Rundown 3 — Immune system epigenetic “life diary”

54:20story that we did last week in the rundown. A lot of great animal animal science stories. Uh we're now going to talk about immunology and the debate of nature versus nurture. As scientists discover how life experiences rewrite the immune system, it's like we have a molecular diary of our past. Yeah, this is an incredible story out of the Sulkq Institute in La Hoya, California. Um right out of um right outside of UC San Diego. It answers this question of variability which is something that is very familiar to us having gone through the co 19 pandemic. Some people got completely wrecked by co 19 when they got it. Um other people were fine you

55:02know even with the vaccine on both ends right even if you control for those who are vaccinated and not the variability between responses from one individual to the other is extremely different. Okay. And this particular paper is trying to answer that question. Why are why is stuff so different? They focus on something called the epiggenome. The epigenome is how the DNA gets expressed. Everybody has the same DNA effectively, but like how each DNA strand, how the genes in that DNA get expressed is part of the epiggenome. And that's a very dynamic thing that can change as we age and has as we have life experiences. >> Um the genetic patterns can be changed

55:45through two ways. Either it's a genetic thing, right? Like there's part of our epigenetics where the cells pick which genes to express and which genes to not based on the genetics themselves. And then there's another one where our life experiences actually change genetic expression. Right? And those competing factors are very much in play when it comes to immune cells because immune cells have to learn throughout the experience of an individual. Right? I get some disease, my immune cell has to now remember what that disease looked like me mechanistically so that we don't get that disease in the future. Right? So immune cells are this really great lab to try and figure out what are these

56:25competing effects like. Okay. What they focused on was something called um differentially methylated regions. Basically you've got your DNA strand. >> Your body your cells put tags on the DNA with these things called methyl groups. Okay? And that sort of gives them a distinction between hey this is a methylated piece of DNA this is not a methylated piece of DNA. So structurally from a molecular level they can tell two bits of DNA apart. Okay. What they looked for is how these differentially methylated regions were tied to things like genetics and life experiences. And what they found was there's actually two different types of markers

57:07>> in our genetics. Okay. The part that's more genetic is actually particularly in longived immune cells like the T- cells and the B cells. These are the ones that have memory of our past immune attacks and things like that. And all of these methylated regions are found in the stable regions of our genome. >> On the other hand, if you have things like um you know the killer tea cells, these are the ones that are rapid response. those are the ones that have this methylated region in more flexible regulatory regions. Okay? So you've got these two different effects. And so what this kind of self-sp specific database can tell you is new insight into how

57:49immune responses form and also later on we can do, you know, future treatments that are tailored to each person's unique biology, right? because their particular immune system is going to respond in a different way to somebody else based on their past treatment. So if we can read the epiggenome, we can then forecast how is someone going to respond to a certain treatment, how is their immune system going to respond. That's the idea. >> This is very fascinating. The the the concept here being there are uh you know our genome has both these like genetically uh inherited from long the long history of evolution that then formulate into these long lived T- cells

58:30and B cells which kind of makes sense. It's like oh these are things that for millennia for generations have been helpful so we can kind of memorialize it in our long-term memory. And then there's the sort of the sort of like epigenetic layer which is more about the lived experience of the individual or its most recent >> predecessors uh impact the killer tea cells and these sort of aspects that might need to be >> more reactive to real time stuff in the environment. Um, and so the point >> and we're able to now in the molecules see the difference >> the different how they're tagged between coming from this long history versus a sort of short history.

59:11>> And again I mean this goes to the importance of uh like genetic diversity and clinical trials as an example which is a space that my mom works in because you will have different responses. Yeah. based not only on, you know, someone's African versus African-Amean, but even that, even if they're both black, >> the epigenetic layer of the experiences are going to be fundamentally different between those who are part of the African uh African slave trade versus Africans who are not, >> just as a use case example. Um, and so these kind of details are important because it >> especially as someone who's black, like the medical system and us being able to get treatment is a very complex issue.

59:53>> Yeah. Um because just like photos and film was initially created for only white people, right? And there's fundamental things about the way that film like actual film works because of light. If you think about how light bounces off of white people's skin versus dark people's skin. So until we got later into digital like it was never really made for black people. medicine kind of has a similar issue where a lot of the genetic profiles are have been or the way in which we've operated is for a particular group set and I think as we continue to do this type of research it will allow us to expand the efficacy of medicine across a larger swath of genetic profiles. So fascinating story

1:00:34um >> again there on talking about immunology which has been an issue we've tal a subject we've talked about quite a bit on the pod. >> We're going to move on to origin of life. >> Yeah. for our last rundown story or >> second to last. >> Sorry, second to last. >> Sorry, I want to do I want to do five this time. Sorry. >> Okay. Okay. Uh so for our second to last, which is going to be this um scientist finding genes that existed before life on Earth.