Inaugural lecture Martin Giera | “If we understand these networks well enough, we may be able to influence them in a targeted

What is the key message of your inaugural lecture, and why did you choose this topic?

“The main message is that everything is intertwined. This is true for biology, where genes, proteins and small molecules, metabolites, constantly influence each other, but also for science and society themselves. My personal interest mainly lies in metabolism: all the chemical processes that keep our cells and bodies functioning. When I started my scientific journey, we used to think of many metabolites mainly as fuel, building blocks or waste products. We now know that many of them actively influence biology. I chose this topic because this idea has followed me throughout my scientific career, from my early work on cholesterol metabolism to what we are doing today.”

What are some of the main areas of research that you and your team are currently working on?

“We study metabolism, and especially lipids - in other words, fats and cholesterol. One part of our work is very technical: we develop methods to measure these molecules as comprehensively as possible. The other part is biological. We want to understand what these molecules actually do and how metabolism changes in disease. We are particularly interested in neurodegenerative diseases (e.g., multiple sclerosis and Alzheimer’s disease) and inflammatory diseases (e.g., MASH and sepsis One example is our work on cholesterol metabolism, where we are investigating whether changing the flow of the pathway could be used to protect cells and eventually lead to new treatments.”

What role do education and patient care play in your vision for this field?

“For me these things belong together. We work at a university medical center, so in the end our research should somehow benefit patients. That does not mean that every experiment needs an immediate clinical application. Fundamental research is essential. Education is equally important. I was trained as a pharmacist but eventually chose biochemistry because I simply like to figure things out. I think we should give students that same freedom: teach them the basics, of course, but above all encourage them to think critically, question things and develop their own ideas.”

Is there a particular moment or experience from the past few years that has really stayed with you?

“One thing I find remarkable is that I am now working again on an enzyme called DHCR24 that I first studied during my PhD more than twenty years ago. At the time, I was simply trying to understand cholesterol biosynthesis and develop inhibitors for enzymes in this pathway. However, when I started writing my PhD-thesis, there was this voice in the back of my head telling me: all these biochemical intermediates are not there for nothing, there must be a deeper meaning to these metabolites. With the help of incredible collaborators and friends, this idea matured, became central to my scientific work, and eventually led us to propose this enzyme as a potential therapeutic avenue for inflammatory diseases. Science rarely develops according to plan.”

How can patients and society benefit from or notice the impact of your work?

“Most patients will probably never hear the word metabolomics, and that is fine. What matters is what we can do with it. Metabolism changes when we become ill, and these changes can tell us a great deal about what is happening in the body. If we understand them better, they may help us detect disease, understand why one patient develops differently from another, or identify completely new ways of treating disease. In our own work, for example, we are trying to understand whether manipulating cholesterol metabolism could eventually become a new approach to treating neurodegenerative diseases.”

Looking ahead, where do you hope the field will be in 10 to 15 years?

“We are pretty good at measuring enormous numbers of molecules. In 10 or 15 years, I hope we will be much better at understanding what all these measurements actually mean. How do all these molecules shape biology together? That is the interesting part that will allow us to move beyond using metabolism simply to describe disease. If we understand these networks well enough, we may be able to influence them deliberately and use the body’s own regulatory mechanisms to redirect a diseased system back towards a healthier state.”

Martin Giera’s inaugural lecture ‘Everything is intertwined: Metabolism, life, and the logic of interdependence’ will take place on Friday 4 September 2026, from 16:15 to 17:00, and can be watched live via the livestream on Leiden University’s website.