Summer Students Q&A
At ENRRICH we love to highlight all the work our student researchers are doing. This summer we were lucky to have the recipients of our first ENRRICH studentship working on unique projects. We asked all four what they were working on and what they learned during the summer term. This year our students’ projects demonstrated the broad range of topics being researched by ENRRICH members. We’ll be featuring two students each month in September and October. The first two are featured below.
Name: Adedayo Oladejo
Supervisor: Dr. Paul Marcogliese
What was your project about?
The title of my project was characterizing the neuronal role of CK2 using Drosophila melanogaster.
My project involves understanding the role of a protein complex, called CK2 in neurological disorders. CK2 is made up of two proteins encoded by the genes, CSNK2A1 and CSNK2B. Specific changes in either CSNK2A1 or CSNK2B lead to neurodevelopmental syndromes in children. These neurodevelopmental syndromes are characterized by epilepsy, developmental delay, and intellectual disability. CK2 is mostly found in the nerve cells of the brain (neurons). The aim of this study is to see what happens when we knockdown (remove) the gene (CSNK2A1 or CSNK2B) in a fruit fly model. This will help develop a model without the gene that can be used to test potential treatments and understand the molecular pathways involved in disease.
What made you decide to work on this topic?
Having learnt how fascinating a model Drosophila melanogaster (commonly known as fruit flies) is and how it can be used as a tool to study human diseases during my Honours thesis Project in Dr Marcogliese’s Laboratory, it was an easy decision for me to continue working on this project. Fruit flies are ideal model organisms because they have a rapid reproduction time, and they share about 60% of genes with humans. Importantly, about 85% of genes that are involved in human disease are found in the fly genome. They’re also relatively inexpensive to maintain.
What approach did you take and what were your results?
I tried to assess the role of CK2 in neurons and other types of brain cells called glia during fruit fly development and in the adult stage by removing CK2 using a specific biochemical method for studying gene expression and functions. I conducted a neuronal knockdown, an adult specific neuronal knockdown and finally a glial knockdown at varying temperatures. This allowed me to control how much CK2 was knocked down in each cell type.
When CK2 was knocked out, or completely removed from neurons during development, the fruit flies did not survive. In flies where CK2 was not completely removed, we saw wing defects that resulted in not being able to fly. Thus, we concluded that neuronal CK2 is critical for the development of fruit flies.
Removing CK2 from adult fruit flies led to decreased life span and negatively effected the fruit flies’ ability to climb. We concluded that this CK2 protein is important for long term neuronal function. Finally, removal of CK2 in glia had no significant effect.
What do you feel are the greater implications of your research?
I feel this project will shed light on the nature of variants implicated in Poirier-Bienvenu neurodevelopmental syndrome (POBINDS) as related to CSNK2B and Okur-Chung neurodevelopmental syndrome (OCNDS) as related to CSNK2A1. These two disorders are related to the CK2 protein complex. Future studies will develop genetic variants related to these conditions and express them in fruit flies. This will help us understand basic biology, the nature of the variants, as well as pathogenesis of diseases.
What lessons did you learn?
I have learned how to make and give scientific presentations. I have also learned that science takes time. Having been working on this project for the last 10 months, I have had to repeat this experiment multiple times just to make sure my results are consistent and can be reproduced.
Name: Mason Hollebeke
Supervisor: Dr. Galen Wright
What was your project about?
Autism Spectrum Disorder (ASD) is a highly heritable neurodevelopmental disorder that affects how people interact, communicate, learn, and behave. Although ASD can be diagnosed at any age, it is characterized as a “neurodevelopmental disorder” as symptoms generally appear in the first two years of life. The worldwide prevalence of ASD is around 1%. Much ASD research focuses on identifying genes robustly associated with ASD risk [1]. My current research is attempting to learn more about these genes using advanced computational approaches.
What made you decide to work on this topic?
Volunteering at the Children’s Hospital and working with children through Learn to Skate has inspired me to study a neurodevelopmental disorder. Witnessing the unique challenges and remarkable resilience of children affected by autism spectrum disorder (ASD) has evoked curiosity to understand this condition. This firsthand experience has fueled my desire to contribute to advancing knowledge in the field.
What approach did you take and what were your results?
The beginning of the project consisted of me learning as much as possible about ASD and the genetics that contribute to the disorder. We then went to a database that has been created by the Simons Foundation Autism Research Initiative (SFARI), which curates research on the genetics of ASD. SFARI lists over 1,200 genes that have been implicated in ASD, with annotations and links to published papers. This evolving database is an excellent resource for researchers as it helps track the expanding knowledge on ASD genetics. We then performed a bioinformatic analysis using a machine learning algorithm to determine what genomic properties can help distinguish SFARI genes from other genes in the human genome. We found that genes associated with ASD are more conserved across species and tend to be more complex than other genes in the genome.
What do you feel are the greater implications of your research?
By studying the genetics contributing to ASD, researchers aim to unravel its biological and genetic underpinnings and strive to enhance our understanding of cognitive diversity and neurodevelopmental variations. This knowledge fosters a more inclusive and empathetic society, promoting acceptance and support for individuals with autism.
Lessons learned:
I learned so much from this project. One thing I took away from the project was that the process of completing research sometimes does not go according to plan. This was a good reminder that a few bumps in the road are normal. It is important to remember that research exists to explore the unknown and uncertainty, making the research process unpredictable.
References:
1. Lord, C., Brugha, T., Charman, T., Cusack, J., Dumas, G., Frazier, T., Jones, E. J., Jones, R. M., Pickles, A., State, M. W., Taylor, J. L., & Veenstra-VanderWeele, J. (2020). Autism spectrum disorder. Nature Reviews Disease Primers, 6(1). https://doi.org/10.1038/s41572-019-0138-4