Mohamed Jimale

Abstract: Autism spectrum disorder (ASD) refers to a collection of neurodevelopmental disorders phenotypically characterized by social deficits and restricted, repetitive behaviors. While multiple studies have shown ASD to be highly heritable, only 30% of ASD cases have been attributed to a specific genetic cause. We set out to identify additional genetic causes of ASD through whole genome sequencing (WGS) in a consanguineous familial cohort with ASD. We combined WGS with homozygosity mapping and regulatory element annotations to identify candidate ASD variants. We filtered candidate genes according to previous disease association, brain expression levels, evolutionary conservation, and for non-coding regulatory variants, brain specificity. I designed primers and performed Sanger sequencing for 31 candidate variants (including novel candidate genes CHD5 and GRB10) and was able to validate 30/31 (~97%). To test the functional impact of a subset of those variants, I designed CRISPR/Cas9 guide RNA and donor sequences for future transfection into a Neuro2A cell line and subsequent qRT-PCR and western blot analysis. 

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What does research mean to you? 
To me, research is the expansion of the frontiers of medicine; the discovery of a new region in the map of medical knowledge and the subsequent exploration and charting of it. How does the discovery of this region affect how we used to look at our “medical map”? What new tools, resources, and creatures will we discover in that region? By adding to the vault of medical knowledge, researchers give clinicians new weapons in their fight against disease. We often say that clinicians are heroes, and while that’s very true, it’s researchers that give them their “superpowers”.
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Tell us about your journey.
Growing up in the “internet age”, I subconsciously developed this belief that all my questions were only a google search away. We’ve all grown very accustomed to having the answer to all our questions at our fingertips, so you can imagine the reality check I experienced after gaining my first position in a lab (prior to Green Fellows). That experience changed my view of research and medicine in general, and made me appreciate how much there is that we simply don’t know! Being a Green Fellow gave me first hand exposure to the painstaking labor of cultivating knowledge and the disappointment of a fruitless harvest season. More broadly, it gave me newfound appreciation for the sacrifices and struggles that the scientists (whose names we hated being tested on in high school) that came before us went through and how much it took for us to live the life we have today.

What was your favorite part about the program?
My favorite part of the program was the independence and creative freedom we were given in the lab- almost as though we were already graduate students! While this independence was challenging at times, it was definitely satisfying to be a trusted part of the team!

What was the biggest thing you learned from the program?
Research is not nearly as exciting and thrilling as I painted it out to be in my answer to the first question. It’s easy to start thinking pessimistically after an experiment doesn’t go the way you’re hoping, but always remember that there’s never such a thing as a “failed experiment” in science! In fact, the journey to figuring out why your experiment didn’t go the way you expected could very well lead you to a new discovery!

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Advice for Future Green Fellows

​Always try to figure out your “why” questions independently. It’s understandably very tempting to beeline towards your PI the second you have a question that a normal google search couldn’t answer, but there’s really nothing like the satisfaction of independently realizing why your PI designed aspect X of your project in the way they did. It’s incredibly useful to look through past research (hint: look through the references section of your lab’s previous publications on the topic!) to understand the series of questions and discoveries that led to the question you’re trying to answer now. The insight gained from doing this early on will help you make independent decisions on how to proceed with your project when you hit a bump, and will overall make you sound smarter when you talk to your lab mates ;)

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