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Base Pairs Episode 9.5: Redefining biologists, redefining genes

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Set aside your notions of how biologists are born, or what the word “gene” means as you listen to our first chat episode. We talk with Assistant Professor Molly Hammell, a genome biologist who started out as an astrophysicist. She tells us what it’s like to peer deep into space using a high-tech telescope. We also speak with Professor Tom Gingeras about whether it’s time to redefine the gene.

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BS: Okay, hey everyone I’m Brian.

AA: I’m Andrea.

BS: And this Base Pairs but-

AA: A little bit different from the Base Pairs that you’re used to.

BS: Ah, yes, just a tad. This is going to be a mini-episode, is what we’re calling it.

AA: Yeah, because these are just a couple little tidbits from the interviews that we did in the previous two episodes. Those were our Dark Matter of the Genome series.

BS: Part one and two.

AA: Yes. And even though we had two episodes all about that, we still had parts of these interviews, as we do every time, that we really enjoyed but just didn’t make the cut. And we wanted a way to share those with you anyway.

BS: Right, right. Some of these moments are going to be, they describe more about our guest’s backgrounds, their history, some really cool tidbits like that.

AA: Yeah, sometimes that’s takes the form of a tangent about their philosophy about what they study. Or sometimes it could just be an anecdote about what got them into science as a youngster. All those little nice moments.

BS: And surprisingly, scientists usually don’t like to talk about themselves, so when we say that these are gems that we want to share with you, they really are. They’re rare moments. Along those lines, I know that you were talking to Assistant Professor Molly Hammell for episode eight, part one of our two part premier. What did you guys get into talking about that didn’t make the cut?

AA: One of the things that I had to ask her about was the fact that she started her career in science as, not a biologist, but an astrophysicist. And that is something that I personally do not know very much about. My science background is all biology, and I wanted to know what it’s like to be a professional astrophysicist, and to use a really fancy telescope.

When you were doing astrophysics, what kind of things were you doing? I’m so curious just such a unique background.

MH: No, yeah, sure. I used to go, so how I spent my time is probably the easiest way to do it. I used to go a couple times a year up to a telescope and I would be alone of a mountaintop, sleeping during the day, staying up all night taking pictures of the sky. And what we were really doing at the time is we were looking for the oldest galaxies in the universe, right. Because we knew, that if we knew how older galaxies looked compared to the modern ones like the one we live in, then we might have a better idea of how our universe formed, and what, how our galaxies derived as compared to the early ones that first formed. That particular property is really determined by the amount of matter in the universe. So the dark matter content has a huge impact because it interacts gravitationally with, okay, this is getting too detailed. I’m going to stop. Okay, let’s start this over again.

AA: And what kind of telescopes were you looking through?

MH: These are professional telescopes. These were, the one I was working with was about three feet in diameter, and then there was another one that was nine feet in diameter. There’s no eyepiece to in the back of the telescope. The telescope sits in its own room, and I would sit in the control room next door and control it from there. Basically just open and close the shutter as many times as possible to cram every image that I could into the night.

AA: So Brian, you talked to professor Tom Gingeras and it turns out, and I did not know this, but he had a pretty strange path to science too.

BS: Yeah, a little bit different than Molly in the fact that he didn’t stick with this for long, but when he was in college he originally was an economics major, and he was pretty far down that path when he sat in on a few biology classes and that was the moment that he realized that he needed to change everything he was doing.

TG: When I was in college, I found myself with some spare time and I sat in on a freshman biology course. Mainly because in high school I never had a biology, and I wondered what that was all about. And it was a such a novel experience, and things I never imagined that we knew about. Needless to say, I spent the next three years making up for the things that I missed as an economics major. Then from then on, it was very clear that doing molecular biology, which was the emerging field at the time, was all that I wanted to do.

BS: Back to Molly though, because I know there’s a lot more of that interview where you asked her some personal questions that tie back to the lab.

AA: Right, things that are actually about biology, which is what we do here at Cold Spring Harbor Laboratory. Yeah, so now that she studies biology, Molly focuses on these strange little zombies of the genome called transposons-

BS: Which you can learn more about in our first premier episode.

AA: Yes, in episode eight, Dark Matter of the Genome part one, and these things were actually discovered right here at Cold Spring Harbor Laboratory by a scientist named Barbara McClintock So I just wanted to get a sense of what that means to Molly, to be able to work at the same place where these things she’s studying every day were first discovered. And to realize how far we’ve come in all these decades.

MH: Wow, so Barbara McClintock, she was an amazing scientist who received a Nobel prize for her research for this discovery. That there are these sort of selfish elements within our genome that are capable of moving around. It was amazing what she did in the time when we had far fewer tools to look at these things than we do now.

Fortunately for me, I have a lot of tools to look at these things that makes them completely visible. Now, we can sequence a genome. We can sequence the genes that are being used at any time, in a given cell. And we can just look and count them up and do a bit of math and statistics on that. At the time when Barbary McClintock was working, she was really inferring this huge, vast existence of these transposon sequences without a picture of what the genome itself actually looked like. She had sort of a rough map, but she you know, for the most part, had no idea what was in between the genes she was following. Her ability to infer that these things were present, without being able to actually see them, it’s amazing right. I feel like the work that we do in my lab, where they’re plain as day, out there and its just a matter of counting them up and doing the math. I have a much easier job.

AA: You make it sound so easy!

As we talked about in episode eight, transposons are not exactly genes. But what even is a gene? That’s something that I know Tom has thought about a lot, and has apparently some very interesting thoughts about.

BS: Yeah right. When I was talking to Tom, this was actually something we spent a great deal of time talking about, and I will not able to show you guys the whole conversation today, but we’ll get to the core of his main points. Which is really that, when the term gene was first developed, it was in a time where nobody even knew what DNA was. Now that that term is being reapplied in the genomics age, it’s kind of being misused in Tom’s opinion. He wanted to elaborate a little bit upon that, and you can hear what he has to say for yourself.

TG: Well there are many phenomenon in classical genetics, which while they’ve been explained partially, have never been satisfactorily fully explained. One of these phenomenon is called penetrants. You can look at a mutation in a gene, and that mutation can exist in multiple people. But the effect of that mutation, that variation on a phenotype can be different. You can have a mutation, which in one individual is lethal, and in another individual virtually has no phenotype whatsoever. Now why is that the case?

It’s because, in many cases, is that there are other mitigating factors that control the effect of that mutation on that gene. Those other factors are other genes. They could be protein coding, they can be non-protein coding. That mitigating factor now brings together this idea, in a very solid manner, that a gene, the gene responsible for this is not just one structural unit. It’s the RNA made from that gene plus all of the mitigating genes that have an influence contributing to this phenotype.

BS: Right, right. What would you call a gene?

TG: A gene is a higher order concept. If you think about, in a subatomic fashion, that the element inside of the atom are many subatomic particles, the total of which constitutes an atom. The atom is the gene. The subatomic particles are the transcripts that contribute to the characteristics of that atom.

BS: So that’s it for today guys. Thanks for tuning in. Hearing a little bit more on what we didn’t get to include in our season premier episodes, Dark Matter of the Genome part one and two.

AA: Yeah, and we’ll be back in June with a new full episode. So make sure to listen in then.