eLife Episode 8: Rats won't rat on rats

31 January 2014
Presented by Chris Smith.

In this episode of the eLife podcast we discuss ants, rats, sharks and rays, and the pathogen that causes corn smut in maize.

In this episode

00:41 - Lost at sea

Over half of all shark and ray species are “threatened or near threatened” according to new estimates

Lost at sea
with Nick Dulvy, Simon Fraser University

Over half of all shark and ray species are "threatened or near threatened" according to new estimates, with species most affected being those that are large and live in shallow water, easily accessed by fisheries. The state of the world's Threatened sharks and raysoceans and what lies beneath the surface is relatively unknown, as Nick Dulvy reveals...

Nick - For the last fifty years, our activities and our quest for food have eroded a lot of the biodiversity on the face of the planet. And growing up throughout this, I often wondered what was happening underneath the water's surface. And indeed for 20 years now, we've become increasingly concerned about how much we're taking from the oceans. Catches are rarely recorded. Even when they are recorded, they're not recorded in sufficient detail for us to know how much of each species is being taken. The next problem is, we might have some insight in to what is being taken from the ocean. The challenge is to figure out what's left in the ocean and are those populations viable.

Chris - So how in this study have you sought to try to understand what the real picture is?

Nick - Well, IUCN, the International Union for Conservation of Nature, has developed a way of effectively crowdsourcing science. And individual PhD students and fishery scientists around the world may have a good detailed understanding of their particular part of the coast or the ocean. And what IUCN specialises in is bringing all of those people together so we can bring all of their individual jig-saw pieces together to make sense of them on the global scale and this is particularly important for sharks and rays. It's very hard for any one scientist to tell us about the status of any one species and it's because many of these species are not just found in the waters of one country or one region, so our main methodology is really bringing people together and bringing their data sets together. And we did this over a period of 18 years. We had 17 workshops around the world that were attended by 302 experts and scientists.

Chris - So out of this big metro analysis, what trends have emerged and are the results in line with the worrying signs that we were picking up from the incidental reports that have been filtering through over recent years?

Nick - What we have estimated is that one-quarter of the world's sharks, and rays, and chimaeras are threatened with an elevated risk of extinction and we also find that a relatively small proportion are actually safe, so less than a third and closer to a quarter, on the Red List are the least concerns. So this is a group of species that has got a very high proportion that are threatened and a very low proportion that are actually safe.

Chris - That's a terribly high number, isn't it?

Nick - Indeed. The only animal groups that are more threatened than the sharks and rays are the amphibians.  About a third of amphibians are threatened and the stony corals that make up our coral reefs.

Chris - Now those are the animals that we are studying. What about the ones we are not?

Nick - Indeed. One of the most alarming findings for us as a scientific community was that around 487 species or half of the total were classified as data deficient. That means we did not have enough information with which to determine to the extinction risk status and of course that means that some fraction of that huge group of organisms are actually likely to be threatened.

Chris - People talk about a population point of no return. Once you diminish a population down to a threshold level where the genetic diversity means that there's no prospect really of recovery, for the 25% that are in that really threatened bracket, have we breached this population point of no return or is there still hope to rescue the situation?

Nick - What this study doesn't really tell us is when sharks will go extinct. Part of the reason for that is that we're concerned about the status of sharks because of their rate of decline and just like dropping a ball out of your hand, gravity inevitably takes it to the ground. And what's happening here is that unless we halt these declines, then the gravity of declining populations will inevitably lead to their extinction. We don't know when that will happen but we hope we will have enough time in which to implement management and conservation action.

Chris - What's it going to take?

Nick - Well, a large part of the problem is that fisheries managers and conservation biologists are just spread incredibly thin. They're very often not very well resourced. When I worked at the UK government Fisheries Agency, there was only myself and another colleague who had a side interest in sharks and we pursued that side interest, but we were never paid to work on that. But I think as these red listings highlight species of concern in particular places, then it motivates governments and government agencies to focus on these species and that's what our next job really is to do is to use these Red List assessments and the concerns raised by them to motivate more resources being put into conservation action and fisheries management.

06:15 - Why rats don’t rat on other rats

A rat will help another rat if it is familiar with that type of rat, even if it has not met the actual rat before.

Why rats don’t rat on other rats
with Peggy Mason, University of Chicago

Friends help each other and that goes for rats too, surprisingly. In fact, rats that know each other will release one another from a simple Rats help other rats escapetube structure that can only be opened from the outside but what about rats that don't know each other and they're strangers, or rats that look totally different from each other because they're from a different strain for example? Peggy Mason from the University of Chicago helped to answer this...

