Marcel El Kouri

Double, Double Toil and Trouble: Using Fruit Flies to Understand Intellectual Disability

April 10, 2021   /  

Name: Marcel El Kouri
Major: Neurobiology
Advisors: Dr. Seth Kelly, Dr. Laura Sirot, Dr. Erzsébet Regan (second reader)

Intellectual disability (ID) impacts millions of individuals worldwide, and is often caused by single gene mutations that disrupt typical brain development. Scientists have gained stronger understandings of the molecular activities of these mutations by researching neurodevelopment of the common fruit fly. These small creatures may look very different than us, but actually share numerous biological pathways to humans, especially regarding axon development. This video presentation focuses on human ZC3H14, a gene that when mutated often leads to ID, and the fruit fly version of that gene, dNab2. Previous work suggests mutations to dNab2 result in axon overextension, but little is known about another gene dNab2 possibly regulates, dArc1. Does dArc1 also play a role in axon maintenance? Or could dNab2 and dArc1 cooperatively regulate axons? This study established three mutant fly lines – dNab2, dArc1, and double mutants – and examined the developing larval brains from each group. dNab2 mutants displayed overextension as expected, and both dArc1 and double mutants displayed a visible separation between certain axons. These results support previous evidence that dNab2 is needed for axon guidance during development, suggests dArc1 does not directly impact axons, and hints at a possible interaction between dNab2 and dArc1. While ID and development are complex topics, my hope is that anyone can watch this presentation and gain a greater appreciation for one of the most widely used tools in neuroscience…flies!

Marcel will be online to field comments on April 16:
2-4pm EDT (PST: 11am-1pm, Africa/Europe: evening)

107 thoughts on “Double, Double Toil and Trouble: Using Fruit Flies to Understand Intellectual Disability”

  1. Great presentation and communication, Marcel! Congrats on what is clearly a job well done.

    1. Thank you, Professor Feierabend! And thank you for your support during my time at Wooster, it truly does mean a lot to me.

  2. Hi Marcel!! Congrats on completing an awesome IS!!! Which part of your research did you find most surprising?

    1. Thanks Rachel! I think the most surprising aspect of this work was that my control group reflected the overextension normally seen in the mutant group…when I first saw that, I was laying on the floor for an hour laughing at how that could have possibly happened!

      If I had more time, I would love to tweak this protocol and try and improve how we were preparing brains for imaging. I’m certain the control flies aren’t showing overextension that frequently, we just need to improve our methods.

      Also – very shocking how quickly you can pull a brain from fly larvae. Not sure if that counts as a good “fun fact” when I introduce myself to people.

  3. PARABÉNS PRIMO MANDOU MUITO!!!!
    A FAMÍLIA AQUI NO BRASIL TA MUITO ORGULHOSA!!!!
    É FESTAAAA

  4. Absolutely fantastic presentation, Marcel, thanks for sharing your work in such an accessible and engaging way!! Your passion for communicating science to a broad audience definitely shines through. I’m incredibly proud of you, and absolutely cannot wait to see what you accomplish next! Congratulations!!

    1. Oh how I miss you Emma! Thank you so much for your kind words. I’m certain we’ll be able to meet up again soon. In the meantime, I’ll keep you updated as I make my transition to graduate school.

  5. I’m really sorry, but I still don’t like fruit flies. But I was impressed with your narrative style and “teaching” the audience in an accessible way.

    1. You know how the first time we all got tested for COVID, we were all so disturbed at how far the nasal swab went in our nose? But now that it’s been over a year, we’re somewhat used to it? I feel that way with the smell fruit flies get when you forget to move them to a new vial. They’re an acquired taste. Hopefully you can still appreciate how useful they are for research!

      1. Great job Marcel! The way you presented the project here did a nice job explaining the question to a general audience. Thanks for all your hard work this year!!

