Host: Benjamin Thompson
Welcome back to the Nature Podcast. This week, fly brains and fMRI…
Host: Shamini Bundell
And the latest stories from the Nature Briefing. I’m Shamini Bundell.
Host: Benjamin Thompson
And I’m Benjamin Thompson.
[Jingle]
Host: Benjamin Thompson
A lot of neuroscience research tries to understand how the cells in our brain process information, but being a brain cell is hard work, and it takes a lot of energy to keep a cell functioning smoothly. Now, a new study from Stanford University in the US looks at how energy and information processing are linked in single cells. Reporter Ali Jennings rang up paper author Tom Clandinin to find out more. Now, you may notice Tom’s audio quality change a little bit during the interview, and that’s because his parrot was being a bit noisy and he had to change rooms. Anyway, here’s Ali.
Interviewer: Ali Jennings
What am I going to see if I walk into the lab and you’re doing one of these experiments?
Interviewee: Tom Clandinin
What you are going to see is a massive microscope sitting on top of a fruit fly’s head. The fly is going to be hanging out there, and we are going to be measuring changes in neural activity as it stays there for a half hour or an hour.
Interviewer: Ali Jennings
So, in this paper, what was the problem that you were trying to solve?
Interviewee: Tom Clandinin
What we were trying to do was directly measure how individual neurons use energy, which is something that hadn’t actually measured in vivo before, inside intact brains, inside intact circuits, and we took advantage of a new sensor to allow us to measure ATP levels, kind of the core unit of energy in the cell, inside fly neurons.
Interviewer: Ali Jennings
So, you’ve got this setup where you can see the amount of energy that individual neurons are using. What do you do then?
Interviewee: Tom Clandinin
What we are doing is controlling exactly when and exactly how much a particular set of neurons are active. This experiment gave us the most surprising result of the paper. Everyone was collectively sure that what should happen when you increase the activity of a neuron was that ATP levels should go down. Because the cell is more active, it’s consuming more energy, so ATP would fall. And what we found instead is that the cell is much smarter than that. It may have a very brief moment in time where ATP falls, but it immediately responds by kind of increasing energy production and ATP levels, and so the idea is what the cell is doing is guessing how much energy will it need in the future so that it can increase its energy production right now to anticipate that future need.
Interviewer: Ali Jennings
So, what does the work tell us about the brain itself, about the way the brain functions?
Interviewee: Tom Clandinin
I think what it tells us is that we need to think much more broadly about how the brain computes. Our brains are not computers. They’re not things you just switch on and off. They’re implemented by cells, and how cells couple their biology to changes in activity is really a big set of questions there that we know very little about, but which I think are really fundamental to understanding how brain function both is maintained when we are healthy and declines when we are not.
Interviewer: Ali Jennings
When I read the paper, a lot of it, the sort of rationale for doing it, appears to be couched around MRI. Now, that’s a brain imaging technique that measures blood flow. Blood carries oxygen and nutrients that neurons need to generate ATP and ultimately to fire. So if you scan someone’s brain and you see an increase in blood flow, you can infer that their neural activity has also increased. So, how is your work related to brain imaging?
Interviewee: Tom Clandinin
The way we thought about it when we started was, maybe at a more basic level, what’s the relationship between how the brain computes and the energy it uses to do so, but of course that’s relevant to human brain imaging because human brain imaging relies on measuring changes in essentially energy consumption.
Interviewer: Ali Jennings
What does the result mean for brain imaging?
Interviewee: Tom Clandinin
What we think it means for brain imaging is it sets a limit on how rapidly one could hope to measure changes in neural activity. The reason for that is when the cell makes its prediction about how much ATP it’s going to need in the future, it makes that prediction over many seconds, 50 seconds. In the context of neural computation, 50 seconds is an eternity, which will make invisible the shorter term changes in neural activity that one would like to measure using fMRI.
Interviewer: Ali Jennings
So, does that mean that when you look at an fMRI, what you’re seeing is actually what the brain thinks its activity is going to be rather than necessarily what the activity actually is?
Interviewee: Tom Clandinin
That is exactly right. So, what we think is that those signals are really predictions about the future needs of that area.
Interviewer: Ali Jennings
Does it suggest new possibilities for brain imaging technology?
Interviewee: Tom Clandinin
Absolutely. I mean, I think once you know kind of what the true kind of timescale of changes are, I think you can optimise how you acquire those signals. Now, I have to say, I’m the opposite of an expert in fMRI. I study the fruit-fly brain. But I think when this paper comes out I really hope that it does help think about both how you design fMRI-type experiments and how future developments of fMRI instruments might be optimised to take advantage of these signals.
Interviewer: Ali Jennings
So, you mention that this is a fruit-fly brain. MRI – we’d think about human brains. How transferable is it?
Interviewee: Tom Clandinin
Yeah, what we think is the way neurons couple their change in activity to their needs for energy is an evolutionary ancient thing that certainly predates the split between fruit flies and humans, and so that’s a space where I think flies and the very powerful tools we have available in flies really put us in a strong position to make measurements that are of value to a broad community.
