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Paco Barona Gomez ready to work in Leiden: ‘Fundamental research creates opportunities’

Paco Barona Gomez is the newest associate professor at the Institute of Biology Leiden (IBL). The Mexican researcher is fascinated by the evolution of natural products: compounds made by microbes, but also plants and animals. ‘It’s like we investigate chemical dark matter.’

Why are natural products so exciting to you?

‘Since my PhD, I have been linked to genomics: research on what a particular part of the DNA is for. Genes are made of DNA. They can code for a natural product, such as an antibiotic. To me, it is fascinating to understand why microbes – bacteria and other microscopic organisms – produce these natural products. Because if you look at evolution, there must be a very powerful and long-term reason for that selection to take place. So I got obsessed by this question. What is the reason of existence of certain compounds encoded in the genome?’

Barona Gomez (left) with his students.

How do you investigate that?

‘We try to test our hypothesis of how things have happened. We identify DNA strands, and do experiments to see how they change over time. It is a high risk, high reward method. There isn’t a label with ‘I do this for this particular function’. Each time, we start from an almost blind prediction in a vast universe of DNA. It is like we investigate chemical dark matter encoded by genes.
However, we did find some very promising results. And without realising, we developed genome mining tools. That are algorithms with which researchers can focus their search for a trait in the DNA. For instance, if interested in antibiotic discovery, it can be used that tool to see if there are DNA strands that might be responsible for producing the corresponding trait.’

Are you happy that your developed algorithms have this application as well?

‘Of course. Even though I do think that understanding the underlying mechanisms is most important. A lot of researchers try to solve problems, but applications tend to be hampered due to a lack of understanding. Still, I don’t want to send the message that I am an evolutionary chemical biologist that only is thinking about my own interests. My research has created a few start-up companies, for example. However, I believe that the focus must always be on the ‘why’, instead of how something can be used.’

The blackened cycads recover quickly, probably because of their microbiome.

What research will you focus on in Leiden?

‘We, that is me and a few of my PhD students that will move with me from Mexico, are most interested in further understanding the evolution of natural products. And we want to explore another component that drives evolution: population genomics. We will look how genetic variability influences the evolution of natural products. This seems to be very interesting, as normally in populations, traits are driven to one fixed state. The ‘survival of the fittest’. However, when we look at our model organism, the bacteria Streptomyces coelicolor, evolution is selecting chemical diversity. So you come across a large collection of these natural compounds, not only one, for some reason that we don’t yet understand.’

Baronza Gomez in the rain forest.

But you do already have a hypothesis?

‘A typical solution would be that the chemical diversity is the way to keep alive multiple solutions. The production of some of these natural compounds is very toxic. But once it evolves into mechanisms that are too complicated and toxic, this strand can be removed from the population without killing the whole population.’

Does this also contribute why you chose to come to Leiden?

‘In Leiden you can work together with someone from the plant and animal clusters, for starters. And it is also very nice to be surrounded by a critical mass of microbiologists, which is quite unique. For instance, we have already started collaborating with the Hortus Botanicus and many computational biologists. There is a nice combination between multiple systems, which is broad biology-wise but with very strong expertise. The vision here is the right one, and I look forward to contribute to that.’

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