David Clayton

Transcription

Now in the case of songbirds, which is what I work on as a model organism, some of the things that are really highlighted by songbirds that are relevant to humans certainly are, for example the ability to communicate through learned vocal signals. Songbirds learn to sing by listening to a tutor when they are a infant or juvenile bird and they listen to their adult tutors and they gradually come to copy the sounds that their adults make. In fact this process of vocal imitation really has no other parallel in the animal kingdom other than human beings. And so if you’re looking for a model for how does a human being learn to communicate through language and so forth there is no better animal model than that of a songbird. Now songbirds have other features as well that have made them into an interesting model organism. They have these very distinctive differences between male and female, the sex differences in the brain have been a focus of a lot of research. Again, we think this is highlighting something that is relevant to humans but that is especially drawing a stark contrast in the songbird. Now because it’s an experimental model organism we can go in, take measurements in the brain of a living songbird, which again makes it a powerful experimental organism. In fact the diagram in the back shows the work we’re doing here at Beckman to try to enhance our ability to monitor what is going on in the brain of a living bird as he sings or as he listens to some song. You see this is a little zebra finch here, this is his beak and his eye but this whole apparatus here is a little helmet that we have constructed. We actually do it with a 3 dimensional printer that lays down this component resonance in layers so we use computer automated design to fit this thing. The whole purpose of this really is to actually allow us to use this as an anchoring point to attach fiber optic cables that are used to send and receive light signals into and out of the brain. And the work that we are doing in collaboration with Gabriella Gruton(?) and Monica Fabiani here at Beckman. We are analyzing light signals to gain insight into what’s happening inside the brain while the bird is wide awake potentially, ideally while the bird is singing and interacting and listening to songs. So it’s the ability to do these kinds of manipulations and to relate it to things that we know about anatomy inside the head and genes that are expressed, and things that we can study invasively in the songbird, we can also make that bridge back to humans through these noninvasive kinds of techniques. Hopefully, we develop measurements and so forth that have applicability to processes that are put on the human brain. So in the case of the FMRP, or the Fragile X Middle Retardation Protein, story, that’s a gene that has been implicated, as the name says, in mental retardation. But we don’t really understand necessarily the mechanisms by which it causes it. One of the other symptoms of the disorder in humans is a major disruption of ability to speak. So investigators, as we have developed the kind of genetic and genomic tools for the zebra finch as a model organism, it’s now become possible to ask whether or not that same gene, the fragile X middle retardation protein gene, whether or not that same gene could also be having a role in the development and function of the songbirds nervous system that’s controlling this property of vocal learning and vocal communication. Stephanie Ceman, here at Illinois and here at the Beckman group has led a project to try and identify the songbird or the zebra finch version of the fragile x gene and she has been successful at that. So the vision there is that ultimately we again may be able to take advantage of the model organism properties of the zebra finch to study both what might, how a disruption of FMRP gene, how that might lead to a disruption of speech and communication and so forth and potentially also what we might be able to do to fix that disruption. So for example, the idea would be that we would now be in a position to target the FMRP gene and try to disrupt it using genetic techniques and so forth in the zebra finch to see whether or not this does develop, does disrupt the process of vocal communication and vocal learning. In two other cases, we and other colleagues have done this kind of thing sort of proof of concept, and have shown that if you disrupt key targeted molecules, the bird does not learn to sing properly. One of the things, I think, that we can learn from studying songbirds is that it’s not just one gene and so there are, as I mentioned a minute ago, when a bird hears a song - we spent 15 years studying one gene because we found that this one gene gets turned on and turned off when a bird hears a normal song – more recently, now using more kind of high technology approaches of modern genomics. We’re finding there are hundreds of genes that are being turned on and off. So part of the challenge for us, I think, right now is how to deal with this problem of complexity, of you know - when we’re looking at a complex nervous system, complex genome, and many different interacting components. And yet at the end of the day, what we care about is mental retardation or loss of brain tissue in aging and degeneration and so forth. We’ve tried to connect the dots between all these complex things and these very simple and immediate problems that humans can experience. This is our challenge; the Beckman Institute has again a long history of trying to confront this problem of complexity in biology, so this is a good environment for thinking about this problem. Well it obviously would be enormously gratifying. When I started in science, I was weighing whether I should go into medicine or into research. And I made a decision that I wanted to do research but that had always been motivated by a sense of social responsibility. Some of the questions that motivated us are pure intellectual curiosity about how the world works but there’s absolutely no question that nothing would make me happier than to see useful applications come from this. Certainly, my own research has been supported now for 20 years by the National Institute of Health, the NIH. So I feel I have a big debt to repay if you will. Like everyone, I have friends and family who have suffered from Alzheimer’s disease and Parkinson’s disease and psychiatric problems. This is certainly the context that the work in centered towards.