Peggy - When we first saw that they opened for strangers, we were very surprised. And so what we wanted to do was then to test them with a different strain. So what we did was we decided to use the Long-Evans strain and Long-Evans strain is not an albino rat. It's this quite attractive rat that has a white coat background and then it has a black cape, and they're very attractive. We did two conditions. We did one where the white rat lived with the black caped rat, and one where the white rat had never seen a black caped rat before and was exposed to 12 different black caped strangers. When they were cage mates, the white rat opened for the black caped rat. No problem. When they were strangers, they did not open. It was really remarkable.

Chris - So just to crystalise that for a second. So you've got a situation where this rat can clearly recognise a different strain of rat and if it knows it, it lets it out. If it doesn't know it and has never seen that strain before, it's suspicious and doesn't let it out.

Peggy - That was our hunch but there was one other possibility which could be something more complicated, which is that if it's not your strain, then you have to know the individual. That would also explain the results. But along the way, this incredible serendipitous event occurred. What happened was that in the cage mates, the white rat that was living with the black caped rat, one of the black caped rats got a tumour in its liver and he died. So what we did was, with the surviving white rat, we housed him with another white rat and then we exposed him to the strangers. And this was just a one off. We weren't going to publish this, this was just to see what would happen. And what happened was this guy helped every stranger. He was a tremendous opener helper. And what that tells you is that all it takes is familiarity with the type of rat but not with the individual, that the individual rat does not matter whether it's your own strain or a different strain, it doesn't matter. The only thing that matters is that you have to have been exposed to that type of rat.

Chris - So I suppose one way to explore that then would be what would happen if you took a baby, let's call it a baby white rat and you put it into a family of caped rats which look totally different, so it's the odd one out, but it thinks that that mother is it's real mother. It'll grow up with litter mates that look grossly different to it. What happens then?

Peggy - And that's exactly the experiment we did. We wanted to know whether the white rat innately knew that it was a white rat and would therefore grow up to help other white rats. So we put that to the test. On the day they were born, we took the white rats and we put them into black caped litters. So they had a black caped mom and black caped litter mates. And when they were adults, we tested half of them with black caped rats and as you may imagine, they helped the black caped rats. That's who they've lived with their entire lives. But the real question was, would they help the albino rats, which is what they are? But they've never seen another one. And the answer was, no, they did not. And that is really remarkable. It tells you that genetics does not inform a rat who they are and who they should help. What informs them is who they experience, who they interact with as they are growing up. 

Chris - What do you think the importance and implication of this is?

Peggy - I think that this is another one of the ways in which social cohesion is built. It's very important that animals that live in a group function well in a group. Groups hunt better, group protect themselves better, you're more likely to succeed and reproduce if you're in a cohesive group where you can gain, not only from your own actions but from other's actions as well. And we can even go a step further, and I will go a step further. Humans are mammals and I think that this not only tells us something about rats and other non-human animals but it also tells us about humans. Biology is part of empathy. Biology is part of how we react to others who are in distress and it's part of how we decide that we're going to help this individual in distress and then perhaps maybe not that individual in distress. It tells us that, as in the rats, a diverse environment is more likely to lead to extended helping of different types of individual.

Chris - So, it's official. Rats are racist. At least, until they make friends with each other. 

11:39 - HIV Complex problem solved

Researchers have worked out the structure of a protein complex that is involved in the destruction of T helper cells by HIV.

HIV Complex problem solved
with Jim Hurley, University of California, Berkeley

HIV nef interacts with AP2

Researchers have worked out the structure of a protein complex that is involved in the destruction of T helper cells by HIV. We spoke to Jim Hurley from the University of California...

Jim - One of the interesting aspects to this whole class of cellular hijacking events is that it creates a vulnerability for the virus. So HIV has three enzymes - the reverse transcriptase, the integrase, and the protease, and these three enzymes are the targets for all of the approved drugs that are currently used to control AIDS, and do so quite effectively. However, there is an issue that the virus mutates rapidly and eventually, acquires resistance to these. So, we always need other lines of attack. And the human proteins obviously aren't evolving rapidly. Only the viral proteins are mutating. So if we can find places on human proteins that are used by the virus, but that might not be important for ordinary cellular functions, those would make excellent targets that might not be subject to this sort of rapid drug resistance. Now because we know that this process of downregulation of CD4 by NEF is so important for infectivity, this seemed like one of the excellent places to start.

Chris - So how did you go into the cell and ask where the NEF protein is acting in order to bring down the CD4, to rob the cell surface of this important molecule?

