Günther K.H. Zupanc: Embrace the twists and turns, and never lose sight of your dreams

In the following autobiographical narrative, Günther K.H. Zupanc reflects on his career as a scientist, educator, and writer. His essay is a reminder for students and young scientists that although one’s career path may not always be straightforward it is important to keep following one’s passion.

Formative early years

As far back as I can remember, I have always loved nature, in particular watching animals. When I was 13 years old, I bought my first aquarium to keep the fish and urodeles I had caught in rivers and ponds near my hometown, Augsburg (Germany). Shortly thereafter, I started breeding tropical ornamental fish, such as guppies and cichlids. I was fascinated by their rich behavioral repertoire, including aggressive and reproductive behavior, and their development from egg to adult. I captured their behavior on photographs and Super-8 films, and  built my own underwater microphone to record the sounds they produced during courtship and territorial defense.

At that time, ethology ― the study of natural animal behavior — sparked interest far beyond the scientific community. Its founder, Konrad Lorenz, had just been awarded the Nobel Prize for Medicine or Physiology. Unlike the vast majority of scientists, he was a celebrity who made the covers of popular magazines. Ethological research, particularly the social and psychological implications of its discovery of innate components of behavior, was the subject of what often turned into heated debates.

Although the popularity of ethology was certainly a major factor that drew me into the study of behavior, I also grew dissatisfied the more I read the books and journal articles by ethologists of the Lorenz School. It was their restriction to mostly qualitative descriptions of observations and the frequent lack of rigorous quantitative, experimental analysis that made me feel increasingly uncomfortable.

Fueled by this dissatisfaction, I expanded my readings to publications by behaviorists, such as B.F. Skinner, and those among European and American ethologists who applied the rigor of laboratory conditions to the analysis of behavioral mechanisms. Since most of these papers were written in English, I initially struggled reading them due to my limited proficiency in this foreign language. However, by taking adult evening classes to improve my English, I gradually overcame this difficulty.

One of these ethologists who impressed me deeply was Walter Heiligenberg. A student of Lorenz, he had moved, in 1972, from the Max Planck Institute for Behavioral Physiology in Seewiesen at the outskirts of Munich to the Scripps Institution of Oceanography of the University of California, San Diego (UCSD). His approach to the study of behavior was exactly what I had been looking for: a rigorous quantitative analysis.

Athough I had just turned 15, and I did not receive any help from my high school teachers who told me that I was too young to do research, I started a research project on my own. I set up several fish tanks and a bench for chemical analysis of water samples at my parents’ home. In this project, I studied how the concentration of ammonia affects the aggressive behavior of cichlid fish. Since ammonia is the main excretion product of fish, its concentration in the water reflects population density. Although population density had been known previously to have a major impact on aggression, my early research identified ammonia as an important environmental cue that appears to be used by fish as a proxy to gauge the number of neighboring fish present, thereby regulating the motivation of an individual fish to engage in aggressive encounters. During the next few years, this and other projects earned me a number of awards at science fairs, including first prize in the national competition and second prize in the international competition of the European Contest for Young Scientists and Inventors.

With the national and even international recognition of my early research work, I had no doubt that I would be admitted to college. I was confident that any university would welcome a promising young scientist among its ranks.

However, I was about to learn my first career lesson.

Admission to college for students who wanted to enroll in popular courses, such as medicine or biology, was regulated by the Zentralstelle für die Vergabe von Studienplätzen, a central agency that based its decision mainly on the overall grade received in the Abitur, the graduation qualification of the Gymnasium (a selective type of German secondary school that prepares students for higher education). Since I had been absent from school for significant amounts of time the years before graduation to attend science fairs and visit research institutes (and, admittedly, a good portion of the remaining time I felt better invested in watching the behavior of fish and running experiments than in doing my school homework), my Abitur grade, and particularly my grades in Latin and Ancient Greek, were anything but outstanding. However, the rules of the Zentralstelle permitted exceptions, for example for members of the Olympic teams, who could compensate low grades in the Abitur with their athletic achievements.

Since I had not even contemplated the possibility of a negative decision by the Zentralstelle, its decision letter came as a complete shock to me: I was denied admission to college. My dream of studying biology and pursuing a career as a researcher had abruptly come to an end.

But just after I had learned that even the most reasonable conclusion may not be shared by everyone when it comes to career (and, as I had to add later in my life: funding or publication decisions), I was about to learn lesson number two: at times of seemingly hopelessness, sometimes help is just around the corner.

A local newspaper had reported my misfortune. This article would not have changed the course of events had not a major news agency followed up on this story. Their report was published in virtually every German newspaper and broadcast by radio and TV stations. Although I did not feel comfortable becoming the subject of national headlines, the public outcry did its job. My case was discussed in federal and state parliaments, politicians called for a reform of the college admission process. As a result of this debate, half a dozen universities offered me a place on their biology degree programs.