  6. Hi Marcel, I really enjoyed your presentation and found it easy to follow along (even though I do not know much about this). I remember you talking about your fruit flies in Neuroscience. Did you have any troubles with them? Or are there any funny stories about the fruit flies that stand out? I remember when I fermented beer, I did not know how much yeast to add, so I put too much and all my test tubes overfilled and practically exploded all over my work area!

    1. Jet!!! Thank you for coming to watch! That was the goal, as long as folks who don’t know much about flies are able to follow along and learn something new, I’m content. Fruit flies themselves are rather easy to care for, the biggest thing is transferring them to new vials with fresh food every week. I’ve worked with fruit flies for I.S., and a summer internship I did at Scripps in 2019. In spite of that, I still cannot successfully transfer flies to new vials without knocking them out. Some scientists can easily turn a vial upside-down, tap it, and drop all the flies into their new home. Whenever I try to do that though, I end up releasing 1/4 of my flies into the lab….oops!

      There have been many instances of me running around the lab trying to catch those flies. Only slightly embarrassing.

    1. Thank you. for watching Emma, and I’m glad you were able to learn something new today!

  7. Congrats Marcel! Thank you for highlighting the importance of fruit fly research and maybe even more importantly, making neuroscience accessible to all. This is a great skill that will serve you well in your graduate career.

    1. Thank you, Dr. Colvin! I’m hopeful it will. Science should be accessible for everyone, because science is meant to serve everyone!

  8. Congrats Marcel!! Your presentation was so engaging and used a conversation like style that makes it accessible for people with large backgrounds in this topic but also people with little to no background. Amazing job communicating your incredible project and science!! I was wondering with what you learned from this project, what follow up experiment you would do?

    1. Thank you so much Rachel, and thank you for being an excellent lab member! I’m very grateful for your support this semester. For future work, I’d like to branch out from dissections and explore the impacts these mutations may have on memory formation during adulthood. There’s some evidence that mutations to dArc1 leads to loss of long-term memory in mice, but we aren’t certain what might happen in fruit flies. I’d really love to test that out more, especially with spatial memory! Why spatial memory? I think it’s neat!

  9. Nice work, Marcel! I really enjoyed your informative and entertaining presentation. Your science communication game is strong! You mentioned that the pandemic affected your dataset, and yet you’ve clearly learned a lot from your work – of all the challenges that you faced in your I.S. process, what are you most proud of overcoming? I’m excited to see where you go from here! Well done!

    1. Thank you Dr. Pollock!

      The pandemic created challenges for both data collection, but more so for my own self-confidence as a scientist. I truly did underestimate the impact COVID would have on my mental health, and as a result I often felt extremely behind on I.S. There was even a period I had to step away from lab during the Fall semester! Now that the work is done, I’m proud of myself for being able to (eventually) ask for help and be kinder to myself. Those are skills that will take me far during graduate school, and in life!

  10. Marcel, I loved your presentation! Congrats! I am so excited to see your future accomplishments.

    1. Thanks Kate! I’m excited to see what the future has in store for both of us!

  11. Very interesting study, Marcel. Was not aware that fruit flies share biological pathways with humans. As more research goes into gene mutation in fruit flies, how will neurobiologists, then, use these findings to better understand intellectual disability in humans? I am curious to learn more about applicability of these studies on human brain development. Congratulations on completing this wonderful project.

    1. Thanks Professor Miyawaki! It’s very surprising to learn we share similar biological pathways with something as visibly different as a fruit fly. The same is true for other species as well, like mice or songbirds! We are drastically different in appearance and behaviors, but our brains often share similar processes for memory.
      For intellectual disability, this research helps uncover the molecular activity of these genes. That way, when mutations to occur, we can clearly explain what has changed in brain to produce an altered behavior. That knowledge is incredibly useful for both 1) empowering individuals and their families to better understand why intellectual disability occurs, and 2) creating potential therapies to address alterations in development before they occur….that being said, that does open up the conversation regarding if we even SHOULD be doing that…
      Personally, I’d really love to see this knowledge be used to create computational models of brain development. Imagine if we could easily visualize how brains development through a computer, and guide future research using that model! Exciting!!