Jim - This information was pieced together over about two decades by many laboratories. A key insight that led to the current study came from the lab of my colleague, Juan Bonifacino, at the NIH. And what he did was carry out a screen in the cells derived from the fruit fly, of all things. The fruit fly isn't normally infected by HIV, but he created a clever screen in order to deduce which cellular proteins were most important for downregulating CD4s and discovered that only a handful of proteins worked with NEF and were absolutely essential for the effect. These are called a clathrin, which is a vesicle coat protein, and AP-2. AP-2 is what's called an adaptor protein. So it links a cargo protein. A cargo protein is whatever it is that gets downregulated to clathrin, in order to create a coated vesicle, which will then internalise into the cell and eventually carry the substrate protein to its destruction. So, the highlight of that work was the discovery that AP-2, of all the potential adaptors involved was the key factor in linking NEF and CD4 to each other.

Chris - And is that the one that you went ahead to look at?

Jim - Right. So in the current study, we characterised the interaction biochemically. So we able to measure the affinity, but more importantly, we were able to obtain crystals of the complex of the part of AP-2 that binds with NEF and obtain an atomic structure. So now, we can see atom by atom, the details of this interaction with great precision.

Chris - Does this reveal the long sought after, sort of virus-specific interaction that might be a target for a drug to interrupt that process?

Jim - We're quite excited about it because NEF has a motif - a region within it that copies the interaction's normal cargo use - and now when we perturb those new interactions, we can cripple the ability of NEF to downregulate CD4 in model cells. So, the site looks quite promising.

Chris Smith - What about the big R? The resistance problem. Because if you put pressure on the virus by interrupting that motif, that interaction, how easy will it be for the virus to mutate to surmount that problem?

Jim - It's certainly a possibility. So, I don't think we can rule out that that the virus will find a way around it. What the virus won't be able to do is to mutate the AP-2 side of the interaction. So, we'll have to find a different surface on AP-2 to interact with.

16:54 - Into the maize

The pathogen that causes corn smut in maize employs a sophisticated strategy to increase its virulence.

Into the maize
with Regine Kahmann, Max Planck Institute, Marburg

The pathogen that causes corn smut in maize employs a sophisticated strategy to increase its virulence. Regina Kahmann, from the Max Plank Institute in Marburg, Germany has solved a mystery in maize, 

Corn Smut Disease in Maizewhich is vulnerable to infection by fungus called, Ustilago maydis. It triggers tumours to form in the plants, and bizarrely, it makes them produce the deep red pigment, anthocyanin and now, we know why.

Regine - The pathogen is very unusual. It infects maize, then the symptoms are huge tumours produced on all above-ground parts of the plant and it's in this tumour tissue that the fungus proliferates and produces spores. It's very severe. If you ever tried to grow sweet corn in your own garden, then it's very likely that you will get an infection.s tumours to form in the plants, and bizarrely, it makes them produce the deep red pigment, anthocyanin and now, we know why...

Chris - So how did you approach trying to study this pathogen to work out how it clearly does manage to bypass the defences in sweetcorn?

Regine - The idea here was to basically take the genes for all these unknown proteins that are predicted to be secreted and delete them. That is very easy in this system. And then ask, can this modified fungus still infect? And if the answer is yes, but not so well anymore, the question is to find out where it is arrested, how far does it get, and why does it not get any further? And why does it not get any further is then accompanied by trying to find out which plant protein does this fungus protein interact with.

Chris - You make it sound very simple. I suspect that this was molecular clockwork that took quite a lot of unpicking. What did you find when you began to delve into this?

Regine - Well here, it was relatively easy because it turned out that when we identified plant proteins interacting with this fungal protein, there was only one. And this was an enzyme, it was an enzyme that modifies other plant proteins of kinase. The amazing thing is that the fungus targets a specific region, of this kinase which normally serves for the degradation machinery to degrade this protein. And by this fungal protein, the kinase is stabilised and then it becomes active.

Chris - So what effect does bolting that kinase into the on position actually have on the plant cells?

Regine - Okay, so what we think is happening is that this stabilised kinase actually alters the activity of a regulatory protein and this regulatory protein will then stimulate the expression of about 8 genes, all involved in the biosynthesis of a red pigment which is called, anthocyanin.

Chris - This is the same stuff that makes beetroot go deep red, isn't it? Sort of an antioxidant molecule, isn't it?

Regine - Exactly.

Chris - So what is it doing that for then? Why would it want the plant to make heaps of anthocyanin?

Regine - Yeah, this was really the most intriguing question and the one that kept us busy for a very, very long time. If you want to make this anthocyanin, this red colour, you need precursors and interestingly, one of these precursor molecules is also a precursor for lignification for lignin biosynthesis. So, lignin is a very complex structure that is made by many plants to stabilise the cell wall.

Chris - It's woody stuff.  I mean, to put a sort of simple word on it, it's wood isn't it?