 

Undergraduate years and first book publications

After I had accepted the offer of the University of Regensburg, the rest of my undergraduate career was more ordinary than its beginning. This time, I played, at least when it came to grades, according to the rules. I graduated with a Diplom, the German equivalent of a master’s degree. My GPA was excellent, and my record included the award of a prestigious fellowship from the Friedrich Ebert Foundation.

The unconventional activities during my undergraduate career were largely restricted to the writing of my first three books. During my Gymnasium years, I had, in addition to research, developed a deep interest in writing articles about various science topics. My articles were published by major German newspapers and magazines, and several of them were translated into other languages and appeared abroad. As formal recognition of this achievements, I received two major awards, the Förderpreis der Kölner Schule Schule — Institut für Publizistik as best popular science writer under the age of 18, and, shortly after I had started college, first price in the Reporter der Wissenschaft competition as best science reporter under the age of 30.

Benefitting from this success, I secured a contract with a publisher to write a popular science book on the behavior of fish. I received half of the agreed royalties before I even had written a single line (unfortunately, this has not been the case in any of my subsequent projects). I used the quite substantial amount of money to travel around the world during summer breaks, interviewed many of the leading fish biologists, and studied fish in their natural habitats in oceans, lakes, and rivers. The book, Fish and Their Behavior, was illustrated in full color, and many of the over 200 figures were done specifically for this project (Zupanc 1982). It was published at the time when I received the German equivalent of a bachelor’s degree. Subsequently, the German original was translated into English (Zupanc 1985, 1988a). With 50,000 copies sold, it became a bestseller in the popular science field.

My second book was a response to my experience as an undergraduate student. I felt that no suitable book was on the market for teaching behavioral biology labs. I, therefore, contacted 18 renowned German behavioral biologists to suggest a book project through which we would develop and disseminate novel ideas on how to teach, based on student-led observations and experiments, such a lab. I coordinated these efforts as Editor, and although I was still an undergraduate student, the book was accepted by the leading German academic publisher in the field, Verlag Paul Parey (Zupanc 1988b). This laboratory manual subsequently became a standard text in the training of biology students at many German universities.

My third book came into being more by accident than design. I was invited to write an article for a biology teacher journal about the use of fish for inquiry-based learning in the classroom. However, the more time I spent writing, the more the manuscript transformed into a comprehensive guide, and finally it was published in form of a book (Zupanc 1990).

My record of academic achievements and extracurricular activities during my undergraduate studies should have been the ticket for a smooth transition to the next stage of my career, a Ph.D., (I use the cautionary qualifier “should” because of career lesson number one I had learned six years earlier). However, I decided not to go down this path. Over the years, my research interest had gradually extended from the study of animal behavior to the exploration of neural mechanisms of behavior. Like the dissatisfaction I had experienced during my teenage years regarding the lack of analytical and quantitative rigor in parts of ethology, I now felt inadequately prepared for entering the field of neurobiology. Reading the biographies of the very best researchers in this field, I noticed that many of them had received their formal training in disciplines other than biology, foremost in physics. So, I decided to go back to college as a freshman for studying physics, instead of immediately applying to grad school.

 

Graduate study and move to the United States

Two years later, now equipped with the equivalent of a bachelor’s degree in physics, I felt ready for the type of research I wanted to pursue. And I was determined to learn the skills necessary for doing this research from the person I still considered to be the best — Walter Heiligenberg. I had interviewed him for my Fish and Their Behavior book, and since then we had stayed in touch. As I had hoped, he invited me to join his lab, and at the same time my application for admission into graduate school at UCSD was successful. So, in 1987, I moved from Germany to the United States to start my graduate career. As it turned out, both of these choices were a perfect match.

Today, I still consider Walter the most dedicated researcher I have ever met. He ran his own physiology experiments every day, from early morning until — quite often — late in the night, interrupted only by a two-hour dinner break. And he did this work with a degree of joy that was simply contagious. On the other hand, Walter and I never had what, at least today, is stipulated as an absolute must in any graduate handbook: formal regular meetings of Ph.D. advisor and advisee. Nevertheless, he was the best mentor I could have dreamed of. I learned from him simply by watching how he ran experiments. And I enjoyed a degree of freedom that no other thesis advisor would have tolerated: I spent endless hours of my time on the beach of La Jolla, where I did most of my readings and writings. Walter also supported me to visit other labs, on campus and abroad, sometimes for weeks at a time, so that I could learn the skills that were not available in his lab but that I needed for my research work.