  12. Marcel you are amazing!!!! I am sad to see you go but thank you for giving me an idea for my IS! I am also interested in neurodevelopmental disorders so I was fascinated by your research. Do you think this study could be modified to look at other neurodevelopmental issues such as ADHD? Thank you for being such an amazing ZI! We will miss you!!!

    1. Funny you say that…yes! I actually proposed research similar to that to the National Science Foundation, and earned a Fellowship for my graduate studies. Other RNA binding proteins have been implicated in topics like ADHD and autism. If someone wanted to investigate that topic, they should first see what genes are commonly implicated in ADHD in humans. Then, find the fly version of those genes (the ortholog), and create a mutant fly line! You could examine larval brain development using a similar protocol to my thesis, or examine changes to behavior in adulthood. The world is full of possibilities!

      I’m always an email away! Don’t hesitate to keep in touch with future questions, I’m always happy to help students navigate STEM. Thank YOU for being a wonderful student!

  13. Marcel this is amazing! That you for doing such important work. Can you tell us more about what you will be working on in grad school?

    1. Thank you Miyauna! And the answer to that,…is no!

      I’ll be attending the University of Michigan, and for my first year I’ll be “rotating” into different labs to decide what I’d like to work on for my thesis. Broadly, I’ve been interested in plasticity (especially after stroke) and how the environment can alter our brain’s structural organization. However, I’ve grown more and more interested in the molecular basis of mental health disorders. I’d really love to find a lab where I could research what goes on in our brains to produce such behaviors, and then communicate those findings to the general public. My hope is that once folks understand anxiety is truly comes down to neurons acting differently, we can reduce the stigma surrounding mental health challenges.

  14. Congratss Marcel! – I loved the way you explained the material and how engaging your presentation was!
    Estoy super orgullosa y te quiero un montón!

    1. ¡Y gracias por visitar mi pagina! Estoy muy orgulloso de lo que has logrado durante su primer año en Wooster, y estoy super emocionado de ver todo lo que logrará.

  15. He is very obviously intelligent and creative, but more importantly Marcel is an incredibly empathetic TA/teacher/mentor. His drive to make science inclusive in the aspect of research but also in science education is the most admirable thing about him. He is going to surpass expectations in whatever he chooses to do with the rest of his life. To his future employers- please hire him and give him lots of money.

    1. And she is very obviously an excellent student who will excel in a career in neuroscience. Thank you for your kind words Hannah, and for being an excellent student to mentor! I’m very excited to hear about your future successes at Wooster. Please keep in touch!

    1. Thank you Dr. Sirot! And thank you for your excellent mentorship this semester – it truly couldn’t have happened without your support.

  16. Marcel, you are such an impressive human being that I have no doubt will change the world. Its been so wonderful to hear about your journey with this subject. I admire how you’ve tackled tough obstacles and grown from the challenges! Thanks for sharing this with us, and for being all that you are!

    1. The same goes for you Laney, I’m incredibly grateful to know we’ll be sharing an alma matter soon! Thank you for visiting my page, and for your wonderful message!!

  17. One more question! Are there any other genes that you’d like to study that when mutated often lead to ID?
    Do you think there are other genes like dArc1 that interact with dNab2 in some way and play a role in axon maintenance?

    1. The study I based this project on found that dArc1 was highly under expressed in dNab2 mutants. Additionally, that study found many other genes were down-regulated, including dKmn1 and Xbp1. Both of these genes are known to have interesting impacts on cells and nearby proteins, especially Xbp1 which is implicated in Alzheimer’s disease. I’m unsure if they have any impact on axon maintenance, but they seem to interact with dNab2 to some degree.

      These interactions get complicated very fast, so future work should also look into using a computational model to facilitate research.

  18. This was an amazing presentation, Marcel! Anyone who has the privilege to learn from you in the future will be so lucky. Congratulations, and I can’t wait to see what you accomplish in the future!

    1. Thank you very much Natalie! I really should start printing these compliments for when I need a confidence boost, y’all are making my heart so happy.

