A Boolean Model of Microglial Phenotype Transitions Under Acute and Chronic Inflammation

May 1, 2020   /  

Student: Bao Chau Nguyen
Major: Neuroscience
Minor: Environmental Studies
Advisor: Dr. Erzsébet Ravasz Regan

Bao Chau NguyenInfection or damage to neurons can trigger the activation of a specialized class of brain-resident immune cell, microglia, which clear infection and help tissue repair. The persistence of microglial activation beyond an acute infection response contributes to many age-related diseases like Alzheimer’s and Parkinson’s. Depending on the nature of neuronal insults, microglia take on an M1 phenotype and secrete cytotoxic mediators, or an M2 phenotype, in which they assist in neuroprotection. Current treatments of neurodegenerative diseases focus on reducing the pro-inflammatory effects caused by the prolonged M1 phenotype. Fewer interventions rely on M2 microglia’s ability to promote tissue repair and wound healing. Here we propose a Boolean regulatory network model that shows the transitions of M1 to M2 signaling and the reverse under acute and chronic inflammatory conditions. Our model offers testable predictions related to environmental factors and specific pathways responsible for microglial morphological remodeling. The results point out the critical role of neuron-microglia crosstalk in regulating microglial activation. Our model broadens the understanding of microglial plasticity in response to different inflammatory signals, which could help diversify therapeutic strategies for neurodegeneration.

Bao will be online to field comments on May 8:
8am-10am EDT (Asia: evening, Africa/Europe afternoon)

87 thoughts on “A Boolean Model of Microglial Phenotype Transitions Under Acute and Chronic Inflammation”

  1. Congratulations, Bao – this is amazing! Thank you so much for sharing it with us. Your fan club now includes my 9-year-old twins … they want you to make a Netflix series because “you make science fun for everyone!” 🙂

    1. Thank you so much Dean Christa, that is actually a very fun idea. I might make a series. Please tell them to wait for me a little bit.

  2. Fabulous video Bao – I saw you on this day, I had no idea what a creative expression of a neuronal model you were about to create! Your detective skills were put to good use, mini Bao cells are incredibly interesting and I like your emphasis that research should focus on how to keep them “happy” instead of only shifting them away from “overly aggressive”. Did your model provide any ideas about how to do that? You mentioned that neurons control the microglia, are there ways to help neurons keep them in check?

    1. Yes we have concluded some molecular and environmental predictions regarding the shift of “happy” microglia to “angry” ones and the reverse. the expression of ARG1 protein via TREM2/DAP12 and IL-4 pathways promote the shift to happy microglia in a post-infectious environment.
      Neurons themselves secrete signals to keep the microglia in check, and I refer to them as neuronal resting signals (such as CD200 or CX3Cl1)
      Thank you so much Dr. Stav for your comments and encouragement. We were filming right on the day we met you. It was the last day I was in the States.

  3. Bao, thanks so much for your work on this important topic and for explaining it so clearly (and with so much joy!). After watching your presentation I saw how each sentence of your abstract translated into a fun and informative section of the video and I understood both much better. And I agree with Dean Craven’s kids!!

    Can you explain more about the implications of your work for existing and future treatments? Is it that current treatments try to suppress the unhelpful functions whereas your model suggests new treatments might try to promote the helpful ones? Thanks!

    1. Thank you so much! I might make a series thanks to the kids’ suggestions.
      For your questions, a popular intervention is the use of non-steroidal anti-inflammatory drugs such as cyclooxygenase (COX) to alleviate the symptoms caused by the angry microglia’s vicious pro-inflammatory cycle. Not many rely on the happy ones. So this model is one of the first steps to see how can we utilize the happy ones instead of eliminating the angry ones only.

  4. Bao,
    I loved the way you used the Digital Studio space to illustrate the concepts of Mini Bao. Impressive molecule modeling too. Best wishes for your future plans.

    1. I always love to make fun videos like this. Your compliments will be great encouragement for my future plans. Thank you again.

