Appearing at regular intervals in YFile, Open Your Mind is a series of articles offering insight into the different ways York University professors champion fresh ways of thinking in their research and teaching practices. Their approaches, grounded in a desire to seek the unexpected, are charting new courses for future generations.
Today, the spotlight is on Georg Zoidl, a professor in the Faculties of Health and Science.
Zoidl, who is a Canada Research Chair Tier 1 in molecular and cellular neuroscience, has focused his research interests on identifying how cells of the eye and brain communicate through specialized cell junction, and to determine how changes in cell junctions lead to vision, learning and memory impairment.
Q. Please describe your field of current research.
A. The long-term vision of my research program aims to clarify how cells of the eye and the brain communicate through specialized cell junctions, called gap-junctions or electrical synapses, and how changes in this process can lead to impairment of vision, learning and memory.
My group exploits two complementary strategies to investigate the roles of gap-junctions in health and disease:
- The molecular, cellular and structural basis of gap-junction functions is studied using cell-based models in vitro. Outcomes of this approach provide important insight into the molecular machinery enabling this mode of communication between cells of the nervous system and how this machinery is altered – for example, by seizures at the cellular level.
- The second direction of research capitalizes on recent advances in genome engineering of whole organisms. We edit the genome of the zebrafish and introduce tailored mutations affecting gap-junction communication between nerve cells. In this process, we continue to develop models of human disease, which allow us to investigate fundamental biological, as well as pathological, processes related to vision, learning and memory from genes to organisms.
Q. What inspired you to pursue this line of research? Who or what sparked your interest in this line of inquiry?
A. Epilepsy is a central nervous system (CNS) disorder in which communication between nerve cells is altered, causing seizures with periods of unusual behaviour, sensations and memory loss. Worldwide epilepsy affects more than 50 million people of all age classes at huge socio-economical costs (estimated $19.2 billion in 2010). Pharmacological treatment and surgical options are limited, and approximately one-third of patients are resistant to available anticonvulsant drugs, in part because of our lack of understanding of the underlying pathophysiology.
My most recent research is motivated by the fact that memory loss and visual disturbances are common dysfunctions observed in patients with seizures, indicating a temporary loss of communication between nerve cells. I first became interested in the role(s) of gap-junctions in seizures and epilepsy when major findings, including our own, demonstrated that the expression of some gap junction proteins overlapped with regions affected by epileptic seizures. Today, scientific evidence strongly suggests that gap-junction communication between nerve cells is intimately related to epilepsy and seizure generation, but the mechanistic details and how this communication can be manipulated for therapeutic purposes remains to be shown.
Q. How would you describe the significance of your research in layperson’s terms?
A. My program of research is interdisciplinary, scalable, translational and will close a significant knowledge gap. Together with clinical and industrial partners, we are starting preclinical drug screening. Potential outcomes will apply to other disorders with seizures, such as fetal alcohol spectrum disorder, and Alzheimer’s and Parkinson’s diseases.
Q. How are you approaching this field in a different, unexpected or unusual way?
A. In Canada, my group is the first to use advanced genome engineering methods to develop models of human disease by editing gap-junction communication in the nervous system of the zebrafish. Together with collaborators at St. Michael’s Hospital and the Mayo Clinic, we are in the process of optimizing a procedural pipeline that will allow us to develop models and use them for high-content and high-throughput functional imaging and drug screening.
Q. How does your approach to the subject benefit the field?
A. This research will close a significant knowledge gap and has the potential to lead to new targets for drug development. Further, we continue to create and characterize unique disease models that will be made available through collaboration, purchase or by instructing others to develop their own.
Q. What findings have surprised and excited you?
A. The most recent exiting discovery was when we started analyzing the first zebrafish models generated at York University and a behavioural abnormality was discovered in line with our working hypothesis of how gap-junction communication operates. This discovery actively encourages my graduate students and me to pursue new lines of inquiry at an organismal level.
Q. Every researcher encounters roadblocks and challenges during the process of inquiry. Can you highlight some of those challenges and how you overcame them?
A. Roadblocks can come from any direction, but most of the time it is about securing funding and access to or maintaining infrastructure. Luckily, my home Faculties and the VPRI (Vice-President Research & Innovation) office are very supportive and efficient at finding solutions. At a more personal level, it is important for me to to believe in my team, listen to critics and do a constant reassessment of my goals and my performance.
