Dr. Frank Grosveld discusses distal interactions in the genome and how these might be less directed than generally thought.
Long Distance Relationship in the Genome
Well, I’m most excited about something that I have been working on for a long time. Which is basically how bits of the genome interact with each other.
So we know that control of genes takes place over a long distance. It can be up to several hundred kilobases. So it’s quite a bit.
And we don’t really understand how these particular fragments or sections interact with each other. We know a bunch of the proteins that bind at such location. But we have no idea why they actually make a loop and would interact with each other.
And of course, we now know the whole genome is looped. It’s one loopty-loop, so to speak. It’s still coming up, but we’re talking about the changes that take place at such regions that may influence the sort of interactions that I’m talking about.
“But we have no idea why they actually make a loop and would interact with each other”
And one of the intriguing possibilities is that when things interact with each other, it’s not because they have so much specificity for each other, they like each other to bind. It could just be that they form almost a colloidal fluid, which is, everybody knows, the dressing on your salad. Oil and vinegar. You shake it, you get little drops of oil or water inside the other phase.
And perhaps proteins, when they bunch together, appear to be doing something very similar in this nuclear environment. And so it sets up a very intriguing situation as to how much of this is really directed, and how much of it is just because you dare, it happens, so to speak.
Lots of people, I think, are very much taken in with the idea that everything’s directed and programmed. And I quite like to think about the opposite, is that it’s very much fortuitous, so to speak. And if it works, you keep it.
So that’s, for me, a very exciting area. And what’s most intriguing about it is the dynamic situation of that. So when two things interact, we know that they fall apart again. And so it’s a continuous binding and non-binding or interacting and non-interacting.
And of course, different cells do different things at the same time. So what you see in one cell will not be the case in the next cell, even though the cells are the same in terms of what they look like. So I’m very interested in this dynamic situation.
And perhaps one of the biggest challenges actually, is to visualize the process in action. Now that’s very much dependent on our technical abilities, and I hope we’ll get to it. But for me, that’s one of the very exciting areas of this type of research.