  5. This was one of my favorites because I really felt the video explained it so well. Great job!

    1. Thank you so much Reon, I still remember you are the first person from the college that I ever talk to. I will miss you much.

  6. What is a prediction of your model that could be tested by next year’s IS students?
    Thanks for the video.

    1. I have many different predictions for this model that is potential for next year IS students. The most interesting one I believe is to expand this model. Since my model focuses on the molecules secreted by neurons to talk to microglia. I think it would be really interesting to look at the molecules that microglia secrete to talk to neurons.

      1. If you need more details on this and other predictions, don’t hesitate to email me or Dr. Regan.

  7. Bao, Thank you for providing such a fun and clear explanation of your research. I agree with Dean Craven–you have a future in making science fun for everyone!

  8. Congratulations Bao, your video is so impressed and I will stay hours and hours watching it. Thank you for sharing it with us👩🏻‍🎓📚🎓💫

    1. Thank you so much!!!! I feel so happy that you and others are liking the video so much!! I can’t express enough!!!!

  9. Congratulations, Bao! I really enjoyed your video– it definitely highlights your creativity and wonderful sense of humor! I’m curious what kinds of environmental factors does your model use in its predictions?

    1. Thank you so much Mae, I have a resting, an infectious, post-infectious, and a chronic inflammatory environment for this model.

  10. Thank you for your research and the video explanation.. What would the next steps that you feel should be explored based on your research?

    1. Thank you so much Lori, there are many directions I can look at. One of them can be looking at these microglia but on a population level. The current one is only a single microglial cell.

  11. I could have never asked for a more phenomenal IS student, thank you for a fantastic year — and let’s publish this!!!

    1. Yes Dr. Regan, you are the miracle I need to finish this challenging but extremely exciting project!!

  12. Bao, I was so impressed with the creativity you showed in the way you presented this project. A great reminder that scientists need to be able to explain their work to others. Congratulations!

    1. I hope you are doing well Dr. Clayton, it was inspired from my time studying abroad if you remember.

  13. Congratulations, Bao! I love how your enthusiasm for your topic comes through in your presentation.

    1. this IS has been a great journey for me. Thank you so much for your support!

  14. Congratulations, Bao! You are so creative and humorous. Very well done. Best of luck!

  15. What a great video! Such a nice way to explain your research, especially for a non-scientist like me. Congratulations on all your hard work and this significant accomplishment! Way to go!

    1. I am so glad to hear that from you!! My passion is to transform research like this into fascinating video or animation!!

  16. Bao – thank you so much for sharing your research and your creativity! It takes a great deal of skill to communicate a very technical project in ways that all of us can understand. I wish you all the best!

    1. Thank you so much Krista, thanks to APEX, I gained my video skill while doing an APEX internship in my third year summer!!

  17. Congratulations, Bao! Thank you for making your complex research accessible for all of us. I hope you have the opportunity to teach someday; you clearly have a talent for explaining complex ideas! I wish you all the best in your future endeavors. I’m sure your parents are very proud.

    1. I am actually applying jobs for teaching!!! That is very encouraging for mee!! thank you so much!!

  18. Hi Bao! This is so wonderful! Thank you for finding your authentic voice and sharing this with us! While neuroscience is complicated, you did such a wonderful job of explaining it to us 😊. My question is: how do you envision this modeling to be adapted on other systems within the brain?

    1. I miss you so much Justin!! Yes this modeling can be expanded on a population level where it interacts with other cells rather than just neurons, such as astrocytes, another team player for the brain immunity!!

  19. You make me fall into science again!! Love you forever from your hometown! Moa

  20. Bao, this is a fascinating topic. Two of my elderly family members suffer from Alzheimer’s and one from Parkinson’s, so it was interesting to learn of this contributor to those conditions. Your video is wonderful. Your use of humor to convey your complex and important work was genius. You are talented not only in neuroscience but as a video star! Congratulations on this culmination of your years at Wooster!

    1. Thank you so much Dottie!! I wish we could have worked with each other longer! I hope you and your family are doing well!

