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We’re all familiar with the power of smell:…
Date Recorded
October 27, 2015 Science Topics
Health Sciences Transcription
Interviewer: Cracking the olfactory code up next on The Scope.
Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.
Interviewer: I'm talking with Dr. Matt Wachowiak, a USTAR professor of neurobiology and anatomy at the University of Utah. Cracking the olfactory code. What does that mean?
Dr. Wachowiak: The goal is to really understand how the brain figures out what it is that we're smelling. What's happening in the brain when the animal smells that odor, and how does that get translated into some sort of perception and some sort of behavioral output.
Interviewer: Give me some examples. What are some smells that might trigger very different reactions?
Dr. Wachowiak: The smell of good food or the smell of wine generally triggers some positive emotions, some positive responses. We want to drink, we want to eat. Kind of another side of that would be the smell of smoke for example or the smell of rotting food. We get a very different visceral response to that kind of odor.
We want to basically go in the other direction. That's one of the most simple dichotomies that we can make about odors. Of course odors are very, very complex in terms of their perception. There's a huge amount of information that we take out of odor beyond just good and bad.
Interviewer: Why do you think it's important to understand this code?
Dr. Wachowiak: Just in terms of using this as a system to understand how the brain processes information I think it's really important to understand olfaction because it's so complex as a sensory problem. It's very different from any other sensory modality, for example vision or touch or hearing, simply because we're detecting molecules from the air and they come in a huge range of different structures. They're not organized in a very clear way the way light for example is or sound.
It's just a very different problem that the brain has to solve and we don't understand much about how the brain solves that problem. Just as a way of getting new insights into how the brain processes complicated information, I think it's really important to study olfaction.
Interviewer: Give me a sense of the scale of the problem you're facing.
Dr. Wachowiak: This is really one of the challenges with olfaction and why it's one of the most complex senses and still one of the least understood, mammals like mice and rats which have very well developed sense of smell. They have about a thousand receptors. It's actually the largest gene family in the genome. Odorant receptors make up around 3% of the entire genome.
Interviewer: Wow. Really?
Dr. Wachowiak: Yes. But the real problem is what we don't know. We can identify these genes by looking in the genome, but what we actually still don't know for any given gene what odors the receptors actually detect. This is the major problem. So this is one of the goals of our group is to actually do what's called "deorphanization" which is to identify for every receptor what are the odor molecules that that receptor best detects.
It's been a really hard problem just for technical reasons. So one part of our group has really made some important breakthroughs in the last couple of years in terms of being able to screen receptors for many, many odors and be able to identify the odors that are activating particular receptors. That's one important part of the project.
Interviewer: I imagine it's not that there's one odor for one receptor.
Dr. Wachowiak: The receptors can be activated by many odors, another big part of this problem is that there are so many potential odors out there in the environment. The number of compounds that smell, that we can smell is easily in the thousands. There have been some estimates that are orders of magnitudes higher than that in the millions. That's debatable, but the number of compounds that are volatile that receptors might be able to detect is huge.
Another ambitious part of this project is to really screen a fairly large number of compounds. We're going to screen 1,000 different odors across all the receptors. The goal is to first deorphanize all the receptors using this panel of 1,000 odors.
So then we'll have for a given receptor not just one compound that might activate that receptor or one odor, but we'll be able to make or give a spectrum of tuning curve. So this odor works better than the other odor and we can put those in a response spectrum is what we would call it.
Interviewer: But you're taking it beyond that as well.
Dr. Wachowiak: What we need to know is how does the brain process that information. What does that code look like as we get in to the brain. One goal that we're going to work on is to then be able to assign the identity of the receptor to the glomeruli in the olfactory bulb and we can do this in the intact animal.
We have ways of using an imaging approach where we can literally look at fluorescent proteins that are expressed in these cells in the brain. We can look in the intact animal and watch activity happen basically with imaging and so then we can follow what happens as we go from sensory neurons into this first stage of the brain.
Interviewer: Are you tracking behaviors as well?
Dr. Wachowiak: Yes. That's another part of the project. Right now we can identify odors that seem to be intrinsically aversive that the animals will avoid. A great example is the odor for mice, a great example is the odor of predators. Big cats for example. Urine of big cats they will avoid intrinsically. Even a mouse who has never encountered a cat. And of course they're attracted to compounds that are coming from other mice for example. We can map this behavior.
We're studying the olfactory bulb. Certainly the information from the bulb goes farther into the brain into parts of the olfactory cortex and the part of the brain called the amygdala which is thought in many different contexts to be really important in emotional responses and to all kinds of stimuli.
A hope would be we could then look at a given odor or maybe look at a given pattern of activity. Look at a given receptor even and be able to predict what's going to be the innate behavioral response to that and maybe even what's the pattern of activity going to look like in the brain.
The goal is to understand how does the brain understand information. How does it generate behaviors. We need to look at all aspects of that. Again, olfaction is one of the most important senses for driving behaviors in most animals even in most mammals. We're really trying to use that system to get some insight there.