Host: Benjamin Thompson
That was Tom Clandinin speaking with Ali Jennings. Head over to the show notes where you can find a link to Tom’s paper.
Host: Shamini Bundell
Coming up, we’ll be talking about the latest results from a malaria vaccine trial and the scientists digging up bottles of seeds in the dead of night, in the latest chapter of one of the world’s oldest experiments. That’s all coming up in the Briefing chat. Right now, though, it’s time for this week’s Research Highlights, read by Dan Fox.
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Dan Fox
A lobster’s underbelly is covered by a membrane that is strong but flexible, providing protection whilst still allowing the animal to manoeuvre. Now, that membrane has inspired a strong, flexible, synthetic material that could help pave the way for protective fabrics. The team behind this based their new material on a network of water-loving polymer chains known as a hydrogel, which they welded together with water and partially crystalised with heat, creating small, scattered crystals inside the fibres. Tearing the resulting film requires more than ten times the energy needed to rip up an uncrystallised sample, and further improvement came when the team stacked layers of polymer, with each layer at an angle to the one underneath it, just like the lobster’s soft armour. Read that research in full in Matter.
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Dan Fox
Global consumption of poultry and seafood, which are comparatively climate-friendly, has grown since the early 1960s, but that growth has not supressed people’s hunger for red meat. Beef and pork production releases large amounts of heat-trapping greenhouse gases compared to poultry and seafood. Now, new research into people’s dietary choices has found that while consumption of poultry and seafood increased between 1961 and 2013, consumption of beef and other meats has not fallen, despite growing evidence that eating less has benefits for both the climate and human health. The author of the paper cautions that patterns may have changed again since 2013, the last year for which data were available. But to seriously reduce greenhouse gas emissions, people would need to shift to a diet with a minimum of animal-based foodstuffs. Chew on that research in Nature Sustainability.
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Host: Benjamin Thompson
Now, before we get to the Briefing chat, a few bits of good news. The first one is that Coronapod, our spin-off show all about the pandemic, was awarded Best Coronavirus Podcast at the Publisher Podcast Awards last week, and a huge thanks to all the judges and organisers. And listeners, you can find all the previous episodes over at nature.com/podcast, and look out for the next episode later this week.
Host: Shamini Bundell
Secondly, as if that wasn’t enough, we’ve got an award nomination from the Webbys for our three-part mini-series ‘Stick to the Science’, which is all about what science’s relationship with politics actually is and what it should be. It’s a huge deal, so we’re super proud about that, but we do need your help on this one, listeners. So, aside from the main award, the series is also up for a People’s Voice Award, and there is actually going to be a link in the show notes where if you so choose you could spend a couple of minutes casting a vote for us and help us win that one.
Host: Benjamin Thompson
Yeah, that would be absolutely amazing. But now, let’s get back to this week’s show, and it is time for the Briefing Chat, where we talk about a couple of articles that have stood out to us in the Nature Briefing. Shamini, what have you got for us this week?
Host: Shamini Bundell
Yeah, so, big news this week. The Nature Briefing highlighted a BBC article, and Nature has also covered it, it’s a new vaccine against malaria, and one that’s been really promising in early trials.
Host: Benjamin Thompson
Right, I mean, we talk about vaccines a lot at the moment, with obvious reasons for the coronavirus and all that’s going on in the world, but malaria is, I mean, a huge killer around the world. It’s sort of staggering statistics. From what I understand, researchers have been trying to develop a vaccine for malaria for a really, really long time.
Host: Shamini Bundell
Yeah, there has been a lot of work into trying to develop vaccines, with good reason, as you say. Like the death rate for malaria in 2019, for example, was 409,000 people. But unfortunately, coming up with a malaria vaccine has actually been very tricky, and part of that is because of the complexity of the malaria parasite and of its life cycle.
Host: Benjamin Thompson
Let’s talk about this vaccine then. Who has made this one and what have they been testing?
Host: Shamini Bundell
So, this has actually come out from the team at Oxford who have also been working on one of the coronavirus vaccines. And the big problem with all the vaccines that people have worked on is the efficacy has always been low, of the things that they’ve tried so far, and the World Health Organization had sort of set a target and said, in order to be really useful, we need something that has 75% efficacy. So, this new vaccine – it’s called R21 – has had a trial in Burkina Faso in 450 children, and this first set of results suggests that this vaccine is up to 77% effective at preventing malaria. Now, that’s just the first trial. That could change because they’re obviously now going to go into a bigger trial with more children, but this could be the first time that we’ve been that 75% target.
Host: Benjamin Thompson
Well, I mean, that is fantastic news, Shamini, but of course, you’re right – it’s fantastic news tempered by it’s not ready for prime time just yet.
Host: Shamini Bundell
But it also doesn’t mean that other vaccine development programmes are going to stop. So, this particular vaccine is targeting a particular initial stage of the parasite life cycle, when it sort of first gets injected into the blood, and it also is boosting the immune system in order to try and wipe it out at that stage before any of those little parasites can get to the liver and get to the blood and start reproducing. But other vaccines are still in development which target different stages or kind of try and target all of them or potentially use a sort of attenuated version of a whole parasite to try and cover all the bases. So, those are also still possibilities, but malaria is still such a big killer that this is really important progress and a really important area in which to keep working.