The model organism studied in Walter’s lab was a weakly electric fish with the scientific name Eigenmannia. He suggested that I find out what morphological changes in specific brain neurons govern seasonal changes in courtship and aggressive behavior. He and several postdoctoral fellows in the lab had identified in this species a brain site called the prepacemaker nucleus that controls chirping, a behavioral pattern that plays an important role the electric communication of this fish. Males and females produce chirps vigorously as part of their courtship behavior, but they hardly ever chirp outside the breeding season. By labeling individual neurons of the prepacemaker nucleus in breeding and non-breeding fish, we discovered that the dendrites of these neurons extend and retract in concert with the environmental changes that govern the transition from non-breeding season to breeding season, and vice versa. When the dendrites extend, they make synaptic contact with sensory neurons that signal the presence of another electric fish. The input provided by these sensory neurons drives the activity of the chirp-controlling prepacemaker nucleus neurons (Zupanc and Heiligenberg 1989; Zupanc 1991). Through this research, we had discovered a phenomenon with wide-reaching implications: that nerve cells in the adult brain exhibit a much higher degree of plasticity than previously assumed, and that such changes in neuronal structure can be used to accommodate long-term alterations in behavior.

With my thesis work, I had found the theme that has defined my research interests ever since: exploration of cellular mechanisms of structural plasticity in the adult central nervous system. I defended my thesis in 1990, in a record-breaking half of the time the average graduate student stayed in the program. In a short of amount of time (which included a subsequent one year as a postdoctoral fellow in the Heiligenberg lab), I authored a total of eight papers.

Perhaps even more important than establishing an excellent record was the freedom Walter gave me. This freedom enabled me to explore new research directions, independent of his own research interests. One of these new directions turned out to be particularly promising. Together with my wife (who was an undergraduate student majoring in microbiology at UCSD), we tried out a novel method to see whether new neurons were generated in the adult brain of teleost fish. This method was based on the incorporation of a molecule with the chemical name 5-bromo-2’-deoxyuridine, or simply BrdU. This molecule, foreign to the body, is incorporated into newly synthesized DNA during mitotic division. DNA with integrated BrdU can then be visualized in tissue sections through immunohistochemical techniques. We were the first who applied this method to study the phenomenon now known as ‘adult neurogenesis’ (Zupanc and Zupanc 1992). Since then, BrdU-labeling has become a standard method, used by hundreds of investigations to identify adult-born cells in the central nervous system.

 

Expanding my scientific interests and becoming a rising principal investigator

Despite this early success, I realized that to make further progress I would need to acquire the skillset and conceptual understanding of a developmental biologist, not just rely on my expertise as a behavioral neurobiologist. So, I declined several offers to join, as a postdoc, laboratories working on topics related to the study of the neurobiology of behavior, including the lab of a principal investigator who shortly thereafter received the Nobel Prize. Notwithstanding my rather limited credentials in developmental biology, I applied for positions in this area. One of my applications was successful. I was offered a junior research group leader position at the Max Planck Institute for Developmental Biology in Tübingen, Germany. To support my research, I received a highly respected Hermann von Helmholtz Fellowship in Neurobiology and, as standard practice of the Max Planck Society, a generous intramural funding package to get my own lab up and running

The institute provided a vibrant research environment, which attracted some of the very best minds from all over the world. Given that I was new to the job of principal investigator, I was lucky that several brillant individuals joined me, including my first Ph.D. student, Thomas Stroh, now a faculty member of McGill University, and Jürgen Soutschek, who subsequently played a key role in the development of RNA interference technologies for silencing genes.

Although I continued to do some work in the area of behavioral neurobiology, including an analysis of chirping behavior in electric fish (Zupanc and Maler 1993) and the development of a novel method to trace neuronal connections in the brain (Zupanc 1998), the main emphasis of our research was on adult neurogenesis. Together with my technician, Ingrid Horschke, I undertook a project that would have been far too ambitious for a graduate student: a quantitative high-resolution mapping of the neurogenic niches in the entire brain. After three years of intensive work, we published the first investigation of its kind in any vertebrate species (Zupanc and Horschke 1995), using the brown ghost knifefish (Apteronotus leptorhynchus) as a newly established model organism to study adult neurogenesis. Our work revealed approximately one hundred such niches, harboring adult stem cells that give rise to an average of 100,000 new cells within any 2-hour period. Both numbers are astonishing, considering that in the adult mammalian brain only two neurogenic niches have been found, and the number of new cells (relative to the total number of brain cells) these niches give rise to is approximately two orders of magnitude lower than in the brain of teleost fish

Jointly with a master’s student, Regina Ott, I was able to link this enormous neurogenic potential to the well-established potential of fish to regenerate brain tissue after injury (Zupanc and Ott 1999). The ability to generate new neurons in response to injury is one reason why fish — in contrast to mammals — can repair brain tissue, often even after extensive lesions caused by trauma.

The other reason, as we demonstrated, is that fish use a special type of cell death called apoptosis to remove damaged cells (Zupanc et al. 1998). Apoptotic cells die in a controlled and clean fashion. Not surprisingly, apoptosis is the predominant type of cells death occurring during embryonic development to eliminate supernumerary cells. By contrast, in mammals most of the cells affected by injury die through necrosis, a type of cell death that is accompanied by inflammation of tissue. In turn, this results in a massive wave of secondary cells death, and thus in much larger tissue damage than caused by the traumatic event alone.

