Prof. Ivan Matić joins the FLI to Lead a New Research Group.

In the following interview, Prof. Matić discusses his decision to relocate to Jena, his long-term scientific vision, and his plans for building a collaborative research group and expanding technological capabilities at the FLI.

Prof. Matić, welcome to the FLI: What motivated you to move from Cologne to Jena and establish your research group at the FLI?

I was attracted to the FLI because it provides an exceptional environment and world-class resources for studying, at the molecular level, the signalling pathways implicated in aging. My research sits at the interface of DNA damage signalling, protein modifications, proteomics, chemical biology and cell biology, and the FLI brings together expertise across many of these areas, as well as other complementary fields, further strengthened by its outstanding core facilities. Establishing my own group here gives me the opportunity to build a research program around PARP1 signalling and its role in genome maintenance and aging, while collaborating with scientists approaching aging from very different perspectives. Jena also offers a remarkably vibrant and collaborative scientific community, with complementary expertise across the FLI and the wider Jena research community. For me, this combination of scientific opportunities, interdisciplinarity and the possibility to build a well-resourced, independent research programme made the FLI a very compelling place to start this next phase of my career.

Looking back at your career so far, what led you to focus on the biology of aging?

My interest in aging developed from a more fundamental fascination with how signalling pathways use post-translational modifications to respond to cellular stress, including DNA damage. During my postdoctoral research in Scotland, I became interested in ADP-ribosylation by PARP1, a signalling enzyme that plays a central role in sensing DNA damage and coordinating its repair. What initially attracted me was the complexity of these mechanisms: upon DNA damage, PARP1 generates a variety of ADP-ribosylation signals, some of which were still awaiting discovery at the time, that can profoundly alter the behavior of proteins and cellular processes. This led me to a broader question: what happens to these protective mechanisms over the course of an organism’s lifetime? PARP1 uses NAD⁺ as a substrate, and excessive or prolonged PARP1 activation in response to severe or persistent DNA damage can consume substantial amounts of NAD⁺, contributing to cellular metabolic stress and, under extreme conditions, cell death. At the same time, studies of exceptionally long-lived organisms and centenarians have highlighted the importance of maintaining genome integrity and efficient DNA repair for healthy longevity. This duality fascinated me: PARP1 is both an essential component of the machinery that protects the genome and a major consumer of NAD⁺. I became interested in aging as a way of understanding how this critical enzyme balances these two functions over the course of a lifetime.

Could you give us an overview of your research and the key questions your group is trying to answer?

Our research focuses on understanding the molecular mechanisms of the DNA damage response and aging by elucidating the role of PARP1 signalling in these biological processes. We are particularly interested in understanding the molecular language of ADP-ribosylation: which proteins are modified, where and with what type of modification, and how these signals change the behavior of the cell. We want to understand how ADP-ribosylation signaling regulates DNA repair and other cellular processes, and how changes in these pathways contribute to aging and age-related disease. To drive these fundamental discoveries, technological innovation is a cornerstone of our work. ADP-ribosylation is a highly complex and technically challenging post-translational modification to study, which has historically left many aspects of its signalling pathways elusive. Importantly, our technological foundation builds on our discovery of serine ADP-ribosylation and its development into a versatile technology platform. Over the years, this has enabled us to develop diverse tools to detect and characterize these modifications with high precision.

What is currently one of the biggest unanswered questions in aging research?

One of the biggest unanswered questions is: could improving the way cells detect and repair damaged DNA actually slow aging and extend healthy lifespan? This is a particularly intriguing possibility given evidence that exceptionally long-lived organisms can possess highly effective mechanisms for maintaining genome integrity and repairing DNA damage. Understanding the relationship between DNA repair, aging and PARP1 signalling is one of the questions I find particularly exciting. Further decoding PARP1 signalling at the molecular level could reveal new ways to modulate its activity safely and selectively, with the ultimate goal of enhancing genome maintenance without disrupting the many other functions of this important signalling pathway.

What methods does your team use to investigate these mechanisms?

