Mosquito bloodlust hormones & inflammation drives long Covid

Plus, the Royal Society Summer Science Exhibition 2024
05 July 2024
Presented by Chris Smith
Production by Rhys James.

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In this edition of The Naked Scientists, Body scans give us new insights into long COVID; scientists discover the switch that triggers a mosquito’s blood lust; and we’ll take you on a whistle-stop tour of Royal Society’s summer science exhibition...

In this episode

COVID inflammation

Long Covid linked to persistent inflammation and viral RNA
Michael Peluso, University of California, San Francisco

Scientists in the United States have been scanning patients with long covid symptoms in a bid to assess the long-term impact of the SARS-CoV-2 virus. They’ve done it by using a special imaging technique which lights up when it sees inflammation. Michael Peluso is at the University of California, San Francisco…

Michael - The purpose of this study was really trying to understand what's going on with the immune system on a total body level after a person has Covid and whether that could be related to long Covid.

Chris - How?

Michael - So we know from studies of blood tests that people after they have Covid have sort of lingering inflammation and that people with long Covid may have more inflammation than other people. Their immune systems may be revved up for quite some time, but the blood is only a small window into what's going on in the totality of somebody's body. And so what we did in this study was try to understand what the immune system was doing in all of the various tissues, basically from head to toe in a person in the months or even years after they have Covid.

Chris - And how can you actually ask that question in a living person without taking them to pieces obviously <laugh>, how do you know what the activity of the immune system is on a tissue by tissue, organ by organ level?

Michael - So a few years ago before the pandemic, my colleagues at UCSF, Tim Henrich and Henry Vanbrocklin, actually developed this special PET scan with what we call a tracer. Basically a molecule that we inject into people's veins into their arm and it goes throughout their body and basically lights up tissues that have increased levels of immune system cells trafficking into them. People do this special scan and the areas of their body that are particularly active with certain types of immune cells called T cells light up on the scan compared to tissues where there aren't a lot of those types of cells. And so what we're basically able to do is look tissue by tissue region by region at the level of immune activity in each of these different places. So in the brain, in the lymph nodes, in the spinal cord, in the heart, in the lungs, in the liver, in the GI tract. And that gives us a sense of where that signal of inflammation that we might be seeing in blood is actually coming from. It has to be coming from somewhere. And so this was sort of a look into where it could be coming from

Chris - Just in people with Covid or a range of patients?

Michael - So the purpose of this study was to really understand what happens to people after they have Covid. And so the majority of the patients that we scanned were, you know, one month, two months, three months, six months a year, two years after Covid. And many of the participants had what we call long Covid symptoms that persist and are otherwise unexplained after a person has Covid. But something that was really important that we did in this study was because our program existed before the pandemic, we were able to use archive scans from before anybody on the planet had Covid to understand what was the normal level of immune activation, you know, five or 10 years ago. And what we found basically across the board was that in people who had had Covid their tissues lit up compared to what was typical before Covid existed.

Chris - Did you look at people who had and hadn't been vaccinated against Covid? Because could that also be playing a role?

Michael - We typically record when everybody in the study gets their vaccines and we did not actually scan people in proximity to getting a Covid vaccine. So the participants in the study had to be several months away from having gotten their most recent vaccine. And a number of participants in the study participated before vaccines even became available. So we don't think that the findings are in any way attributable to vaccination.

Chris - And what did they reveal when you scan these people over time in relation to Covid infection? What does that reveal?

Michael - Regardless of whether people were two months after Covid, six months after Covid, a year after Covid, there were signs of increased inflammation and increased immune system activity in a number of different tissue sites from the lungs to the heart to the GI tract compared to people who had never had Covid.

Chris - Can you point the finger though, at what's driving that sustained inflammation over time? Is that physical virus still there? Because one of the theories of long Covid is that people have some kind of reservoir of long-term infection that continues to tickle the immune system all over the place. Others have said it's almost as though the immune system just gets locked on like autopilot. So which do you think it is?

Michael - Yeah, so both of those things are certainly possible. And when we went into this, our framework for this was that the virus should come and go and we shouldn't be able to find anything beyond the first couple of weeks after a person has had Covid. So one of the really interesting things we were able to do in this study was, you know, we saw all of the various tissues that lit up that had increased immune activity. And you know, you can't do brain biopsies on living people and heart biopsies. The risk is just too high. But one of the areas, as I mentioned, that lit up was the GI tract. And so we were able to basically in a subset of these volunteers do a procedure called a flexible sigmoidoscopy where a gastroenterologist goes in with a camera and takes a little biopsies of the rectal wall basically. And what we found in basically everybody who was biopsied, all these people had long Covid, was SARS-CoV-2 RNA that should not be there. And so that suggests to us that in at least one of these areas of inflammation that we're seeing, the GI tract there is a relationship between that inflammation and pieces of this virus that are sticking around.

MOSQUITO

Mosquito bloodlust controlled by two hormones
Michael Strand, University of Georgia

Mosquitoes cause more disease and deaths than any other creature on the planet, because they are the vector for a host of horrible diseases. But now a new study has found that a pair of hormones work together to either drive or deactivate a mosquito’s blood lust. So maybe we can exploit them to stop ourselves being bitten. To explain more is the paper's author Michael Strand, at the University of Georgia…

Michael - Mosquitoes blood feed on different types of animals, including humans. But after they blood feed, they lose interest in blood feeding again until they complete the formation of eggs, which is why mosquitoes actually blood feed at all. Blood, by dry weight, is almost entirely protein, and that protein is essential for egg formation in mosquitoes. Sugar is mainly used for energy for flight. It's kind of like taking an energy drink for a runner. And so males and females consume sugars mainly to extend their lifespan and to be able to fly.

