Prof Ray Goldstein - Cambridge University
Now it’s time to hear more from the Genetics Society Autumn Meeting, from Genes to Shape. Professor Ray Goldstein, from the University of Cambridge, studies how molecules organise themselves inside cells, focusing in particular on plant-like algae called Chara. I asked him to describe to me what you can see inside the surprisingly large cells of these plants if you look down a microscope.
Ray - You'd see a beautiful stately flow of about up to a tenth of a millimetre per second. Sounds ridiculously slow, but by biological standards, that's fast. In a kind of barber pole arrangement, two helical bands of flow, one going up the cell, one going down the cell in this beautiful regular pattern. You'd see various organelles within the cell being carried along by this streaming. It’s driven by the action of motor proteins that walk along filaments. So for instance, myosin walking along actin or kinesin walking along microtubules, and carrying cargo one store to another, the action of moving that cargo entrains fluid. And because there's some kind of long range order in the filaments, one sees ordered pattern of one degree or another in the fluid flow.
Kat - So, we’re not talking about just fluids sloshing about inside a big cell. This is a very, very organised system.
Ray - Well, there are two basic types. There are those that are super highly organised, regular geometric structures and there are others that are more disordered such as in the oocyte of a fruit fly which is one commonly studied situation. But even there, it’s not completely disordered. The microtubules that drive it are organised from the cell periphery and although it looks a bit turbulent or chaotic to the eye, there is structure in it anyway. So, it is a structured flow to some degree enough.
Kat - So, what's the question that your work is trying to answer?
Ray - Our work on cytoplasmic streaming is fundamentally aimed in understanding its role in biology. There's been a lot of work over the centuries in visualising it and quantifying it, but there's still not a clear indication of its purpose. Is it to mix the contents of the cell, is it a by-product of a transport process? It’s very unclear. So, we’re trying to unravel this step by step.
Kat - So, you can almost imagine this little army of proteins marching things around the cell. How do you study them and how do you tell what they're up to?
Ray - Well, the first thing is, one can visualise the flow, independent of the driving force, by having tracer particles of one sense or another. So, they give you a direct readout of what the fluid flow is doing. But it’s also possible to label the various agents going on here and actually to have a direct visualisation in one sense or another of the cargo.
Kat - The fascinating thing about these kind of systems – the flows and all these things – is that they are completely directed within the cell by itself. They're self-organising. What are the clues that we have so far about how these work?
Ray - Well, I would say that in the case of large plant cells, which is the one that I've been focusing on most, there are tantalising experimental observations that show that you can disrupt the underlying network of the filaments. When these chemicals that do get disruption are removed, the system can heal itself and reform the pattern of streaming, perhaps with a different precise origin and all of that, but it’s the same basic pattern just shifted around a bit. That already speaks to self-organisation.
We also know that as some of these cells grow, the pattern changes in a systematic way and this suggests that there's a very clear direction going on, but again, this further indicates a self-organisation process. In the case of the more disordered flows, we have changes that occur during development that really speak to self-organisation processes, some chemical that was present in large quantities at this point in time disappears and then all of a sudden, a new pattern emerges.
Kat - And how widely across biology do we see these properties of self-organisation at this kind of level happening?
Ray - Well, without being too clichéd, I think that it’s fair to say that self organisation occurs on length scales ranging from a few microns to a few kilometres. You can look at wildebeast on the plains of the Serengeti and you can see self-organisation into coherent locomotion. You can see that in locust swarms, you can see it in bacteria in a Petri dish and you can see it inside a single cell. Now, it’s wrong to just imagine that there's some single underlying mechanism crossing all those length scales, but the mathematical structure of a theory that would explain it can have some commonality.
Kat - And how close are we to coming up with these kind of theories or is it just very complicated?
Ray - I think we’re actually fairly close because certain model systems allow us to make measurements to test in detail the predictions of a theory. And so, we can apply what's known as the scientific method. Here we are in Royal Society where Newton was so prominent and it’s thanks to him we really use the scientific method. We can use that and go back and forth. We can do an experiment in a way that was not possible 10 or 15 years ago thanks to technological advances of imaging and microscopy.
Kat - Some of the work that we’ve heard about today, it’s looking at very specialised model systems, very rarefied things, or single cells. Do you think one day we will be able to describe the organisation for example of an embryo, a human embryo as it goes from one cell to many and all the things that move around there?
Ray - I certainly think we all believe so. We tend to be very reductionist so we start with simpler things where we think we’d have more capacity to understand all that's going on. But it’s remarkable how much progress has been made. Mostly, it’s a question of courage I think. We just have to sort of launch down the path and try to figure out what it is we need to measure and what a mathematical model would look like and how to test it and go back and forth.
Kat - For you, what are the questions that you still really want to answer? What are the known unknowns for you?
Ray - A known unknown would be basically the question of the purpose of streaming. Of course, it may not have a single purpose, but basically, why have cells engineered these large scale flows? Are the flows themselves just by-products of a transport process or do they play a particular role in the self-organisation that happens? This is often the case, it appears to be in the development of the body plan of higher organisms. We'd really like to have a connection between the microscopic action of the motor proteins that go whizzing along these filaments and the flows that we see. It’s not a very straightforward connection because fluid mechanics is complicated and the micro scales are hard to see. But those are the burning questions.
Kat - That was Professor Ray Goldstein from Cambridge University.