Q. How has this research opened your mind to new possibilities or new directions?
A. I am constantly looking out for new developments and technologies that might enable me to reach the goals of my research program faster and more efficiently. Developing zebrafish models of human disease using precise genome engineering tools was virtually impossible a few years ago, but we managed to introduce this frontier of science at York University. This enables us to tackle another frontier in biomedical research, combining disease model development with high-throughput behavioural and drug screening.
Q. Are there interdisciplinary aspects to your research? If so, what are they?
A. My lab has expertise in molecular and cell biology, biochemistry, genomics and proteomics, anatomy and histology, and live cell imaging. We use genome engineering to develop our own animal models and currently expand our portfolio of behavioural phenotying methods to study vision, learning and memory. Further, students in my laboratory benefit from collaborations with local expertise in structural biology or bioengineering, and our clinical partners at St. Michael’s Hospital and the Krembil Neuroscience Centre.
Q. Did you ever consider other fields of research?
A. While I am interested in other research fields, I don’t consider switching. However, I am following very closely technological developments in other areas outside my field, with a particular focus on optogenetics/photonics, pharmacological genomics and proteomics. Bioengineering is another field of interest, and I have started collaborations to exploit high-content and high-throughput technologies.
Q. How long have you been a researcher?
A. I started my first postdoc in 1990 at the Clinic of Neurology, which is part of the Medical School of the Heinrich-Heine-University in Duesseldorf, Germany. Joining the research group led by my mentor and colleague Dr. Hans-Werner Muller, I was entrusted with a research project that allowed me to be the first describing a function of the gene that causes Charcot-Marie-Tooth Type 1A neuropathy, the most common inherited neurological disorder in humans.
Q. Are you teaching any courses this year? If so, what are they? Do you bring your research experience into your teaching practice?
A. I just finished teaching SC/BIO4370 – Neurobiology in fall. In this fourth-year course, I have a steady attendance of 50 to 60 amazing and bright students each year. Class discussions, and those face-to-face before and after the class, demonstrate that neurobiology is a point of significant interest in our undergraduate student community. Without doubt, I can say that many of my students are drawn to the subject because they wish to understand how the brain works and how to develop new strategies to cure disorders of the nervous system. To satisfy this interest, I use my long-term teaching background at medical school to exemplify the functions of the nervous system through human neurological disorders.
Q. What advice would you give to students embarking on a research project for the first time?
A. The Zoidl lab has four commandments: communicate, because talking with your peers or me is the fastest road to avoid errors; be prepared, because when you don’t line up all you need for your experiments in time there is a very high likelihood to fail; check, check and check again, because you are prone to make mistakes, which can be costly and make your supervisor unhappy; be realistic and accept that you start from zero. A teaching lab doesn’t prepare you for a real research project, but as a team we will help you to learn fast.
Tell us a bit about yourself:
Q. What books, recordings or films have influenced your life?
A. Growing up in the ’70s and ’80s in Germany, at a time when men flew to the moon, made great scientific discoveries, but also experienced deep social, political and economical conflicts, my formative years were influenced by authors like R.C. Heinlein, I. Asimov or A.C. Clarke. Within the framework of science fiction stories, these authors raised my curiosity towards social and technological themes: the importance of individual liberty and self-reliance, the obligation individuals owe to their societies, the influence of organized religion and technology on culture and government, or how any of this affects human cultural practices. I think these topics are timeless and as relevant now as then.
Q. What are you reading and/or watching right now?
A. My wife gave me as a present Gratitude by the late neurologist Dr. Oliver Sacks. I am a long-time follower and reader of his books. His recent death was a very sad moment. Gratitude is a short, wonderful, bittersweet meditation on facing death with grace, while cherishing life. Thank you, Dr. Sacks!
Q. If you could have dinner with any one person, dead or alive, who would you select and why?
A. I choose my wife. She is the backbone of my family life, and we both enjoy gourmet dining. In case there is space for others, I would choose family and friends back in Germany.
Q. What do you do for fun?
A. Tennis, volleyball, biking or a good workout at the gym.