Announcer: Interesting. Informative. And all in the name of better health. This is The Scope Health Sciences Radio.
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Imagine being thrown together with a group of…
Date Recorded
October 22, 2015 Science Topics
Health Sciences Transcription
Interviewer: The National Science Foundation's Ideas Lab turns the grants process on its head. We'll talk about that next on The Scope.
Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research show is on The Scope.
Interviewer: I'm talking with Dr. Matt Wachowiak, a USTAR professor of neurobiology and anatomy at the University of Utah. I had never heard of the National Science Foundations Ideas Workshop.
Dr. Wachowiak: I had never heard of it either. None of the people that were at this workshop in the end had heard of it. Basic idea is that you bring a number of people together who have applied and were selected based on their interest in collaborating with others and approaching big problems, but not necessarily based on preliminary proposals.
You bring these folks together into a week-long intense workshop in which the goal is to form collaborative teams who are going to approach big high-impact questions using an interdisciplinary team driven approach.
This particular workshop was focused on olfactory coding, Cracking the Olfactory Code was the title of it. The major goal was to really understand how the nervous system encodes information about odors, how the brain processes odor information.
The NSF really decided to dedicate a lot of resources to this. They had set aside between $12 to $16 million to fund several groups which would come out of this workshop to tackle this problem. So we've been in a number of these Ideas Lab workshops for different areas.
Interviewer: And at the end, it's not that they award the money right then, but if you're successful you're invited to submit a proposal right?
Dr. Wachowiak: That's right.
Interviewer: Let's talk about the funding mechanism. This was a very, at least when I heard about it, it just seemed very unusual and like nothing I had ever heard before. What is an example of maybe the most surprising or oddest exercise you had to do?
Dr. Wachowiak: Well yeah, it was a very surprising mechanism you know. The idea was that we went to this workshop without any preconceived notions about what we would do as a project and we were actually given no agenda ahead of time in terms of what was going to happen at this workshop.
We didn't know who was going to be there in advance and of course we were supposed to, eventually, form groups with other investigators. So that was kind of interesting to go into the whole thing from the beginning.
I think the most interesting example of exercises was we had to very early on form our own little countries. We had to talk to everybody else and find people that we identified with in terms of how we approached science and how we define questions in the general field of olfaction.
So we had to meet other people, put ourselves in a certain sort of territory, give our country a name, give it a motto, define what our imports and exports are, things like that.
Interviewer: What was the name and motto of yours?
Dr. Wachowiak: Identestan or something. So we're interested in understanding how the nervous system encodes the identity of odors and what our exports were. What we produce for other people, we produce obviously information and data that other people can test with models. Our imports are techniques that we get from other people who are developing those things and hypotheses.
In other words, basically kind of a scientific speed dating exercise. You spend two minutes with a person, find out what they work on, try to identify a project that the two of you can work on together and describe what that would be within a couple of minutes.
Interviewer: What do you think the purpose is of those types of projects were?
Dr. Wachowiak: A lot of these exercises, and that was just one. We did many different kinds of exercises. But I think a lot of them were aimed at breaking down barriers to communication. Getting people out of their comfort zone and broadening the way they think about science. I mean, as scientists, we tend to spend a lot of energy focusing on problems in a fairly narrow way and you have to have something to disrupt that way of thinking.
So a lot of it was aimed at that, getting people to think big without doubting whether they might be able to approach these problems. Also just learn about what expertise other people have to bring to the table.
Interviewer: At the end of the workshop, what was the end product?
Dr. Wachowiak: The end product of the workshop itself was really a 12 minute talk. We were all joking while we were there, I mean this was really like a reality TV show.
Interviewer: Because all the program officers were watching you do this whole thing too, right? Probably taking notes.
Dr. Wachowiak: Oh yeah, right. So there were program officers and there was a panel, a review panel of scientists who were brought in really to review those preliminary proposals. One thing that was interesting about that is they also served as mentors throughout the week.
A lot of that week was devoted to forming groups, generating ideas and so not really developing specific proposals and that phase of developing a specific proposal with a specific group of people really just lasted probably 48 hours.
Interviewer: Something that usually takes months right?
Dr. Wachowiak: And about 40 hours of that time, everyone was awake and working hard, so it was quite intense.
Interviewer: What did you think about all this? What's your lasting impression?
Dr. Wachowiak: When you're developing a big project in a very, very short time, you can always look back and think, "Well maybe if we had more time or had the chance to bring in more people into this project, it could have been even more successful."
So I think in that sense, it's still probably an experiment. It was definitely I would say kind of the most intense professional experience I've had in my career and so that was really just personally, it was a great experience to go through that and see what comes out at the end.
It's a great mechanism to generate ideas and to get people potentially working together that might not otherwise and I think that sort of process can work in a lot of different contexts. I think it's great, for example, for developing ideas internally in a context let's say of a retreat or something like that within an institution. It can work in a lot of different ways and so that was really one of the things that I took away from that.
Announcer: Interesting, informative and all in the name of better health. This is The Scope Health Sciences Radio.
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