BY EKİNSU POLAT (AMER/II)
ekinsu.polat@ug.bilkent.edu.tr
Prof. Özçelik graduated from İstanbul University, İstanbul Medical School in 1986. He completed his postdoctoral work in physiology at the Ludwig-Maximilians-Universität München and in human genetics at the Yale University School of Medicine and the Howard Hughes Medical Institute, Stanford University School of Medicine. He returned to Turkey in 1992 as assistant professor and founding head of the Department of Genetics at DETAM, Istanbul University. He introduced DNA-based individual identification to the Turkish judiciary system and also led diagnostic genetics laboratories at Istanbul and Bilkent Universities. Currently, he works on the complex phenotypes of obesity and metabolic disorders in collaboration with Rockefeller University. Dr. Özçelik is a member of the Turkish Academy of Sciences, serving as a counselor, board member and education committee chair of the European Society of Human Genetics, program committee member of the American Society of Human Genetics and past president of the Turkish Society of Medical Genetics. He received the TÜBİTAK Young Investigator Award in 1996, Bayındır Medical Award in 2006 and TÜBİTAK Science Award in 2012. The American Society of Human Genetics, the leading and largest genetics organization in the world, designated Dr. Özçelik as “2023 thought leader.” In 1995, he joined the Department of Molecular Biology and Genetics at Bilkent University. He was named associate professor in 1994 and professor in 2004. He was appointed as the Dean of the Faculty of Science in 2012. He teaches MBG 110 (Introduction to Modern Biology) and MBG 488/601 (Human Genetics) during the fall semester.
What has been the most exciting moment of your career so far?
I have had more than one exciting moment in my career. Let me give you two examples of the discoveries that we’ve made. Identification of the Prader-Willi syndrome locus, which was selected as the most significant discovery of 1992 in genetics by one of the major journals in the field,”Nature Genetics.” There is also the discovery of the causal relationship between the circadian clock and human behavior, which was selected as the most significant discovery of 2017 by Cell.
What’s one piece of information from your field that you think everyone should know?
My field is human genetics, and we touch the lives of people afflicted with genetic disorders. As geneticists, we are not reactionary, meaning we do not function when diseases strike. Instead we take an actionary approach and use genetic information to prevent diseases from happening.
When and where do you do your best thinking?
Usually when I take a shower in the morning. My afternoon hours are also productive in terms of writing papers. Then the midnight strikes: I sometimes wake up in the middle of the night and start thinking so clearly that I figure out something that is perplexing to me. It is kind of a revelation.
What distracts you?
Negative thinking and people whose default setting is “No.”
What are you most curious about?
Nature, how genes work and the mechanisms of inheritance.
What’s the most common misconception about your work?
That it is difficult and boring. On the contrary, what we do is fun.
What do you like to do when you’re not working?
Nowadays, watching YouTube. There are so many excellent opinion pieces, historical analyses, cultural developments. I also enjoy watching Netflix.
Which books have influenced you the most, and why?
Of course, there are several novels that have influenced me. But I would like to answer your question by citing an autobiography that I read when I was a medical student, that of Dwight Eisenhower, the 34th US president. His letter to get into WestPoint Military Academy inspired me to shape my future career in terms of getting accepted to Yale and Stanford Universities.
If you weren’t an academic, what career would you choose?
I do not think I can do anything other than academics. Having said this, I do also like architecture.
What’s the secret to leading a happy life?
Having patience, making wise decisions, living in a peaceful and loving home environment, and harmony at work.
If you could go back to your undergraduate/graduate student years, what advice would you give to your younger self?
Once one of my professors said, “Follow the road that you yourself perceive as the straight and do not divert.” I am lucky that I heard this advice at a young age.
Why did you choose an academic career?
Because I like asking questions and searching for answers. A research-based career is the ideal path to take for such people.
Why/how did you choose Bilkent?
In 1993, Salim Çıracı, the Dean of the Faculty of Science, invited me to Bilkent. I came to Ankara and saw the beautiful campus, the academic environment and the visionary leadership, which convinced me that Bilkent was the place for my academic career.