During my five years at the Max Planck Institute, I also obtained the formal qualification for a professorship at German universities, the Habilitation. The credentials for this highest academic degree in Germany are earned in a similar way as assistant professors on tenure-track in the United States qualify for tenure: through research accomplishments and proof of teaching experience. While I established my research record at the Max Planck Institute, I gained my teaching experience through appointment as an adjunct assistant professor at the University of Tübingen. Although I had enjoyed tutoring students and giving lectures to various audiences since my Gymnasium years, I had not taught college courses before I started the Habilitation process. However, I immediately fell in love with this more formal way of teaching. By the time I submitted my dossier for final evaluation, I had taught twice as many credit hours as were required for the Habilitation. The enthusiasm that I developed for teaching was, at least in part, due to my official faculty mentor at the University, Hans-Ulrich Schnitzler. He was a dedicated teacher, whose attitude towards students reflected what he emphasized in his words: even at so-called research universities, teaching should be as important as research. He also helped me to navigate through the sometimes quite complicated evaluation and approval process involved in the Habilitation so that I received my Dr. rer. nat. habil. degree just five years after my Ph.D., compared to the then national average of 11.5 years.

Despite my achievements in both research and teaching, there was a catch: The Habilitation in Germany does not come with tenure. After completion of my contractual five years in Tübingen, I had to look for a new job elsewhere.

 

Teaching at the University of Manchester: the love affair intensifies

I found this new job (including tenure) in England, at the University of Manchester. After my work at two research institutions, the Scripps Institution of Oceanography and the Max Planck Institute for Developmental Biology, it was the first time that my formal duties included teaching, in addition to research. During my five-year tenure at the University of Manchester, I was recipient of several grants from federal sources and non-profit organizations, including the Biotechnology and Biological Sciences Research Council, Royal Society, and Leverhulme Trust. In addition, I received the prestigious Sir Henry Wellcome Commemorative Award for Innovative Research. Supported by these funds, the members of my lab and I were able to further advance our research in the areas of both adult neurogenesis (e.g., Clint and Zupanc 2001; Zupanc et al. 2003) and neuroethology (e.g., Engler et al. 2000; Engler and Zupanc 2001; Côrrea and Zupanc 2002).

I also invested considerable time in several activities for promoting the public understanding of science and for encouraging high school students from socioeconomically underprivileged backgrounds to enroll in college. Since I was the first of my family to attend college, and my father was severely disabled and died shortly after I had started my undergraduate study (prompting the need to support myself), such engagement has been particularly important to me. During my five years in Manchester, every summer, I organized, with the help of the members of my lab, the biology strand of a Higher Education Summer School. This event provided the participating students with the opportunity to observe and analyze the behavior of animals, and to run their own experiments.

Although our research output continued on an upward trajectory, it was perhaps teaching that had the most lasting impact during the five years of my tenure at Manchester. There was a widely shared consensus among faculty of the School of Biological Sciences to promote excellence in teaching and mentoring of students. Inspired by this atmosphere, I designed from scratch two undergraduate courses on behavioral neurobiology. They became highly popular among students. When a commissioning editor of Oxford University Press learned about these courses, she asked me whether I would be interested in writing a textbook on the topic. I agreed. The book was published under the title Behavioral Neurobiology: An Integrative Approach two years after I left Manchester (Zupanc, 2004). Now in its third edition (Zupanc 2019a), it is more frequently adopted for teaching this subject at colleges in the United Kingdom and in the United States than any other text. Ironically, when I myself was a student I never took any class on animal behavior or behavioral neurobiology. Much of what I have learned in these areas is self-taught. I tend to believe that this independent learning has enabled me to maintain a healthy degree of scientific independence, something from which my approaches to both research and teaching seem to benefit.

 

Going global and becoming an active player in major educational reform

My tenure at the University of Manchester was productive, and the interactions with my colleagues were inspiring and friendly. I had, therefore, little intention of leaving this place — except if an extraordinary opportunity were to arise. This call came in a rather unexpected way. Reimar Lüst, one of the most prominent European science managers who had held many high-profile positions, including president of the Max Planck Society, Director General of the European Space Agency, and president of the Alexander von Humboldt Foundation, had campaigned for many years for a reform of higher education in Germany. To ignite the reform process, he proposed the establishment of a new type of university. When his idea became reality, this private institution accommodated a global population of undergraduate and graduate students, offered all courses and exams in English, covered the full spectrum of disciplines in the natural sciences, humanities, and social sciences, carried out excellent research, and supported interdisciplinarity in both research and teaching. Financial support came initially from the Free Hanseatic City of Bremen, which also provided an area with buildings for the campus. The academic infrastructure was set up with the help of Rice University in Houston, Texas, and the state-funded University of Bremen, both of which functioned as partner institutions. What was still needed was an internationally experienced faculty with pioneer spirit. The job description clearly fit my profile, and I could not resist the call — how many people in academia ever have the chance to become an active driver of educational reform on such a scale?