  21. Congratulations, Bao! So well done! Thank you for sharing your knowledge and creativity simultaneously. Best wishes for the future!

  22. Well done, be Bao! You never cease to surprise us with your endless creativity.

    1. Hu thank you chị Khuê ơi, thank you for supporting me!! Em luôn coi các anh chị là tấm gương huhu!

  23. Congratulations chị Bảo nhaaa!!! The acting is brilliant; I just have to say that again!

    1. Hu cám ơn em trai nha, viết tên em cho Lavender celebration nhưng k biết có được celebrate không nữa

  24. Amazing job Bao! I know how hard you worked on this, and your efforts truly paid off. I’m so proud of you!!!! Also the video is great, it explained everything so clearly. Congratulations!

    1. I think you are one of the people that really saw me when I was so stuck while doing my IS. Thank you for being there and always supporting me. Thank you so much again Alena.

  25. OMG congratulations!!!! This is just straight-up amazing!!!! Chùi ui chị iu giỏi quá hà!!!

    1. Hu em tui ;__; giỏi gì đâu em ơi!!! Em sắp tới rồi đóaaaa

  26. Well done! The visuals in the video really helped us to understand the concept and research. How creative!

    1. Thank you so much!! I tried my best to make it easy for my parents to understand!

  27. Can I just ask you not to call me a “copy cat” when I follow a similar format next year for my IS haha? This video, the content, your energy, and creativity are all amazing. I’m so glad we met at the lib. I really enjoyed working with you and so happy we can keep in touch in the future as well!!!!

    1. It was my luck to be your friend!! I would love to see yours too!! I really admire you, Alayt!!

  28. What a wonderful communicator you are. Did you perhaps develop these skills in any particular class??? 😉

    1. haha definitely from Dr. Mariola’s classes!!! I think you should make the presentation-intensive a thing at COW!! Especially in this time of online videos like this!!

  29. Delightful, inspiring, important. When I first saw your video on the College’s social media I forwarded it to friends as a great example of the creativity, enthusiasm, purposefulness, and collaborative mindset of CoW’s young scientists…and because it was such good fun! 🙂 Congratulations, and my best wishes for all of your endeavors.

  30. Bao, what a wonderful video! Great work on translating your research for a general audience with humor and creativity. As you go forward with your research, I hope you will also have the chance to keep writing and making art like this. It was a pleasure to read your creative writing and I’m bummed that we never managed to meet up for coffee before quarantine. Please stay in touch!

    1. Hi Dr. Beutner, I am so glad to hear from you!! You have helped me a lot in exploring myself and putting my creativity into my work and research!! It was such a crazy semester this time and I am sad we couldn’t talk more about the Vietnamese character. We definitely should stay in touch! Hope you are well!

  31. Bao, your research on its own is impressive, but this video is incredible: it’s creative, informative, engaging, and accessible. Thank you for sharing your project in such an entertaining way!

  32. Wonderful, creative work here, Bao–your video does a terrific job of explaining your research as well as its importance! I’m sharing this with my research assistants so they can be inspired for their own IS projects.

    1. Dr. Hayward, that is so exciting to hear that my video can inspire others!!

  33. Congratulations, this is great. I’m so happy that you shared your intelligence and your personality with everyone. This was a wonderful project. You are going to do great things no matter what path you decide to take. Wherever you find yourself, be yourself and you will never fail. So proud of you!!

    1. I hope that the next path I take, I can truly find myself too. You are the best boss in this world!

  34. Such a fascinating project Bao. I especially loved your video! All the best to you!

  35. Fantastic! Really enjoyed the presentation and glad to see that you got Todd involved as well! Congrats Bao!

  36. I absolutely love this video! You deserve a lot more recognition. It is very inspiring for me as I have been trying to improve my native language skills in order to explain my future I.S. to my grandmother! Wish me luck. Also, your study was AMAZING and so very important. Great job, Bao! I wish you the absolute best 🙂

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