  19. What a great presentation and wonderful use of analogy to explain complicated science.

    1. Thanks Jenni! Analogies are my favorite tool for communicating science – the weirder the better!

  20. Congratulations Marcel!! Absolutely loved the presentation on such an interesting topic!!

  21. Hi Marcel, Congratulations! Really great work and presentation. Your time and efforts spent at labs really paid off. I’m proud of you! Wish you all the best in your future endeavors.

    1. Thank you so much Merlin, and the same goes to you! Super excited to see you shine in graduate school.

  22. Great presentation Marcel, I really enjoyed learning about the connection between these genes in flies and their connection towards neuroscience!

    1. Thanks Andrew! Next time you see a fruit fly, be sure to think of me. Especially when you squash it.

  23. Congrats Marcel! Your presentation was funny, engaging, and educational. What led you to your I.S. topic (i.e. why were you interested in looking at intellectual disability)? Additionally, is this something that you will be continuing to pursue at Michigan (yay for more data points!)?

    1. Oh Marloes what an excellent question. You can thank our best friend COVID for that! I was initially planning on exploring spatial learning for my I.S., but time constraints and concerns of a looming shutdown quickly halted progress on that study. That being said, I chose to explore intellectual disability because my favorite aspect of neuroscience is the ability to reduce behavior to the actions of neurons and molecules. Folks with behavior that isn’t as common are not “stupid” or “bad”. They just have different molecular activity in their brain! I’m grateful to have worked on a project that could have contributed to that ideal.

      As for graduate school, I’m not sure yet. I do love using science to reduce stigma, and I’d be interested in branching out into mental health disorders.

  24. Your presentation was excellent and engaging, I really enjoyed watching it. Congratulations and great job!!

  25. This is a cool presentation! I appreciate that you threw in some jokes and made it entertaining, as well as informative. Do you mind explaining how you actually went about creating the mutations in your fruit flies?

    1. In my opinion, more scientists should learn to incorporate comedy into their presentations. There’s such fascinating research out there, but it’s hard to get excited when your presenter seems bored with the work!

      As for the mutations, I used something called “imprecise excision”. Essentially, a wild-type control fly has a “p-element” inserted next to a gene of interest (in my case, either dNab2 or dArc1). Then, that “p-element” is removed from the genome through excision. Sometimes the gene is precisely removed, and we just have another control fly. Other times, the gene is imprecisely removed, and parts of the gene of interest are removed with it! That creates our mutant lines, because part of that gene of interest is now missing!!

      You can learn more about how it happens here:
      https://www.youtube.com/watch?v=ZHqIExTcu0o&ab_channel=AnimatedbiologyWitharpan

  26. Marcel, this is so cool, I actually UNDERSTAND your science! Thank you for explaining your research and findings so well. I’ll be sure to throw other scientists in the fire.

    Congratulations on an IS well written, and your future in Michigan!!! Proud of you!

    1. Woohoo! That was the plan, I wanted everyone to be able to follow along, not just other fly scientists!

      And thank you for being an excellent source of support for me this last year. Very grateful to have met you, and for all that you do for me!

  27. Marcel, thank you for your clear, humorous, accessible presentation of a complex topic–you’re already a fantastic educator! I especially appreciated the running theme of small things (mutations, “nothing” data, fruit flies themselves) having big impacts. Well done!

    1. Thank you Gillian! This might be a side effect of my COVID vaccine, but for some reason I’m tearing up? Strange…

      And thank you for helping me actually write this thesis! You’ve been an writing advisor, and while I’m sad I didn’t meet you sooner, I’m elated to have met you period. I’ll be sure to pick up some Angels Envy to celebrate!

  28. So many brains! Thank you for sharing your research, Marcel — I loved the analogy of RBP’s to conducting an orchestra. Can’t wait to see your future in Sci Com unfold!

    1. SO many brains! Thank you for watching Rachel, and for helping me improve my communication skills through Peer Health!