I joined the new university, the International University Bremen, as Full Professor in 2002 and was later elected as Speaker of the Biology Faculty. Our foremost task was to swiftly establish undergraduate and graduate programs, and to define the specific curricula. To our surprise, this task turned out to be easier than what most of us had anticipated. Based on our experience with previous institutions, we knew that even the proposal of rather minor changes to an existing program often results in discussions that drag on forever, and that at the end many faculty members seem to be happiest with a compromise that suspiciously resembles the status quo. Since the constraints of ownership defined by the past did not exist in the foundation stage of the International University Bremen, people were much more open to novel ideas, and the majority of programs (most typically containing elements of both German and U.S. American higher education) were designed within a few weeks or months.

With these new ideas, we were able to attract many outstanding students from all over the world. Within a few years, the university had grown from approximately one hundred to nearly one thousand students, the vast majority of them coming from abroad. A true global university! Our efforts to break new ground in higher education received prominent recognition in 2009 when the Biology Undergraduate Degree Program was ranked top among all the biology programs in Germany, Austria, Switzerland, and the Netherlands evaluated by the Center for Higher Education Development (CHE). Equally important, many of our ideas, particularly those related to the internationalization of universities, were adopted by other institutions and had a major impact on the reform of Higher Education in Germany, which took place at that time as part of the Bologna Process.

The University provided me with a brand-new laboratory and animal facility, which enabled me, together with the newly recruited lab members, to resume research activities relatively soon after my move from England to Germany. Over the next seven years, we made significant progress in several areas related to adult neurogenesis. In collaboration with Fred H. Gage of the Salk Institute for Biological Sciences in La Jolla, we established zebrafish as a novel, and now widely used model organism for studying adult neurogenesis (Zupanc et al. 2005). We demonstrated long-term survival of adult-born cells in this species (Hinsch and Zupanc 2007). By employing proteome analysis, we were the first to succeed in a large-scale identification of candidate proteins involved in brain repair in a regeneration-competent organism (Zupanc et al. 2006; Ilieş et al. 2012). We were also the first to isolate and cultivate adult stem cells from the teleost fish brain (Hinsch and Zupanc 2006). We developed a novel behavioral paradigm to study structural and, most importantly, also functional regeneration after spinal cord injury (Sîrbulescu et al. 2009). By employing this paradigm, we identified several of the key events that underlie successful spontaneous regeneration of spinal tissue, and we were able to link the structural repair to the recovery of behavioral function (Sîrbulescu et al. 2009; Sîrbulescu and Zupanc 2009; Sîrbulescu and Zupanc 2010a, b). At the neuroethological frontier, we discovered a new behavior (‘echo response’) of weakly electric fish (Zupanc et al. 2006; Gama Salgado and Zupanc 2011).

In spite of the enormous success in driving educational reform in Germany, the International University Bremen faced increasingly financial difficulties, like many other private universities in Germany. This crisis intensified during the time of the global financial turmoil in 2008. As a consequence, the University, now under new sponsorship and renamed ‘Jacobs University,’ shifted its research strategy from coverage of a broad range of disciplines to focus on a few select, and mostly applied areas. Despite the feeling of having been an active part of a major educational reform, I decided that it was time to move on.

 

From reduction to synthesis

In 2009, I joined Northeastern University in Boston, Massachusetts. In addition to my appointment as Full Professor, I served for the first three years of my tenure as Chair of the Department of Biology. In this capacity, I was responsible for over 1,300 students, staff, and faculty. Besides the usual administrative tasks, this position offered also a number of opportunities to leave some lasting mark for the benefit of the department: a nearly fifty percent growth in terms of student enrolment and tuition revenue, comprehensive reform of the graduate program, doubling of extramural funding, establishment of a new core instrumentation facility, and, perhaps most rewarding, hiring of several very talented faculty members.

During that time, I also started to share, through publications, some of my ideas on teaching and science policy issues with the scientific community and the public. These included, among others, reflections on how to teach zoology in the twenty-first century (Zupanc 2008), novel approaches to teaching of interdisciplinary subjects (Zupanc 2016, 2019b), global revolutions in higher education (Zupanc and Zupanc 2009), undergraduate research and inquiry-based learning (Zupanc 2012), use and misuse of the impact factor (Zupanc 2014), and the importance of collaboration, as opposed to cooperation, in science (Zupanc 2015).

Although my responsibility as chair limited my time for research, I was blessed in that two very capable post-docs from Bremen joined me for this new endeavor: Ruxandra F. Sîrbulescu, a cell biologist, and Iulian Ilieş, a statistician. Their efforts made it possible to establish the new lab relatively fast. To ease the transition process, Jacobs University supported us in keeping our research operation in Bremen active while the new lab was built and equipped in Boston.

