Neuronal sushi belt

14 February 2017

Interview with

Dr. Timothy O’Leary, University of Cambridge

The nerves or neurones that send messages from one end of the body to the other have fascinated anatomists for over a century. An outstanding question is how do these cells, which can be metres in length, keep all of the remote parts of the cell supplied with energy and raw materials, which are normally made in just one central region of the cell. One popular idea is that neurones contain the microscopic equivalent of a conveyor belt system which transports materials to where they need to go inside the cell. But, by building a mathematical model of how this happens, Chris Smith met one scientist who has found that anyone waiting for their dinner to be delivered by a system like this would end up very hungry indeed, so something else must be going on…

Timothy - I'm Dr Timothy O'Leary, based at the University of Cambridge, and I'm a lecturer in information engineering and neuroscience. Today we're in a sushi restaurant in Cambridge and it's one of those sushi restaurants that has a snazzy belt mechanism, that allows all of the dishes to be delivered to the customers as they sit around the sushi belt. 

Chris - What has this got to do with cell biology?

Timothy - The cells I’m interested in are neurons, and neurons are the cells that essentially make your brain work. A typical person has around 86 billion neurons and one neuron can, potentially, connect thousands of other neurons and it’s this connectivity that give your brain it’s power.

So, how do neurons connect to each other? Well, in order to reach out and connect to their neighbours they have these long, thin, branch like processes called dendrites. So if we looked at a neuron under a microscope, it would look like a tree, a very bushy tree with lots of branches and some of them very long. If we were to zoom into this neuron and look inside one of the branches, we’d see there are lots of things moving up and down the branch. And this is because neurons are composed of lots of proteins and small components that all need to be manufactured and moved around inside the cell.

So sometimes material needs to be made in one part of the cell and then shuttled along to another part of the cell. And the analogy that we use is the sushi belt because there really is something inside the cell that moves this cargo along in a similar fashion to a sushi-belt.

Chris - Effectively you can imagine the analogy is the nucleus is the recipe book with the chef standing there cooking stuff, putting it on the plates that then go on the sushi-belt, and they’re carted round the cell and the customers (the parts of the cell that need them) are going to be lifting dishes off the sushi-belt at various points and using them.

Timothy - That’s just the picture that we have, yes.

Chris - What’s wrong with it?

Timothy - Life isn’t really like that. At the molecular level the movements of these particles are stochastic, that means that there’s a chance element in it. To explain what that would mean in the sushi restaurant analogy, let's imagine that we’re waiting for a tuna roll and it’s a few feet away, but then randomly the belt changes direction and starts moving the other way. That would be very frustrating. But what would be even more frustrating is if the person next to us, who doesn’t even want the tuna roll, just took the tuna roll, sat it on their table for a while and then maybe decided to put it back on the belt. Those are the kinds of things that can occur at the molecular level by chance and it’s for this reason that we can expect long delays sometimes in this transport mechanism within a neuron.

Chris - Can cells tolerate not getting it’s tuna roll for ages or, actually, are you saying that this is such a significant constraint there must be something else going on because cells would not be able to put up with that?

Timothy - That was actually the motivation for this study. What we did was we took experimental data where scientists had measured the movements of these microscopic particles. Then we simply took the measurements and we did the math and we figured out how long it would take, on average, a collection of particles to move across a typical sized neuron and the number turned out to be disappointingly large. It can take many hours or days to distribute cargo throughout a typical neuron. And this came as a surprise because many of us thought that cargo could be distributed on the order of minutes or hours at the very worst.

Chris - Is is not that the cell does something else, which could be it says well I’ll tolerate some constraints of the sushi belt but, at the same time, I’ll also have my own local solution? So I’ll make some stuff myself locally so I’m not held up, so if it’s not available on the sushi belt right now, I’ll make my own?

Timothy - That’s absolutely true and, in fact, in recent years it’s been observed that neurons do have the capacity to make things that they need locally. However, the ingredients for the things that they make locally, and the machinery for making them, still need to be delivered to those sites and our claim is that that may take a lot longer is currently thought.

Chris - I suppose what you have done is to highlight some of these inconsistencies but you’ve also now generated with this model a bunch of testable hypotheses?

Timothy - That’s absolutely true. So it’s now becoming possible to peer inside a living neuron and watch these components moving around. And the kinds of experiments people can do now can start to address some of the predictions of the model. We might find that actually neurons are far cleverer than we think and they’re able to distribute components far more efficiently than our calculations suggest and that’s why our model made the minimal possible set of assumptions. Now, if further observations contradict those predictions, then we know that there are actually parts missing to our understanding of this molecular sushi belt.

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