Blog 25

Introduction

Molecules is as old as MDPI, beginning in tandem with Molecular Diversity Preservation International (as MDPI was known back then) to promote and preserve chemical compounds. The journal is the cradle from which the MDPI we know today would emerge. Its founding principles were commitments to the preservation of diversity and accessibility. A quarter of a century later these values have shaped MDPI as the Multidisciplinary Publishing Institute and now find themselves applied not just to the chemical samples recorded in Molecules but to every aspect of MDPI’s work and the 331 peer-reviewed journals that we publish—so more than a little diversity!

As well as being the seed for MDPI as a publisher, Molecules has itself flowered into a journal that has published almost 30,000 articles since its inception in 1996. So what does it take to spearhead the journal that kicked off an Open Access powerhouse? We spoke to Section Associate Editor Dr. Steven Verhelst to find out. There’s a wealth of events going on to celebrate the 25th Anniversary of Molecules’ creation, including Anniversary Special Issues, a Best Paper Award and expansion of the Editorial Board. However, molecules are nothing without their chemists and Molecules and MDPI would be nothing without the work of Dr Verhelst and his colleagues. This is the closest you’ll get to molecular chemistry without a labcoat and goggles!

1. Could you introduce yourself for us?

I was born in a small town close to Rotterdam in The Netherlands. In highschool I had broad interests—mathematics, physics, chemistry, biology, literature, art. I chose to study chemistry at Leiden University, where there was lots of attention on the practical aspects of chemical research. At the moment, I am an associate professor of chemical biology at KU Leuven in Belgium and a group leader in chemical proteomics at the Leibniz Institute for Analytical Sciences ISAS in Dortmund, Germany. Besides chemistry and chemical biology, I also enjoy reading, creative writing, listening to heavy metal, (molecular) cooking and watching movies (especially those of the Coen brothers, Paul Verhoeven and Quentin Tarantino).

2. Can you tell us a little about your own career as a scientist?

I enjoyed my studies in chemistry a lot—especially the organic chemistry part. The lectures from Prof. Gijs van der Marel, Prof. Arne van der Gen, Prof. Jacques van Boom, Prof. Jan Cornelisse and Prof. Johan Lugtenburg made a lasting impression. I therefore decided to do my nine-month MSc thesis work in the Bioorganic Synthesis group of Prof. Van Boom.

What has been really decisive for my career path is my second undergraduate internship at the Department of Immunology of the Harvard Medical School, in the laboratory of Prof. Hidde Ploegh. Here, I combined organic synthesis with biochemistry and cell culture experiments, and I also met my future post-doc advisor Matt Bogyo.

In 1999, I returned to Leiden University to pursue a PhD in bioorganic synthesis, because I wanted to master how to synthesize complex molecules. After my PhD, on the topic of aminoglycoside antibiotics and their interaction with RNA, I moved to Stanford University to do a post-doc in chemical biology. Here, I learned never to be afraid to learn new techniques. Although I still did quite a lot of synthesis, I also performed radioactive labeling experiments, biochemistry, cell culture, protein expression, proteomics and some in vivo work with zebrafish larvae. My post-doc advisor Matt Bogyo was very inspiring, showing me how you can do good science and also enjoy work and life.

After a few years of post-doc, it became clear that I had too many ideas for my own two hands to perform, and I started to apply for faculty positions and career development awards. By the end of 2007, I had several options in the USA and Germany. With the funding situation in the USA being very poor, I decided to accept the Emmy Noether career development award of the German Research Foundation DFG and I moved to the Technical University Munich as an Emmy Noether & TUM junior fellow. This award covered a five-year period and the benefit was that I did not need to worry about funding very much. I also got great support from Prof. Dieter Langosch, the chair of Chemistry of Biopolymers, to which my research group was affiliated.

In 2014, I received another DFG grant and moved to the Leibniz Institute for Analytical Sciences, headed by Prof. Albert Sickmann. I still have a co-affiliation to this institute and run a small group there but, in 2016, I moved to Leuven as associate professor in Chemical Biology. I received tenure in the fall of 2017 and joined as a member of the departmental board in the fall of 2020.

3. Your research focuses on a pivotal area of covalent chemical probes, targeting mainly proteases . Why is it so important and how it may affect humankind?

It must have been at the lab of Hidde Ploegh back in 1998 that I became fascinated with proteases. Proteases are proteins that cleave other proteins and, if you think about this for a bit longer, this is quite special. Proteins are builders and building material. But if proteases are around that break down proteins, why do I exist? The existence of proteases themselves already implies a high level of activity regulation. If something goes wrong with this regulation, a disease may develop.

By developing and applying small molecules termed activity-based probes, my lab tries to obtain more knowledge about the biomedical role of certain proteases and pinpoint them as future targets for drugs or diagnostics.

4. Could you give us an example of a paper that changed your outlook on your field?

I would name 2:

Activity-based Protein Profiling: The Serine Hydrolases

Epoxide Electrophiles as Activity-Dependent Cysteine Protease Profiling and Discovery tools

These two papers by the groups of Benjamin Cravatt and Matt Bogyo started the field of activity-based protein profiling, a field that I have worked in for almost two decades now.

5. What encouraged you to take up the position of Section Associate Editor and when it started?

I’ve just taken up the position of Section Associate Editor at the beginning of 2021, after being invited by the Section Editor-in-Chief Roland Pieters.

6. Are there improvements that you would like to see in the future in Molecules, and specifically in the Chemical Biology Section?

I see quite some good reviews and good papers appearing in the chemical biology section of Molecules. As in any journal, quality still varies. Molecules has a steadily increasing impact factor, and this almost automatically goes hand-in-hand with a higher rejection rate. Sometimes, tough decisions may need to be made, especially when conflicting referee reports are returned. This may mean overruling referees recommendations (either in favor or disfavor of the authors).

7. Do you have any advice for early-stage researchers?

At the early stage of your career (PhD student, post-doc): (1) choose a good advisor that supports people in the lab. (2) Choose a project that you like, especially the day-to-day experimental work. Success is built on failure, and most experiments will fail. Your success comes from the few experiments that work and from recognizing the strange results in failed experiments that may tell you something meaningful. Your joy, however, will not only come from success, but also from the pleasure of doing experiments. Therefore: enjoy the day-to-day work and live in that moment. Once in a while, I still do experiments—although it’s way too little. But if I am in the lab and I put on a Slayer album as background music, I can even enjoy running silica column chromatography.

At an early stage of your career as a principle investigator: (1) create a nice lab atmosphere, in which people feel well. (2) Don’t micromanage. Allow people to make mistakes. (3) Do (part-time) labwork for as long as you can. In a small lab, you can lead by example: how to set up experiments efficiently, how to deal with failed experiments, how to troubleshoot. And you can get a lot done, even if you spent only part of your day in the lab. For the some of the first research papers from my lab, I have performed most of the synthetic work. Doing experiments in the lab also reminds you that things do not always work out as planned.

Thank you very much for chatting with us Dr. Verhelst. It seems that even when studying the fundamentals of human life, it’s still important to enjoy the fundamentals of science and research. Just as a lot has changed since Dr. Verhelst began his scientific career at Leiden University, MDPI and Molecules have both drastically evolved in the last 25 years but what I’ll take from this interview is that, as we continually strive for bigger and better things, we musn’t forget where and why we began.