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 next two are featured below.
Name: Deborah Owoyemi
Supervisor: Dr. Robert Beattie
What was your project about?
The title of my research project is "Analyzing the Role of FAN1 in Regulating Neurodevelopment." Neurodevelopment is a fascinating process that explains how the brain grows during the early stages of life. Think of it like a complex mosaic being put together piece by piece. As an individual develops in the womb and during the early years of life, their brain cells, known as neurons, start to connect and create a vast network of communication.
Neurodevelopment starts with the formation of the neural tube, which is the foundation of the brain. From there, the neural tube develops into various parts, including the cerebral cortex. The cerebral cortex is the outermost layer of the brain and is responsible for advanced thinking, learning, and cognitive abilities amongst many other functions. Certain genes can affect the way our brain mosaic is put together.
My gene of interest is the FAN1 gene, short for FANCD2/FANCI-Associated Nuclease 1. This gene is crucial for maintaining and repairing DNA. The FAN1 gene produces an enzyme called a nuclease and is found in the central nervous system. Its job is to cut DNA strands at specific places. FAN1 specializes in repairing and processing abnormal DNA structures, including those with repeating sequences. This helps to safeguard genetic information and maintain the stability and integrity of the genome.
My summer research objective was to identify which cells in the cerebral cortex require FAN1, since it is heavily impacted during neurodevelopment.
What made you decide to work on your topic?
The topic of analyzing the role of FAN1 in neurodevelopment is fascinating to me because it delves into the inner workings of how our brains grow and function. Learning about FAN1, which is like a helper molecule in this process, sparks my curiosity. Various disorders and conditions have been linked to changes in FAN1, including neurodevelopmental issues and certain types of cancer. Multiple FAN1 variants have been associated with diseases such as autism, schizophrenia, epilepsy, and Rett syndrome. In mouse models of Huntington's disease, the absence or altered activity of FAN1 has been linked with developing symptoms related to Huntington’s disease at an earlier age. Another study has shown that FAN1 variants can improve the health and lifespan of mice with Rett syndrome. This led me to question, how does the presence or absence of FAN1 influence neurodevelopment?
Exploring the role of FAN1 is like delving into the mysteries behind the development of our brain from a tiny bundle of cells to a complex thinking machine.
What approach did you take and what were your results?
I conducted my research using a mouse model study, as mice and humans share around 85-90% of their genetics. Many genes that control brain development and function in humans also exist in mice. Both mice and humans' cerebral cortex have six cortical layers, making them structurally similar. The basic structure of the cerebral cortex is established at birth, and then refinement and maturation continue throughout infancy and childhood.
To achieve the goal of understanding which cells in the cerebral cortex require FAN1, my lab team and I bred two mice with one expressed and one unexpressed allele (+/-) of the FAN1 gene. This breeding was significant because their offspring had varying genotypes, some having both alleles expressed (+/+), some being heterozygous like their parents, and some having no expressed FAN1 gene on either allele (-/-). We analyzed and examined the cortex of these pups with different genotypes to determine the FAN1 populations when it is fully, partially, and not expressed. This could provide insights into the connection between the FAN1 gene and brain health and functioning.
What do you feel are the greater implications of your research?
By understanding how the FAN1 gene works in different situations, we can gain valuable insights into its effects on brain development and function. This knowledge may pave the way for new treatments or management strategies for conditions associated with this gene, such as Rett syndrome. Analyzing the impact of FAN1 on brain cells and tissues can also enhance our knowledge of its involvement in the creation of connections between neurons and contribute to a better understanding of neurological disorders.
What lessons did you learn?
Working as a summer student at ENRRICH was truly a transformative experience for me. I had the chance to improve my research skills and develop as a scientist, which was not an easy task. However, the effort I put in was worth it, as it allowed me to dig deeper into my research and improve my critical thinking skills. Throughout my research journey, I was able to sharpen my laboratory techniques, collaborate with other researchers, enhance my presentation skills, build a valuable network of contacts, and form lifelong bonds and friendships. This experience not only expanded my knowledge of neuroscience but also broadened my perspective of the field, enabling me to set up a solid scientific foundation that I can build on for years to come.
Name: Bresham Omar
Supervisor: Dr. Geoffrey Hicks
What was your project about?
Translating to the Community (T2C) is a collaborative study focused on creating a diagnostic biomarker “signature” for risk of Fetal Alcohol Spectrum Disorder (FASD) outcomes. Applying it towards early detection of FASD can have a major effect on the lives and development of children and families. Our lab also works on reducing or preventing FASD through vitamin A supplementation. I was involved in these projects through patient sample processing, genotyping, training for sample collection and qualitative interviewing, as well as through additional lab work involving molecular biology and imaging mouse model embryos.
What made you decide to work on your topic?
What attracted me to the research is the unique approach of the project. Also, the chance to experience both research in the lab and see how the lab work directly impacts children and families in the clinic and community were important to me. My initial experiences in the clinic helped me understand the difficulties faced in diagnosing FASD, and how much receiving a diagnosis helps children and families. These experiences made me become more specifically invested in the project and develop an interest in obtaining a clearer picture of FASD.
What approach did you take and what were your results?
Our lab works on two different models of FASD – mouse models and human cohorts. Our mouse model is looking at the connection between vitamin A (retinol, which gets broken down to retinoic acid), alcohol metabolism, and the direct role of retinoic acid in the early neurodevelopmental issues that result in FASD. By understanding how this works in a developing organism at a molecular level, we will be able to see if the mitigation or prevention of FASD outcomes through vitamin A supplementation is possible. The Translating to the Community (T2C) project uses human cohorts to validate our proposed signature by genetic analysis of their DNA samples. This study will help us get a clearer picture of the risk of FASD outcomes which, in turn, could help children with FASD get earlier access to care and early interventions known to significantly reduce the development of secondary disabilities.
What do you feel are the greater implications of your research?
If our work with vitamin A is successful, it could result in the ability to prevent or mitigate effects of FASD by simply taking vitamin A supplements during reproductive years – similar to taking folic acid to prevent spina bifida. Our work in early intervention, meanwhile, may have a significant impact through the potential to identify FASD earlier in affected children, to provide them with additional supports as they learn and grow, and to help mitigate any struggles they may face. The broader result of this could be kids facing fewer difficulties at school and in their day-to-day life due to receiving the support that is best for them, rather than just that which is “standard” for all.
What lessons did you learn?
I learned that research involves a lot more than just lab work, and that the most important aspect of what we do is the people our projects affect. I also discovered that research is a lot more multidisciplinary than I expected, and that there are a lot more different kinds of work involved than just traditional wet lab. Additionally, I realized that not everything happens at the pace you hope or expect, but that the process and the results, whatever they may be, are always important and always have an impact, even if it isn’t the one you were expecting.