Regine - Yeah, it's wood.

Chris - So let me guess then, where you're going to go with this. You're going to tell me that by depriving the lignification process of raw materials, because they're all being bypassed into making loads of anthocyanin, this is going to stop the plant from laying down wood which would normally block up various tubes and passages and sequester the fungus in one part of the plant, stop it spreading.

Regine - Exactly.

Chris - Wow! I got it right. I'll go to the top of the class. Is that what we think is going on?

Regine - Yeah, this is exactly what we think is going on and you can actually show two things. One is, specific ways to visualise the lignin and interestingly, when you make this red pigment, there is very little lignin you can see. And this also means that the fungus gets to a certain compartment, in this case the veins, where the plant transports nutrients, and it actually gets inside the veins and we believe that this allows the fungus to get nutrients. And if you don't have this protein, this effector, then this region is heavily lignified. And you don't find the fungus inside this tissue anymore, and we think it's starving basically.

22:21 - Evolution at work in ants

The body shapes of queen ants and worker ants have evolved in different ways to reflect their different roles.

Evolution at work in ants
with Roberto Keller, Gulbenkian Institute, Portugal

The body shapes of queen ants and worker ants have evolved in different ways to reflect their different roles. A careful dissection of their necks can tell us about how Ant queentheir queens behave. Roberto Keller from the Gulbenkian Institute in Portugal told us more...

Roberto - These insects are very strong. They're able to carry things around that are much bigger and heavier than them - 30 times their own weight. So, what is it in their anatomy that allows them to do this? Of course, the other question was, well if you have a system where you are producing queens and workers, and each of them are doing different behaviours within the colony, how is it that their anatomy is optimised to the task that they are going to be doing?

Chris - So tell us a bit about the experimental method. What did you do to try to explore this question?

Roberto - So, it was two parts. We wanted to describe what are the differences in the anatomy between the queens and the workers? And for that, we looked for different species. We collected in the field, we also went to museums, and we'll basically do dissections and take photographs of the different muscles, and tried to see which muscle corresponds to which one in the worker and the queen and see how are they different. We wanted to quantify the differences. So we went and measured the different thickness in the thorax of queens and workers of many different species. Once we established that there is a pattern of differences, we wanted know if these differences is something that all ants have. So, we carefully chose species that will represent all the different groups of ants that are known, and try to see if the differences we first established were present in all the species.

Chris - What were the differences that you saw?

Roberto - One the one hand, the fact that the segments in the thorax of the queen will match their behaviour, meaning the first is not very large because they are not lifting things around. The second segment is very large because they are flying away, and they have all these wing muscles. And in workers, the first segment is always very enlarged because they will be using their head as a crane to carry things around and so they need these very, very strong neck and shoulders. Whereas, they all have a very reduced second segment. While we start doing the survey, we find out other things that we were not expecting. And that's that queens in ants across species are not all the same. The first segment, the one that has the neck muscles, in some queens is very, very reduced. The second queen's first segment was enlarged, it was never as big as a worker's, but it was certainly much more than in the other type of queens.

Chris - Is it something in the behaviour of those queens that would be a reason for that?

Roberto - By the time I was doing this work, I have a collaboration already established with Christian Peeters, and he specialises in ant behaviour. So one day when I start showing these patterns of the different queens, he suddenly jumped and realised that it appears that the difference of the anatomy of the queen was a reflection also of a certain difference we already knew that existed in the behaviour of the queen. And the majority of the queens you will see around, when they are virgin, they will fly away from the nest, mate with a male, then go to the ground, shed their wings, and burrow themselves, and start a new colony by themselves. Now what the queen does is that it never leaves this nest to look for food, what it does is it metabolises it's huge wing muscles that she will no longer use and she will use that to feed the first generation of workers. Now, the other type of behaviour that is more primitive is that the queens do something similar but then they will go out and hunt and look for pieces of food to feed the first generation of workers.

Chris - So, can I speculate then that the ones that do this more primitive hunting behaviour, don't have this enhanced musculature that they're then going to use to feed the colony. So they have a smaller section compared with the ones that do feed that colony off their own muscles.

Roberto - Yeah. That's exactly the case. They won't have to go and hunt. They have a slightly bigger first segment that will help them hunt and carry things around, but because they will not metabolise their wing muscles, their second segment is not very large. Where the ones that do metabolise the wing muscles have a huge second segment with huge wing muscles that are not only used for flight but of course they are proteins that can be used for function in the colony.

Chris - So, by studying the neck structure of the queen, you can work out whether she is one of the hunting type species or a non-hunting type which can spare you the need to do sometimes very laborious field studies.

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