What do you like the most about being at Bilkent?
Being surrounded by young and bright minds, a beautiful campus environment and an institutional quest for excellence.
What projects are you working on currently?
Currently, we are working on the deciphering of the invaluable genetic information in the Turkish Variome. This is a resource that my group established during the past 12 years with over 10 million dollars of grant funds. Close to 4000 individuals have been analyzed by DNA sequencing and with compilation of their health records. We are conducting an international project with the participation of Bilkent, Cambridge, Harvard, McGill and Rockefeller Universities as well as with Mount Sinai Medical School and University of Texas, Southwestern Medical School to decipher the molecular determinants of brown fat tissue and extreme forms of obesity. In conjunction with these studies, we ask fundamental questions as to inheritance models in human diseases. I am also a steering committee member of an international working group on genetic predisposition to infectious diseases. We recently discovered the genes responsible for inherited predisposition to COVID-19 and tuberculosis. We develop novel AI tools for analysis of human genetic data. These are the projects that keep me going.
What’s your best work?
There are two. First, the discovery of the Prader-Willi syndrome gene SNRPN. This was not a straightforward gene discovery exercise. In 1992, we had little knowledge of genes and we were hardly aware of the existence of what is called pseudogenes. Unfortunately, pseudogenes make it very difficult to identify a real gene. We overcame this hurdle and it was hailed as a groundbreaking discovery by the scientific community. Second, human behavior is notoriously difficult to decipher in terms of genes that are involved in sleep patterns, anxiety, depression, attention deficit hyperactivity disorder, bipolar disorder or schizophrenia (to name a group of major ones). One day it occurred to me that we always define a disease and then search for the gene that causes the disorder. I said, “Why don’t we reverse the process and first pick a gene and see what kind of diseases arise in people who carry a faulty version of the chosen gene.” This is how we identified that the core body clock gene Cryptochrome 1 causes delayed sleep phase disorder in humans. This project was conducted in collaboration with 2017 Nobel Laureate Michael Young. We went on to discover that people with Cryptochrome 1 mutations suffer from attention deficit hyperactivity disorder and disturbed sleep, which is a common occurrence in psychiatric disorders. Last year, Chinese scientists developed transgenic mice with Cryptochrome 1 mutations. Guess what happened? Mice also display attention deficit and hyperactivity disorder characteristics.
What excites you about your work? What’s the coolest thing about your work?
That we are entirely bound by our own imagination.
Could you share a turning point or defining moment in your career?
Sure, here is one: As a visiting medical student at Yale, I was in the outpatient clinic with my supervisor one day. An important looking physician walked in and asked my supervisor what was wrong with the patient. She said, “epilepsy.” He asked, “What type of epilepsy?” and she replied, “We think temporal lobe epilepsy.” Then he turned to me and said, “What do you think?” and I said, “It may very well be temporal lobe epilepsy but we need further investigation.” He said, “Why?” and I said, “The patient is describing episodes of pleasant smell, however temporal lobe epilepsy is frequently associated with unpleasant smell. That is why we need to go deeper.” He turned to my supervisor and asked, “Who is he?” I think this was the defining moment; the elderly physician was the Dean of the Yale Medical School and next I found myself as a young doctor working at Yale. Here is another one, if space permits: After we discovered the quadrupedal locomotion gene in 2010, it was news all over the world. The phenotype is super interesting, and the scientific methodology we employed was favorably reviewed by the scientific community. One day I got the news that a very prominent geneticist at Rockefeller University wanted to talk to me regarding our discovery and the prospect of a future collaboration. One would next expect an exchange of email messages. But I said to my wife, “Iclal, this is such a great opportunity that it deserves a face-to-face meeting.” Soon enough, we were on a plane to the US. This was truly a turning point in my career and how we secured funds for the Turkish Variome project. Lastly, I was selected as the “2023 thought leader” by the American Society of Human Genetics, the largest biomedical genetics organization in the world. This is now my 39th year in human genetics and 43rd year in science. As you may guess it was a tremendous honor for me.