Host: Benjamin Thompson
Yeah, absolutely. I mean, I think we’ll all keep our fingers crossed and hope for positive results from the next stages of this trial.
Host: Shamini Bundell
Yeah, so, what story have you got for us this week, Ben?
Host: Benjamin Thompson
Well, Shamini, this is a fascinating story that I read in The New York Times, and it’s about a group of plant scientists who, earlier this month, on the campus of Michigan State University, some hours before sunrise, followed a map and dug up some buried treasure. It really is quite something.
Host: Shamini Bundell
Is this really a highly secret scientific endeavour or was there some reason that they had to sort of do it all before sunrise with a secret map?
Host: Benjamin Thompson
Yes to both, actually, Shamini. So, what they were digging up was a bottle filled with sand and some really, really, really old seeds that had been put there back in I think it was the late 1800s by a botanist called William James Beal, and every 20 years, scientists come and follow this map and dig up one of these bottles and they then see if they can get some of these plants to germinate, and apparently it’s one of the world’s oldest running experiments.
Host: Shamini Bundell
Oh, so the idea is do they still germinate even though they’ve been buried in sand for 100 years?
Host: Benjamin Thompson
Basically, that’s what it was at the start when William James Beal set this up, and he wanted to know how long seeds would last in the soil and what it took to kind of germinate them, maybe to help farmers kind of get rid of weeds in their seed stocks. But obviously, this has been going on for quite a long time now. So, he buried a bunch of these bottles with the idea that every five years one of them would be dug up to see what was going on, and there’s like over 1,000 seeds, like 21 different species. And the time has been expanded between them now, and it’s every 20 years, and this experiment has been running for 142 years at the moment, and researchers reckon that maybe there’s 80 years left to go.
Host: Shamini Bundell
So, they have enough seeds to keep going, but I mean, are the seeds growing, like does it work? Can you bury a seed for that long and have it still germinate?
Host: Benjamin Thompson
Well, yes, great question, and over the years, the number of seeds that have germinated has dropped. Apparently, there’s only one sort of reliable sprouter left, as they describe it in the article, and in 2000 that was – and I hope I’m pronouncing this right – Verbascum blattaria, which is a yellow flowered herb, and that will still sprout despite having been underground for over 100 years. But if that was maybe the setup at the start of this experiment, to see whether stuff geminated or not which is kind of a ‘yes’ or ‘no’ answer, obviously, plant science has developed immeasurably since 1876, and now researchers are able to kind of look inside some of these maybe non-germinating seeds and look at the DNA and the RNA and all the machinery there and work out maybe why seeds aren’t germinating, which is super interesting and maybe really useful for seed stocks and things like that to try and work out how you can make seeds viable long term.
Host: Shamini Bundell
This is fascinating, but I really don’t think any of this explains the sort of ‘sneaking around with treasure maps in the dead of night’ part? Why is this a secret?
Host: Benjamin Thompson
Well, I think partially it’s a secret to stop people getting super interested and wanting to go and have a look for themselves, given that it’s been going for so long. But what is beautiful about this is that the location of these bottles is kind of passed down from generation of plant scientist to generation of plant scientist, and they dig the bottles up at night, obviously, to stop any light getting to the seeds and maybe sort of messing up the germination pattern, and also apparently they wear green head lamps as well to avoid that too.
Host: Shamini Bundell
Oh.
Host: Benjamin Thompson
Yeah, so it’s been running for absolutely ages now, and they’re going to do some interesting things as well with some of these seeds. They’re going to expose them to smoke and see if they can get some of these ungerminated seeds to revivify because obviously we know some plants do well after a forest fire, for example. They’re going to cool some down to give them kind of a second winter because sometimes that can get plants to germinate. But yeah, it’s amazing, and I think what also blew my mind, Shamini, is the next time this happens is going to be in another two decades when another group of scientists goes out with this map and tries to work out where they are on the campus and find another one of these bottles.
Host: Shamini Bundell
That’s so cool. I love it.
Host: Benjamin Thompson
Yeah, absolutely. Well, Shamini, let’s leave it there and listeners, we’ll put links to those two stories in this week’s show notes so you can read a bit more about them both, and if you’d like other stories like this delivered directly to your inbox, you should sign up for the Nature Briefing, and we’ll put a link on where you can do that there as well.
Host: Shamini Bundell
Well, that’s all for this edition of the Nature Podcast. Don’t forget, as always, you can reach out to us on Twitter – we’re @NaturePodcast. Or you can send us an email – we’re podcast@nature.com.
Host: Benjamin Thompson
And don’t forget to vote for ‘Stick to the Science’ in this year’s Webbys. Head over to the show notes once more for the link. Thank you so much. I’m Benjamin Thompson.
Host: Shamini Bundell
And I’m Shamini Bundell. Thanks for listening.
Malaria vaccine shows promise — now come tougher trials