Jointly, we decided to adopt a research strategy that promised to offer high returns but also came with higher risk: instead of focusing on smaller or mid-sized projects, we opted for a few large-scale projects. Although such projects required larger investments, the strategy paid off. Among other accomplishments, we succeeded in identifying A. leptorhynchus as the first vertebrate organism that does not exhibit any significant signs of brain senescence (Traniello et al. 2014). By employing a combination of behavioral, endocrinological, immunohistochemical, and proteomic analysis, as well as mathematical modeling, we detected a novel, glia-mediated mechanism that regulates the sexually dimorphic output pattern of a brainstem oscillator (Zupanc et al. 2014, 2019a). We carried out a de novo assembly, annotation, and proteomic validation of the central nervous system transcriptome of A. leptorhynchus (Salisbury et al. 2015). Furthermore, we developed a novel method for high-resolution mapping of tissue, and we used this approach to map the stem cells and their progeny in the pacemaker nucleus (Sîrbulescu et al 2014) and the spinal cord of A. leptorhynchus (Sîrbulescu et al. 2017).

In more recent years, I have become increasingly interested in integrating into a theoretical framework the wealth of data that we have collected over all these years through quantitative experimental work. Funded by a grant from the National Science Foundation, we are currently pursuing this new research direction through mathematical and computational modeling. Now, my training in physics three decades earlier proves invaluable, especially for translating biological processes into rules that can be used for modeling. In this effort, I have been joined by Rifat Sipahi, a colleague from the College of Engineering at Northeastern and an internationally recognized expert in agent-based computational modeling. Together, we have built new biologically inspired models of stem-cell-driven tissue growth (Ilieş et al. 2018; Sipahi and Zupanc 2018). Simulations based on these models have suggested previously unknown parameters, such as population pressure, play a critical role in regulating the growth of the tissue. Extending these models to tumors, we have been able to provide a theoretical explanation for the well-established phenomenon that anti-tumor drugs based on the induction of apoptosis may, in some types of tumor, result in promotion, instead of regression of tumor growth (Zupanc et al. 2019b).

To me, the most important outcome of these theoretical efforts is that they enable me to develop a much deeper understanding of certain biological phenomena, such as tissue growth or the function of neural oscillators, than was possible when I limited myself to reductionist approaches. At the same time, it is particularly satisfying that the detours I have taken from a straightforward career path, such as going back to college to study physics, or entering the field of developmental biology although my primary training was in behavioral neurobiology, now make perfect sense. I look forward to what might come next, including any detours!

 

References cited

Clint, S.C., Zupanc, G.K.H.: Neuronal regeneration in the cerebellum of adult teleost fish, Apteronotus leptorhynchus: guidance of migrating young cells by radial glia. Developmental Brain Research 130, 15-23 (2001)

Corrêa, S.A.L., Zupanc, G.K.H.: Connections between the central posterior/prepacemaker nucleus and hypothalamic areas in the weakly electric fish Aptero­notus lepto­rhynchus: evidence for an indirect, but not a direct, link. Journal of Comparative Neurology 442, 348-364 (2002)

Engler, G., Fogarty, C.M., Banks, J.R., Zupanc, G.K.H.: Spontaneous modulations of the electric organ discharge in the weakly electric fish, Apterono­tus lepto­rhynchus: a quantitative biophysical and behavioral analysis. Journal of Comparative Physiology A 186, 645-660 (2000)

Engler, G., Zupanc, G.K.H.: Differential production of chirping behavior evoked by electrical stimulation of the weakly electric fish, Apteronotus lepto­rhynchus. Journal of Comparative Physiology A 187, 747-756 (2001)

Gama Salgado, J.A., Zupanc, G.K.H.: Echo response to chirping in the weakly electric brown ghost knifefish (Apteronotus leptorhynchus): role of frequency and amplitude modulations. Canadian Journal of Zoology 89, 498-508 (2011)

Hinsch, K., Zupanc, G.K.H.: Isolation, cultivation, and differentiation of neural stem cells from adult fish brain. Journal of Neuroscience Methods 158, 75-88 (2006)

Hinsch, K., Zupanc, G.K.H.: Generation and long-term persistence of new neurons in the adult zebrafish brain: a quantitative analysis. Neuroscience 146, 679-696 (2007)

Ilieş, I., Sipahi, R., Zupanc, G.K.H.: Growth of adult spinal cord in knifefish: development and parametrization of a distributed model. Journal of Theoretical Biology 437, 101-114 (2018)

*Ilieş, I., *Zupanc, M.M., Zupanc, G.K.H.: Proteome analysis reveals protein candidates involved in early stages of brain regeneration in teleost fish. Neuroscience 219, 302-313(2012) [*these authors contributed equally to this paper]

