial building blocks, are you referring to introducing new base pairs and extending the genetic alphabet beyond nature’s adenine-thymine and guanine-cytosine pairs?
At the moment, we can enzymatically incorporate one new type of an artificial base pair. It’s called a hydrophobic base pair, consisting of two heterocycles which can adopt a Watson-Crick shape. They do not bond through a hydrogen bond, it’s shape complementarity and hydrophobic effects which hold them together in the duplex. The base pair can be replicated in DNA, and we can also transcribe it into RNA.
What I dream of is to be able to use an expanded genetic alphabet as a toolbox to develop functional molecules in five to ten years. To be able to do in vitro evolution of nucleic acids to find nucleic acids which have new functions, and to do this with an expanded genetic alphabet.
This would allow us to evolve nucleic acids which, for example, catalyse carbon-carbon bond formation or other catalytic transformations, unusual for nucleic acid catalysis. In a couple of years, I hope that we are at a point where we can basically tailor-make nucleic acids with specific catalytic functions.
That’s fascinating. Seeing as you have been in this field your whole career, if you look back on your publications, which do you think is your personal favourite?
I think my favourite publication is one I did with Professor David Lilley at the University of Dundee, with whom I did my postdoc. This work was about the catalytic mechanism of the hairpin ribozyme which we published in JACS in 2012. That dug really deep into how a small catalytic RNA, the hairpin ribozyme, actually catalyses a reaction, specifically the cleavage of the phosphodiester bond [in the RNA backbone, editor’s note]. It showed how this actually works in detail, and I found that very exciting—so I think that would be my favourite.
Did you always know that this was the field you wanted to go into? Did you have mentors encouraging you along the way?
I was always interested in chemistry and biochemistry, or what we would call chemical biology now. When I started my studies, I didn’t know much about the different areas that you could go into but I have always known that I was interested in the chemical background of biological systems. I enjoyed my studies and realised, when I did research for the first time for my bachelor thesis, ‘oh, this is how you work in a lab, this is how you do research.’ That was a whole new experience for me and I discovered that I really liked nucleic acid chemistry.
I think I was very lucky to have help during my career, especially during my studies, from mentors. My PhD supervisor, Thomas Carell at LMU Munich, was extremely supportive and sent me at an early stage to conferences to get a taste of the scientific world. He involved his co-workers in every step of writing manuscripts, publishing and so on. I would also say that, later on, to get a faculty position, you need, besides your scientific reputation, a portion of luck as well—you need to be there at the right time with the right topic.
In November, as you may know, AcademiaNet celebrated its ten year anniversary and we have spent some time looking back over the last decade. Do you feel optimistic about the future in terms of the further inclusion and prosperity of women at academic institutions?
I feel really positive, there is a lot changing right now and a lot has changed in the last ten years. I think women are more visible and getting more promotion. And people are aware of the problems that still exist—also for me.
For example the ongoing question for many female scientists, can you have kids during your qualification phases? I have four kids now and my oldest is five, he was born two years after starting my own lab. I get a lot of support from my partner and family, and I feel having both, kids and an academic career, has become more accepted. It all depends on the support that women receive so they don’t have to choose between children and an academic career.
You also have to find the right institutional ‘setting’ and that is something which has changed in many institutions which are establishing a family-friendly work environment. That’s great because it’s always the same issue: when you start your own independent work, you’re usually at an age when, if you haven’t got and you want kids, that’s the time when you will have them. That’s still a major problem, but I think it is getting better as people are in general more aware of it.
That’s a wonderfully hopeful note to end on. Professor Kath-Schorr, thanks very much for your time.(© Emilie Steinmark / AcademiaNet / Spektrum.de)