Faculty interview with Ivan Dikic

Ivan Dikic, PhD

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I’m Ivan Dikic, and this is why I research.

Ivan Dikic is Director of the Institute of Biochemistry II (IBC2) at Goethe University’s Medical School in Frankfurt. He was recruited to the IBC2 in 2002 as a professor and was appointed as its chair in 2009. He was also founding director of the Buchmann Institute for Molecular Life Sciences at Goethe University, where he continues to sustain an outstation lab. Ivan Dikic was trained as a medical doctor in Zagreb (Croatia) and obtained his PhD with Joseph Schlessinger at the New York University Medical Center. He is speaker of two collaborative research networks on selective autophagy (SFB 1177) and ubiquitin networks (LOEWE Ub-Net), and board member of the Cluster of Excellence Macromolecular Complexes (CEF-MC).

Ivan explores molecular mechanisms of cellular signaling and one of his current major interests lies in selective autophagy. His team has provided important mechanistic insight in the regulatory networks and the structures controlling mitophagy, xenophagy and ER-phagy, shaping host-pathogen interactions and impacting on the development of neurodegenerative diseases like ALS.


Ivan Dikic PhD quote

Would you tell us what sparked your interest in basic science?

My father was a veterinarian, and he often allowed me to accompany him to his work. I was fascinated watching him, and this sparked a deeper interest in biology and also pathophysiology. Studying medicine therefore was a natural decision after I graduated from high school. However, as a young medic, I very soon started to feel unsatisfied with the limits of knowledge. I wished to fully understand the molecular causes of disease. I embarked on a PhD in molecular biology in Joseph Schlessinger’s lab at New York University, a decision which proved to be a turning point in my career.


Your research has helped characterize the function of ubiquitin in cellular signaling pathways. To you, what important questions in this area are left unanswered?

We have only just started to understand the versatility of the system and how it functions on the molecular scale. Many areas are completely unexplored and the field still holds surprises. For example, we were one of the pioneering groups in the past 12 months who together unraveled a completely novel mechanism of ubiquitination. Nobody would have ever expected this to exist. We do not know yet what role this mechanism may play in humans, but it for sure is used by bacteria to their own advantage.

Apart from truly exciting discoveries, I do believe that the ubiquitin system still holds a big promise for advancing targeted therapies in many areas of disease


You have made important discoveries in selective autophagy, DNA repair, and innate immunity. Is there one particular experiment or discovery you feel most proud of? An ‘aha moment’?

Looking back on several decades of basic research now, there was surely more than one of these moments. Last summer for example, I saw the beautiful gels produced by my postdoc Sagar Bhogaraju which proved our hypothesis on the novel mechanism of serine ubiquitination via prior phosphoribosylation of ubiquitin (see the answer to question #2). A similar unforgettable moment happened shortly after establishing my lab at Goethe University Frankfurt. We tried to develop a robust assay to prove how ubiquitin is involved in numerous cellular signaling pathways. When we obtained the first results of the yeast two-hybrid screen and identified more than 60 novel ubiquitin binding proteins, I knew immediately that this was a groundbreaking discovery.


Ivan Dikic lab

It is fascinating how ubiquitination is involved in autophagy cargo recognition. Tell me more about what led you to this research and why you were initially interested in studying selective autophagy.

In the 2000s, more and more molecular details about selective autophagy emerged. Having been in the ubiquitin field for a long time, the striking similarity between the two systems obviously caught my interest, and even more so when it became clear that dysregulated autophagy may be involved in the etiology of a broad range of diseases and may modulate therapeutic responses. I was finally pulled in deeply when we were among the groups who identified that autophagy receptors contain both LC3 and ubiquitin binding regions and we started to unravel the molecular events leading to autophagosomal capture of ubiquitinated substrates.


Tell us more about the questions your lab is currently investigating and where you see your research moving in the future?

Recognizing the importance of ubiquitin signaling in pathogen defense and the multiple mechanisms by which pathogens exploit the human ubiquitin system to their own advantage, we have set up an ambitious research program on dissecting and targeting ubiquitin networks in the course of bacterial infections. Very recently, I have received an ERC Advanced Grant which will support this program with 2.5 M € for the next 5 years.

The second important focus of my research continues to be the understanding of the role of ubiquitin in many diseases. Lately, we found exciting links between ubiquitin signaling, autophagy and neurodegeneration, e.g. we have contributed to the discovery of the first susceptibility gene for ALS, and we will surely explore this in much more detail.


Describe why your research is important to the ordinary citizen.

The answer to this is very simple: If we wish to significantly advance medicine, we need to understand the molecular mechanisms underlying diseases and modulate the therapeutic response. Nowadays, a Fleming-type discovery of penicillin by pure serendipity is more than unlikely, and the development of innovative treatments needs knowledge-driven approaches. This is especially true for the field of antibiotics, where we face a global threat caused by multi-resistant pathogens. And this is where we come in with our keen interest in deciphering the molecular mechanisms causing und progressing diseases.


Outside of molecular oncology and cellular signaling, what research do you find especially exciting right now?

Having lived in Silicon Valley for a year now, I am fascinated by the ease and speed of introducing cutting-edge technologies in everyday life. The mentality of “everything is possible” clearly has some roots within the young generation in the San Francisco area. On the professional side, I have been experiencing first-hand how a cross-breed can be established between biology and physics, or more precisely between computing, nanotechnology and informatics. There are multiple institutes where biologists, physicists, mathematicians and chemists work side-by-side and their work synergy is fascinating. To address today’s major questions in biomedicine, we will need multidisciplinary big scale teams.


Do you have any advice for someone interested in a tenure track (TT) position?

Trust yourself, build a good network, find your niche, and actively drive forward your ambitions. Academic science is a tough business nowadays, and the number of suitable candidates by far outnumbers the number of TT positions. Successful scientists in academia are in many senses multi-talents. Take trust, for example. I have seen many early-stage scientists who are the most brilliant brains, but don’t trust their own data. But in the end, timing is everything, and tying a story up at the right moment is essential. Don’t get me wrong, quality of data needs to be above anything else, but if data is never critically discussed with peers, there can be no scientific progress. This is why a good mentor is almost essential, someone who is experienced enough to recognize excellent quality data and supports an early-career scientist in building networks, defining promising new directions and – most importantly – publish the highest quality and original data first.

Along these lines, I would also stress that today it is becoming less an imperative to publish only in selected top journals. Leading scientists are rather starting to emphasize that the quality of science is the most important parameter in future promotions and tenure decisions.


And finally, if you could have one superpower, what superpower would that be?

Considering my current lifestyle, I would probably benefit the most if I had the power to stay awake 24/7/365 a year. I enjoy tremendously this sabbatical year in San Francisco and living in Palo Alto. I have so many new ideas and plans in science but wish to also spend time with my family while we are here. So having more time to enjoy science and be privately happy would be on the top of my wish list.



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