Come together

Now let's hear more from one of the other talks Buzz mentioned, from Professor Andreas Bausch from the Technical University of Munich in Germany. He's trying to understand how patterns and structures form in nature, and showed some beautiful and striking movies of simple molecules coming together to create all kinds of shapes that move around. I asked him to explain how he and his team generated these stunning images from simple biological molecules.

Andreas - So, my model system is the cytoskeleton which is a polymer network inside of cells. We try to purify the components and then we see how they self-organise in beautiful spherical spirals or going to form waves, and so on. We try to really control what kind of patterns emerge.

Kat - Can you tell me a little bit more about the cytoskeleton? What is it inside cells?

Andreas - So, this is a polymer network which makes the cells stiff and gives us all the shapes.

Kat - It's almost like a scaffold inside the cell?

Andreas - Yeah, right. It's a scaffold and it's responsible for all kind of processes of cell division, cell migration, transport inside of cells. So, it's a rather universal polymer network and there's a lot of physics behind it. I think the beauty here is that a lot of physical concepts and measurement techniques are necessary to explore this kind of very complicated polymer network. It's much more complicated than all the polymer networks we know from a daily basis. So rubber is trivial compared to the complexity we have in cells. That's actually what is life about. It's already have high complexity and high integration density of functionality on this very small scale to have all these functions on this very small length scales.

Kat - So, what do you do in your lab to study these very, very complex systems?

Andreas - The idea is that we go from a bottom-up approach where we purify components and add step by step complexity and control the complexity which is kind of completely different than traditional biology would do it, that they come from a cell organism and go down. We try to really be on the physics approach where we really add the complexity step by step.

Kat - So, you're starting with the building blocks of a scaffold, putting them all in a test tube and seeing what happens.

Andreas - Yeah. Basically, that's what we do. We mix and watch.

Kat - We saw some beautiful, beautiful things. Tell me about some of the patterns you see.

Andreas - So, we see spirals, for example, where they move around or the galaxy forms where you get density waves in the spiral. You'll see waves like ocean waves walking over the cover slide. The amazing thing is that we span a lot of the length scale. So, the single filament is 7 nanometre and patterns are up to centimetres. So, this is unheard of length scales you're expanding here, where you get really kind of higher order structures out of very small interactions at very small length scales. Then we see also some shapes where we have spherical objects which change their shape into citrons or scallops or whatever. So, there's all kind of a zoo of different patterns and forms which we have here. That's the fascinating shapes are the fascinating thing here.

Kat - Sometimes it can be hard to think how do we go from the information amount of genes, it makes proteins and then it organises into these amazing structures. But looking at your images, you kind of start to see how life might work.

Andreas - Yeah, I guess we're on the upper end from the gene expression. We don't think about gene expression and the regulation of the gene expression. We have already the proteins. If you just let 2 or 3 proteins interact, it starts to emerge, the shapes emerge and patterns and dynamics emerge, and that's the fascinating thing here. The goal is evidently that we really want to mimic some real process like cell division or cell migration in the test tube with purified components. That's the ultimate goal we have here.

Kat - What's the weirdest thing you've seen in the results that you've got?

Andreas - The weirdest thing, I guess they all were weird the first time we saw them because they all were unexpected. The most fascinating I think these days is now, these vesicles which change shape in a very deterministic way which we never expected, in a very kind of mathematically pure, which nobody would expect it because it should unordered. So, we see kind of pure physics and pure mathematics coming out from a very complicated four-component system and that's kind of fascinating.

Kat - Some people say, biology, it's really just applied physics. Do you think we can break down the amazing process of life to physical rules one day?

Andreas - I guess that's exactly what's happening right now and I think we need much more physics coming into this complexity of biology to really break it down to principles and identify principles behind it. I think these experiments showed examples where you see that there is some hope that we can come up with some minimalistic systems where you see that already 3 or 4 components do a function. In nature, in real biology, you may have 10 or 20 proteins doing that, but four with defined function are enough to do it. And then you would have understood quite a bit already.

Kat - That was Professor Andreas Bausch from the Technical University of Munich. 

Swiss scientists have made a step forward in understanding how resistance to HIV could be encoded within our own genes, according to a new paper in the journal eLife. Every person infected with HIV mounts some kind of immune response to the virus, and some people can even hold the infection at bay without taking anti-viral drugs. The researchers, led by Jacques Fellay, traced how HIV viruses sampled from more than a thousand infected people had genetically changed over time, in response to attacks by the immune system, looking at more than 3,000 mutations. 

Then they also mapped the gene variations in the human genome that might be responsible for fighting back. Importantly, the researchers needed to look at data from samples taken before there were effective HIV treatments, to make sure they were only focusing on the natural effects of the immune system, so they had to trawl databases from the 1980s. It's the biggest global overview to date of the genes involved in HIV resistance, and the scientists think that their results could one day lead to more effective, genetically personalised therapies.

If you've ever had athlete's foot, you've had a fungal infection. Such infections are common and easily cleared up with over-the-counter anti-fungal drugs. But in rare cases, such usually harmless fungal infections can get beneath the skin and spread to the bones, gut, immune system and even the brain, causing a condition called deep dermatophytosis which can be fatal. 

Writing in the New England Journal of Medicine, scientists at The Rockefeller University in the US and Necker Medical School in Paris have now discovered a gene fault that allows the fungus to spread in this way. To find the faulty gene, called CARD9, the researchers looked at DNA from 17 people who had succumbed to deep dermatophytosis but were otherwise healthy, with normal functioning immune systems. Previous research had suggested CARD9 might be the suspect, and the scientists found it was faulty in all 17 of the patients.

The scientists think their finding explains why fungal infections sometimes spread into the body, and why they can be so hard to treat when they do. In the case of families that carry the gene fault, this could lead to genetic testing, as well as prevention advice and targeted treatments. And it also lends weight to the idea that genetic variations between people make the difference between some people being able to shrug off minor infections while others fall seriously ill. 

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.