The Circuitry of Immunity

I’m sure the last thing anyone wants to read about right now is more immunology. A lot of people (myself included) have thought something like this at least once in the past few months: “If I hear the word ‘antibody’ one more time, I will walk out of this room right now.” Well, the bad news is I’m still going to be talking amount immunology, but the good news is my research has to do with a different kind of immune system! While antibodies are essential to fine-tuning humans’ adaptive immune response to very specific pathogens, there is another, broader kind of immune system called the innate immune response. The innate system recognizes general biological traits associated with pathogens, like glycan (a component of many bacterial cell walls), unlike the very specific adaptive system. Given the recent explosion of coverage concerning antibodies, it would be easy to think the innate response is just irrelevant, but that wouldn’t be doing justice to the evolution and ubiquity of innate immunity. Immunologists and developmental biologists discovered that innate immunity is way older than adaptive, and is present in a vast array of organisms compared to adaptive immunity, which is really only present in vertebrates (that’s us!). Because adaptive immunity likely evolved from the innate response, it also means that the two are far more interconnected than anyone previously thought.

Because the innate system is so old, it’s had a lot of time to diversify the molecules and cells involved, making it hard to draw evolutionary connections between the immune systems of humans, which have both innate and adaptive immune systems, and those of sea urchins, which have only an innate system. So instead of looking only at the kinds of immune cells and molecules produced, essentially the “end results” of immunity, developmental biologists and immunologists have turned to gene regulatory networks (GRNs) that determine when and how these immune cell types develop. Through these GRNs, we can better understand both how immune systems evolved and what role each gene plays in immune cell development and function.

Recently, the McClay Lab discovered a gene that is very highly expressed in a certain cell type of the embryonic sea urchin innate immune system. There’s also a kind of “master signal” at the beginning of sea urchin development which has been really thoroughly investigated over the past couple of decades. My work in the McClay Lab this summer focuses on finding out if there is a significant connection between this original “master signal” and this specific “end product” gene in the immune cells. If the genes can affect each other, it means there is probably a GRN connecting them, but we have very little idea of how many gene components are in the circuit, what they are, or what they do – all out there to be discovered. If there isn’t an observable connection between the master and end genes, then the end gene could be the tail of a completely unexpected GRN, which poses an equally exciting opportunity for research and discovery! I’ll be using a battery of microscopy, molecular biology, and moving-colorless-liquids-back-and-forth techniques to get at this GRN, and probably producing some really cool pictures of colorful embryos along the way (stay tuned)! Although this project may seem daunting, characterizing this genetic circuitry could help us better understand the incredible harmony between diversity and unity in immune systems across all domains of life, and provide some really awesome insights into how to analyze rapidly evolving biological systems, like the immune system. The past week working on this project has been a complete joyride, and I can’t wait to keep it going through the summer!

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