Salisbury, J.P., Sîrbulescu, R.F., Moran, B., Auclair, J.R., Zupanc, G.K.H., Agar, J.N.: The central nervous system transcriptome of the weakly electric brown ghost knifefish (Apteronotus leptorhynchus): de novo assembly, annotation, and proteomics validation. BMC Genomics 16, 166 (2015)

Sipahi, R., Zupanc, G.K.H.: Stochastic cellular automata model of neurosphere growth: roles of proliferative potential, contact inhibition, cell death, and phagocytosis. Journal of Theoretical Biology 445, 151-165 (2018)

Sîrbulescu, R.F., Ilieş, I., Meyer, A., Zupanc, G.K.H.: Additive neurogenesis supported by multiple stem cell populations mediates adult spinal cord development: a spatiotemporal statistical mapping analysis in a teleost model of indeterminate growth. Developmental Neurobiology 77, 1269-1307 (2017)

Sîrbulescu, R.F., Ilieş, I. Zupanc, G.K.H.: Structural and functional regeneration after spinal cord injury in the weakly electric teleost fish, Apteronotus leptorhynchus. Journal of Comparative Physiology-A 195, 699-714 (2009)

Sîrbulescu, R., Ilieş, I., Zupanc, G.K.H.: Quantitative analysis reveals dominance of gliogenesis over neurogenesis in an adult brainstem oscillator. Developmental Neurobiology 74, 934-952 (2014)

Sîrbulescu, R.F., Zupanc, G.K.H.: Dynamics of caspase-3-mediated apoptosis during spinal cord regeneration in the teleost fish, Apteronotus leptorhynchus. Brain Research 1304, 14-25 (2009)

Sîrbulescu, R.F., Zupanc, G.K.H.: Effect of temperature on spinal cord regeneration in the weakly electric fish, Apteronotus leptorhynchus. Journal of Comparative Physiology-A 196, 359-368 (2010a)

Sîrbulescu, R.F., Zupanc, G.K.H.: Inhibition of caspase-3-mediated apoptosis improves spinal cord repair in a regeneration-competent vertebrate system. Neuroscience 171, 599-612 (2010b)

*Traniello, I.M., *Sîrbulescu, R.F., *Ilieş, I., Zupanc, G.K.H.: Age-related changes in stem cell dynamics, neurogenesis, apoptosis, and gliosis in the adult brain: a novel teleost fish model of negligible senescence. Developmental Neurobiology 74, 514-530 (2014) [*these authors contributed equally to this paper]

Zupanc, G.K.H.: Fische und ihr Verhalten. Die Erforschung der geheimnis­vollen Welt unter Wasser. Mit einem Geleitwort von Arthur Davis Hasler, Laboratory of Limnology der Universität Wisconsin in Madison (USA). 182 pp., ISBN 3-923 880-11-1. Tetra Verlag, Melle (1982)

Zupanc, G.K.H.: Fish and Their Behavior. How Fishes Live - Specially Written for Aquarists. Preface by Dr. Dr. h.c. Arthur Davis Hasler, Professor Emeritus at the University of Wisconsin in Madison (U.S.A.). 188 pp., ISBN 3-923 880-19-7. Tetra-Press, Melle (1985)

Zupanc, G.K.H.: Fish and Their Behavior. How Fishes Live - Specially Written for Aquarists. Preface by Arthur Davis Hasler, Professor Emeritus at the University of Wisconsin in Madison (U.S.A.). 187 pp. 2nd edition. ISBN 3-923 880-19-7. Tetra-Press, Melle (1988a)

Zupanc, G.K.H. (Editor): Praktische Verhaltensbiologie. Mit Beiträgen von Helmut Altner, Wilhelm Beier, Christiane Buchholtz, Martin Dambach, Benno Darnhofer-Demar, Klaus Dumpert, Dierk Franck, Reinhard Gerecke, Hartmut Greven, Volker Hahn, Ernst Kullmann, Jürg Lamprecht, Martin Lindauer, Hans Machemer, Ulrich Maschwitz, Marliese Müller, Rüdiger Schröpfer, Roland Sossinka und Günther K.H. Zupanc. Series: Pareys Studientexte 61. 274 pp. ISBN 3-489-62936-1. Verlag Paul Parey, Ber­lin/Hamburg (1988b)

Zupanc, G.K.H.: Fische im Biologieunterricht: Arten – Pflege – Beobach­tungen und Experimente. Series: Praxis-Schriftenreihe, Abteilung Biologie, Volume 37. Series-Editor: Wolfgang Jungbauer. 195 pp. ISBN 3-7614-1290-8. Aulis Verlag Deubner & Co KG, Köln (1990)

Zupanc, G.K.H.: The synaptic organization of the prepacemaker nucleus in weakly electric knifefish, Eigenmannia: a quantitative ultrastructural study. Journal of Neurocytology 20, 818-833 (1991)

Zupanc, G.K.H.: An in vitro technique for tracing neuronal connections in the teleost brain. Brain Research Protocols 3, 37-51 (1998)