  29. Marcel, you are my hero. This one comment cannot possibly express how insanely proud I am of you, babes. Congratulations on all of your successes, from I.S. to UM to NSF (god, that’s a lot of acronyms), you deserve it all!
    Every positive word in the English language describes you and I’m so so grateful for your friendship.
    I can’t wait to see you save the world with your bad jokes and your IQ of 476. pARTY!

    1. Stars put in the work, Maya! Thank you for being an incredible friend to me, and for your constant support as I worked on this thesis. Wherever I go, I’ll always carry the joys your friendship has brought me. Right here. I’m pointing to my heart but you can’t see because this is a text message. Pretend you can see it.

  30. Congratulations, Marcel! It’s so refreshing to see how enthusiastic you are about your research. I’m excited for all that is to come for you! One question: what was the most challenging part of your research?
    Wishing you all the happiness in the world!

    1. Gracie!!! Thank you so much!!

      The biggest obstacles for this research (besides my mental health, haha!) was following the precise methodology for this study. Brains are very delicate, so every single step has to go smoothly. One error, and you’ve lost a sample. Over time I got better, but it’s still frustrating to think about nailing the dissection, transferring the brains, treating them with anti-bodies, but then making a mistake when mounting them on the microscope slide. Ugh!

  31. Felicidades Marcel! It was a really accessible presentation and I learn a lot from it! Thanks for being such an amazing example and opening the way for others, te admiro un monton, gracias por todo

    1. Muchas gracias Katiasofia. I’m glad you were able to learn something new! You may be on the cognitive end of neuroscience, but don’t hesitate to look at fly research to guide your own studies. They’re awesome! Estudiantes como tú me dan la confianza de que el futuro será un lugar más equitativo para todos.

  32. Congratulations Marcel!!!! Your presentation was wonderful and I loved your style of communicating science for a broad audience. Can’t wait to keep stalking your twitter as you go amazing things at UMich. Will miss your antics with Dhwani in the lab.

    1. Thank you Shankar! I too will miss our times in the lab. It’s up to you now to keep the lab fun, and to help future students succeed!

  33. Marcel! Such a neat project. As someone who does not have a lot of knowledge in the science realm, I really appreciate how you made sure that everyone could understand your research. Nice work!

    1. Thanks Ellen! I’m glad you were able to learn something cool today. Science is for everyone!!!

  34. Fantastic work Marcel! Being in your presence has always been a delight. I’m very sad that you will not be gracing this campus next semester, you’re a blessing. Also musicians beware, Marcel is out to get you!

    1. Thank you Nosh, the feeling is mutual!

      After this presentation, I’ll be lucky if I’m allowed back into Scheide Music Center…

  35. OMG, Marcel, this is amazing! And, of course, I LOVE the nod to Macbeth. Keep up the great work!!

    1. Thank you so much Dr. Garcia! Your support truly does mean the world to me. I’ll always appreciate the kindness you’ve shown me during my time at Wooster!!

  36. Great job, Marcel and congratulations on your IS! Your presentation is really well-done and entertaining, as always. It’s been great to get to know you over these past few years and I look forward to seeing what you do next (even if it is at that “school up north”). Best wishes and be sure to keep in touch!

    1. Thank you so much Missy! I’m so grateful to know you were an integral part of my Wooster experience. I’ll be sure to keep in touch while I’m working towards my Ph.D. at (REDACTED)!

  37. Excellent research and presentation! Science is meant to be shared! Thank you for your work in science communication.

    1. Thank you so much Dr. Ison! I’m grateful your support, and for the opportunity to learn directly from you. Neuroscience is great, but it’s so wonderful to branch out and explore other passions with excellent professors.

  38. “Brain development is a beautifully played song” – that only begins to cover just how intricate brain development is and the importance of taking time to continue researching it! Such a wonderful presentation that not only changed my opinion on fruit flies but showed me the importance of continuing this research to hopefully develop better outcomes for individuals and shed more light on the topic – who knew a little fruit fly could tell me so much. So proud of you and excited to see what’s yet to come because you deserve it all and you’ve definitely put the work in for it – don’t let that imposter syndrome get to you!

