A conversation with Dr. Jiami Guo, PhD on receiving two significant awards

Dr. Jiami Guo, PhD, is Child Health & Wellness Researcher, Precision Medicine & Disease Mechanisms Program; Assistant Professor in the Department of Cell Biology & Anatomy at UCalgary’s Cumming School of Medicine (CSM); and a member of the Hotchkiss Brain Institute and the Alberta Children’s Hospital Research Institute at the CSM.

Dr. Guo was recently awarded a Spring 2020 CIHR Project Grant, as well as a New York Stem Cells Foundation (NYSCF) Robertson Neuroscience Investigator Award for her research – two important awards that will greatly impact her ability to advance her research. We sat down with Dr. Guo to learn more.

Q: Tell me about your research for which you are being awarded these important grants.

Jiami Guo: The main goal of our research is to identify fundamental principles governing the construction of neural circuits in development and disease. Towards this goal, we are focused on the dynamic function of the primary cilium, a tiny signaling antenna of a cell. Primary cilia are present virtually on all cell types and are essential for coordinating major cell functions in response to environmental signals. The critical role of primary cilia in brain development is evident in human disease states called ciliopathies, where defective cilia lead to brain malformations associated with neurodevelopmental disorders such as autism and intellectual disabilities. We use a combination of mouse ­­genetics, innovative cilia-specific signaling modulation, and viral-genetic circ­uit mapping to delineate primary cilia in the emergence of neuronal morphology and connectivity, key steps in neural circuits formation.

By assembling a holistic view of how primary cilia translate environmental signals to impact neural development, we aim to not only uncover undefined cell biological mechanisms fundamental for neural circuit construction and malformation, but also to advance our understanding of how genetics and environment interact to contribute to the causes of neurodevelopmental disorders.­

Another goal of our work is to understand how the cerebellum functionally wires up with the cerebral cortex and how this circuitry emerges during development. This information is necessary to understand the function of cerebellum in higher order brain functions and the contribution of cerebellar malformations to mental disorders.

Q: Are both awards for the same area of research?

JG: Yes, they are both about dissecting the role of primary cilia in the brain, but each with different focus.

Q: How will these awards impact you, your team and your research?

JG: This support is very important for my team at this early stage. The combination of these two awards at this early stage means that we can focus on improved research ideas without worrying too much about financial restrictions, which is a huge relief for my team and me. The CIHR project grant will support our immediate research goals and help start my ‘bread and butter’ research projects. The NYSCF award, thanks to its unlimited funding nature, offers tremendous freedom and flexibility in terms of kicking off riskier but potentially more rewarding projects for our long-term goals.

Q: What question(s) or challenge(s) were you setting out to address when you started this research?

JG: The CIHR project grant will support one project studying the role of primary cilia in axonal development. The NYSCF Robertson Neuroscience award is a career award that will support my whole research program focused on assembling a holistic view of how primary cilia convey environmental signals to impact neural development by peeling back the layers of this mystery from gene→cell→circuit→behavior→therapeutics. Due to recent advances in human genetics, we already know that primary cilia have a significant impact on brain development: mutations in 100+ ciliary genes can lead to 30+ human disorders, many of which show severe brain malformations and functional deficits. However, due to the small size of cilia and sophisticated structure, the study of cilia has long been challenged by the lack of tools to study the cilia-specific signaling events.

To solve this problem, for both awards, we aim to create and use the most state-of-the-art technologies in live cell imaging and cell signaling control to dissect primary cilia function with unprecedented power and precision. We aim to not only uncover an undefined cilia-centered, cellular pathway fundamental for brain construction and formation, but also to advance our understanding of how genetic and environmental insults interact to contribute to the causes of neurological disorders.

Q: Are there key findings/discoveries you can tell us about with regard to this research?

JG: We recently found that primary cilia, only a few um long on the neuronal cell soma, can trigger signals that rapidly travel in the whole cell body and elicit neuronal morphological and signaling changes. This phenomenon was never observed before and not quite expected either. This finding points to the exciting picture that primary cilium can function as a remote control to help instruct how neurons respond to their dynamic environment in the brain. A better understanding of this process will potentially bring important insights into how the cells in our brain can constantly adapt to the ever-changing brain chemistry and functional states in health and disease.

Q: Why is this research important, and to whom is it important (people living with autism/intellectual disabilities; other neuroscientists)?

JG: Emerging evidence suggests overlaps in the genetics and etiology of neurodevelopmental disorders such as schizophrenia, autism spectrum disorder (ASD) and intellectual disabilities (ID). The identification of common biological vulnerabilities that underlie the shared pathophysiology is critical for the development of effective therapeutic interventions. We propose that primary cilia, unique in its ability to function as an integrative sensor and conveyor of critical environmental signals during circuit formation, represents one of such biological vulnerability. Thus, primary cilia are associated with common risk factors for a broad range of neurodevelopmental disorders such as ASD and ID. It is possible that ciliary dysfunction is also linked to dementia, Alzheimer’s disease, and brain cancer.

Q: How might this research impact people in the future?

JG: One of our drug screen efforts will tell us how primary cilia may detect a wide range of signals in the brain to mediate both positive and negative effects. For example, cilia can be extremely sensitive to certain environmental factors such as pollutants, food additives, and psychiatric drugs. The knowledge of what factors are stimulating cilia in our brain and what are the consequences of the ciliary activity in brain development and function could open up new lines of pathological mechanistic investigation and novel therapeutic avenues.  

Q: You are the lead principle investigator in these studies. Who are the other collaborators, and their roles?

JG: We will start collaborating with a diverse group of scientists within and outside of UCalgary who offer complementary expertise. 

Q: Who is funding this research?

JG: Thank you to ACHRI, CSM, CIHR, NSERC, NYSCF

Q: Where can we find more information?

JG: https://www.sciencedirect.com/science/article/pii/S1534580719309360. Developmental Cell, 2019.

Q: Your research sounds fascinating, and is sure to lead to discoveries that result in better outcomes for those living with neurodevelopmental disorders. Congratulations on your success with these two significant awards and thank you for sharing your story with us.