Zupanc, G.K.H.: Behavioral Neurobiology: An Integrative Approach. Foreword by Theodore H. Bullock, University of California, San Diego. 342 pp. ISBN 0-19-870056-3. Oxford University Press, Oxford/New York (2004)

Zupanc, G.K.H.: Teaching zoology in the twenty-first century: old challenges and new opportunities. Journal of Zoology (London) 274, 105-106 (2008)

Zupanc, G.K.H.: Undergraduate research and inquiry-based learning: the revitalization of the Humboldtian ideals. Bioscience Education 19-10 (2012)

Zupanc, G.K.H.: Impact beyond the impact factor. Journal of Comparative Physiology-A 200, 113-116 (2014)

Zupanc, G.K.H.: Sharp eyes: How well can we really see? Science in School 37, 29-33 (2016); Supporting Material for follow-up physics experiments available online at http://www.scienceinschool.org/sites/default/files/teaserMaterial/vision_worksheet_0.pdf.

Zupanc, G.K.H.: Behavioral Neurobiology: An Integrative Approach. Foreword by Theodore H. Bullock. Third Edition. 384 pp. ISBN978-0-19-873872-5. Oxford University Press, Oxford/New York (2019a)

Zupanc, G.K.H.: Understanding the role of diffusion in synaptic transmission through inquiry-based learning & quantitative reasoning. American Biology Teacher 81, 435-441 (2019b)

Zupanc, G.K.H., Amaro, S.M., Lehotzky, D., Zupanc, F.B., Leung, N.Y.: Glia-mediated modulation of extracellular potassium concentration determines the sexually dimorphic output frequency of a model brainstem oscillator. Journal of Theoretical Biology 471, 117-124 (2019a)

Zupanc, G.K.H., Clint, S.C., Takimoto, N., Hughes, A.T.L., Wellbrock, U.M., Meissner, D.: Spatio-temporal distribution of microglia/macrophages during regeneration in the cerebellum of adult teleost fish, Apteronotus lepto­rhynchus: a quantitative analysis. Brain, Behavior and Evolution 62, 31-42 (2003)

Zupanc, G.K.H., Heiligenberg, W.F.: Sexual maturity-dependent changes in neuronal morphology in the prepacemaker nucleus of adult weakly electric knifefish, Eigen­mannia. Journal of Neuroscience 9 (11), 3816-3827 (1989)

Zupanc, G.K.H., Hinsch, K., Gage, F.H.: Proliferation, migration, neuronal differentiation, and long-term survival of new cells in the adult brain of zebrafish. Journal of Comparative Neurology 488, 290-319 (2005)

Zupanc, G.K.H., Horschke, I.: Proliferation zones in the brain of adult gym­noti­form fish: a quantitative mapping study. Journal of Comparative Neurology 353, 213-233 (1995)

Zupanc, G.K.H., Ilieş, I., Sîrbulescu, R.F., Zupanc, M.M.: Large-scale identification of proteins involved in the development of a sexually dimorphic behavior. Journal of Neurophysiology 111, 1646-1654 (2014)

Zupanc, G.K.H., Kompass, K.S., Horschke, I., Ott, R., Schwarz, H.: Apoptosis after injuries in the cerebellum of adult teleost fish. Experimental Neurology 152, 221-230 (1998)

Zupanc, G.K.H., Maler, L.: Evoked chirping in the weakly electric fish Aptero­notus leptorhynchus: a quantitative biophysical analysis. Canadian Journal of Zoology 71, 2301-2310 (1993)

Zupanc, G.K.H., Ott, R.: Cell proliferation after lesions in the cerebellum of adult teleost fish: time course of generation, site of origin, and type of new cells produced. Experimental Neurology 160, 78-87 (1999)

Zupanc, G.K.H., Zupanc, F.B., Sipahi, R.: Stochastic cellular automata model of tumorous neurosphere growth: roles of developmental maturity and cell death. Journal of Theoretical Biology 467, 100-110 (2019b)

Zupanc, G.K.H., Zupanc, M.M.: Birth and migration of neurons in the central poste­rior/pre­pacemaker nucleus during adulthood in weakly electric knifefish, Eigen­mannia sp. Proceedings of the National Academy of Sciences U.S.A. 89, 9539-9543 (1992)

Zupanc, G.K.H., Zupanc, M.M.: Global revolutions in higher education: the international schools’ perspective. The International Schools Journal 29 (1), 50-59 (2009)

Zupanc, G.K.H., Sîrbulescu, R.F., Nichols, A., Ilies, I.: Electric interactions through chirping behavior in the weakly electric fish, Apteronotus leptorhynchus. Journal of Comparative Physiology A 192, 159-173 (2006)

Zupanc, M.M., Wellbrock, U.M., Zupanc, G.K.H.: Proteome analysis identifies novel protein candidates involved in regeneration of the cerebellum of teleost fish. Proteomics 6, 677-696 (2006)