    1. I.S. projects really do help people grow – both the student, and the audience! I remember your I.S. project helped me better understand my own identity, and now my project has helped you gain a greater appreciation for neuroscience! I will do my best to keep fighting the imposter syndrome. Thankfully, I have wonderful friends who help me squash it 😉

    1. The feeling is mutual Angela. From ARCH to Symposium, I’m filled with joy to have met you!

  39. Marcel!!! Congrats!!!! Thank you for being an amazing teacher and mentor over this semester, and how impressive that you managed to accomplish such a huge project while also being there to support us and specifically showing me that there is so much more to science than facts and figures. I appreciate you and everything you’ve done for me and my classmates, I’m going to miss zone hours with you, please don’t forget about us when you become a crazy successful and famous scientist 🙂

    1. This is why I’m so happy when students come to the STEM Zone! I’m very appreciative of your constant commitment to your education, and for your words of support. I will never forget about students like you – y’all help me grow just as much as I help you.

  40. Congratulations Marcel!! I loved your presentation, you nailed it!! I wish you the best of luck as you work towards your PhD – – I feel that if anyone can do it well, you can!!

    1. Thank you so much Syd!! I am a little nervous about going to graduate school, but I want to remind myself that if wonderful people like you believe in me, then there’s no doubt I will succeed!

  41. This is so impressive Marcel!! I am not a science person at all, but I can tell that you really wanted to make your presentation accessible. I appreciate all the musical metaphors! You did an amazing job!! 😊

    1. Thank you so much Eliza! Folks like you are the target audience. You don’t need a bachelors to have an appreciation for science 🙂 thank you for your kind words!

  42. Dear Marcel, What a terrific presentation!! It was so welcoming, and I learned a lot… you do a terrific job of inviting people into discussions of complex information and helping us realize that we are capable of “getting” it! I am going to keep thinking about that piano player….

    Congratulations on your terrific IS, and many thanks for all the wonderful things you have made happen at Wooster. There is so much that you have done that will last here, making life better for generations of students that follow you.

    Wishing you all good things for your graduate work and beyond!!

    1. Thank you, President Bolton! I am slowly (but surely) internalizing my accomplishments, and learning to be proud of myself as well. I’m extremely grateful to have come to a place like Wooster where I had those opportunities to thrive and support others. Thank you for finding the time to support students directly, your words truly mean so much!

      I’m sending the piano player a “Get Well Soon” card. Followed by a “I’m sorry I’m the reason you’re not well” card…

  43. Congratulations Marcel!! This is such a fantastic topic and I absolutely love the title. I cannot wait to see what you go on to achieve in your post-wooster life!!

    1. Thank you Georgia! The feeling is mutual, and thank you for being a constant source of joy on campus these last few years!

  44. This is an amazing presentation! Great job explaining such a complex topic in a way that can be understood by most. Oh, and thank you for the entertainment. We were engaged throughout the entire video!

    It’s great to see all your hard work – those sleepless night and stressful days – come to fruition with the completion of your IS and this chapter of your life. You should be extremely proud of what you’ve accomplished thus far.

    We’re excited to see what the future has in store for you. Phenomenal work, Marcel!

    1. I wonder which one of the Elkouri’s could’ve written this? Papi? Mamãe? Maybe it was Laffy. Regardless, thank you so much for providing me endless support over my undergraduate career. Your unwavering love really does mean the world to me, even if I don’t always show it. I love you all so much.

      I’ll be home soon, and we can all cook our favorite meal together…mexido!

  45. Marcel — it’s so wonderful to see your hard work come together in this way. Thank you for always being supportive of us as staff. Congratulations on your NSF award. Go Blue!

    1. Of course, Dean Hernández! Thank you for showing me support as a student, and as a young adult just trying to figure things out. Go Blue!!

      Apparently their other color is maize….corn? I prefer old gold 🙂

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