We combine biochemistry, proteomics, chemical biology, protein engineering and cell biology. The transformation of our fundamental discovery of serine ADP-ribosylation into a versatile technology platform has enabled us to develop a range of molecular tools that drive fundamental discoveries both in our own lab and across the wider scientific community. At the molecular level, we reconstitute and biochemically characterize ADP-ribosylation reactions to understand how enzymes such as PARP1 generate and regulate these signals. In parallel, we use advanced proteomics to identify modified proteins in their cellular context and precisely map the sites of modification. A major strength of this multifaceted toolkit is that we can move between different levels of biology — from understanding the chemistry of a modification, to identifying its molecular targets, to defining its functional consequences in living cells and organisms.

What kinds of collaborations would you particularly like to develop at the FLI?

I am particularly interested in collaborations that allow us to connect molecular mechanisms with ageing phenotypes at the cellular and organismal level. My group brings strong expertise in ADP-ribosylation, biochemistry and proteomics, and I would like to combine this with complementary expertise in animal models, in particular the turquoise killifish, which is a key model organism for aging research at the FLI. I am also very interested in collaborations within the broader Jena research community, particularly where different technological approaches can be combined to address questions that would be difficult to tackle from a single discipline. For example, I would be interested in integrating our group’s expertise into the Balance of the Microverse Cluster of Excellence, where advanced proteomics could be applied to the analysis of microbial communities. At the same time, I would like my group to contribute our own technologies and molecular tools for studying ADP-ribosylation to collaborative projects across the FLI.

What kind of research culture would you like to create within your new group?

I would like to create a research culture that combines scientific ambition with openness and collaboration. I want people in the group to feel encouraged to challenge established ideas and pursue unexpected observations.  Because our research is highly interdisciplinary, I also want the group to be a place where people with different expertise learn from one another. Someone working on proteomics should be able to understand the biological question behind an experiment, while someone studying cell biology should feel comfortable engaging with the underlying biochemistry. Finally, I want to build an environment in which people can develop as independent scientists. My goal is not only to produce good science, but to help members of the group develop the confidence, creativity and expertise they need to thrive. Whether they choose to pursue careers in academia or industry, I want them to leave the lab fully equipped to take on leading roles.

Do you think aging can be slowed, halted, or even reversed? What does current research tell us about this?

I think the evidence increasingly suggests that aspects of aging are modifiable, but we are still far from being able to simply stop or reverse aging in humans. Research in many experimental organisms has shown that interventions affecting processes such as nutrient sensing, cellular stress responses and genome maintenance can extend healthy lifespan and, in some cases, partially restore aspects of cellular function. The more immediate goal should be to extend healthspan — the period of life during which we remain healthy and functional — rather than simply focusing on lifespan. What I find particularly interesting is the growing realization that aging is not simply a passive accumulation of damage. Cells actively respond to damage and stress, and some of these responses remain remarkably plastic. The challenge is to understand which mechanisms can safely be manipulated to preserve cellular function without creating new problems. This is precisely why I consider it so important to first elucidate these fundamental molecular pathways. Only by understanding at the molecular level how cells maintain their integrity can we develop rational, targeted strategies to help them sustain it.

If we speak again in five years, what would you hope to have achieved with your group at the FLI?

In five years, I would like my research group to have established a clear molecular understanding of how PARP1-dependent ADP-ribosylation contributes to the maintenance of genome integrity during aging. I hope we will have identified previously unknown regulatory mechanisms and molecular targets and determined which of these mechanisms are important for maintaining healthy cellular function. To drive these fundamental discoveries, I would like the group to have developed powerful proteomic methodologies and biochemical tools by expanding our serine ADP-ribosylation technology platform. Ideally, these new tools would be useful beyond our own research and become broadly adopted by the wider scientific community, playing a central role in our technology-transfer efforts. Most importantly, I would like to have built a vibrant and creative research team at the FLI, with a reputation for combining fundamental mechanistic biology with innovative technology development to produce impactful science. If, after five years, we have both changed how people think about PARP1 signalling in aging and provided the field with new ways to investigate it, I would consider that a very successful start.