Chris - Why not just feed on blood all the time though? Because if it's got lots of protein but also some sugars, you could just live on blood all the time. So why don't they do that?

Michael - The general thinking is that blood feeding, as you can well imagine, is also quite risky for female mosquitoes because they can get killed in the process of trying to do it. So there is intrinsic risk associated with blood feeding that likely has mitigated why blood consumption is restricted to this female specific activity as opposed to being a general source of nutrients for all activities. Feeding on sugars from flowers and the like, is a much more low risk occupation.

Chris - So it makes sense then to have this sort of switch. When I need to lay eggs, I go for blood. When I'm not doing that, which is a metabolically demanding activity, I go for the low risk option. Those are the sugars.

Michael - That would be conventional wisdom. Yes.

Chris - And have you got a handle now on how you think they're doing this?

Michael - We have a handle, or at least some new insights, about what motivates females in terms of blood feeding. And maybe a convenient way of thinking about it is that just like human beings we have periods of having a strong appetite, we're very hungry. And then after we consume a large meal, we are dissuaded from feeding further. In other words, we're satiated or we're full. What we've identified is two hormones that control the motivation of having a strong appetite before blood feeding and another set of hormones that convey a sense of satiation or fullness to mosquitoes after they blood feed.

Chris - What are the hormones? Where are they and how do they work? How did you show that, that this is what's going on?

Michael - These hormones are very short proteins and we had antibodies which could bind to these peptides and they would provide a marker so that we could see them in the mosquito's body. And we used these to be able to determine that one of the hormones is produced in a type of cell in the gut of the mosquito. And that hormone is called neuropeptide F or NPF. And the other hormone is called RYamide and it's produced in neuronal cells that send projections to contact the gut and then we could monitor their production and loss before a blood meal and after.

Chris - So which one does the blood meal turn on and which one does it turn off?

Michael - NPF is on before blood feeding and is very quickly turned off after blood feeding. And reciprocally, RYamide is essentially off before blood feeding and is very strongly turned on after a female consumes a blood meal. So that means NPF functions as a promoting appetite and RY amide functions as suppressing appetite or giving a sense of being full. And we were able to show that because we could make these hormones and we could treat mosquitoes, we could eliminate the endogenous source of the hormone and we could replace it kind of like therapy and demonstrate that they had these functions experimentally.

Chris - Does this mean they're potentially a target? Then If we could go after these, can we try to dissuade mosquitoes from feeding on us?

Michael - That would be a long-term aspirational goal. And there's precedent for using hormones in this way. A very important class of drugs that are used as weight loss control drugs today are administered to people and they suppress appetite. And so one could imagine that molecules like this could be potentially delivered to mosquitoes and manipulate their behaviour.

Chris - There's some evidence that mosquitoes are the most dangerous animal on the planet because they spread all kinds of diseases. Things like malaria, things like the various viruses that we get from them, some of these diseases when the mosquitoes acquire them, change the behaviour of the mosquito and they make them bite more often. So is there any evidence that these diseases might be working through these hormone systems you've discovered and make the mosquitoes more likely to pass on the bugs they're carrying?

Michael - You're fully correct that pathogens mosquitoes acquire can manipulate the behaviour of mosquitoes and it's reasonable to speculate that one means of the way pathogens could manipulate mosquito behaviour would be by modulating these kinds of hormones.

Chris - So you're going to have to come back in a year or two and tell us if that's the case.

Michael - Yeah, I would very much hope that we could do that.

Chris - I want to be on the paper if I'm right.

Michael - <laugh>. Absolutely. At minimum in the acknowledgements. <laugh>

Chris - We'll talk to you in a year or two then Michael.

Michael - All righty.

Royal Society exhibition

Royal Society Summer Science Exhibition 2024
Ryan Bower, Imperial College London & Ben Moat, University of Southamption & Gilly Forrester, University of Sussex

The Royal Society's Summer Science Exhibition has been taking place in the heart of London. It’s a free event and no ticket is required, and it’s all about showcasing the best of British science. James Tytko went along…

James - You join me at the Royal Society's Summer Science Exhibition showcasing some of the cutting edge research from across the UK. I'm here in the main hall, eager to chat to some of the participating scientists to hear all about their projects. Hopefully I'll be able to catch them as I'm wandering through and I'll take you with me. Hi, nice to meet you. I'm James from the Naked Scientist Podcast. What's your name?

Ryan - I'm Ryan.

James - Could you sum up in a sentence for me the exhibit you brought to the exhibition today please?

Ryan - Yep. So we are engineering atom by atom. We're a collaboration between the University of Manchester, Leeds and Imperial College London. And we are showing how we can use ion implantation to create the materials of the future today.

James - Amazing. I mean engineering atom by atom. So literally taking apart or putting together individual atoms.

Ryan - That's right, yes. So we can take a single atom, we can charge it to create an ion and then we can position that into another material with very high accuracy. And that allows us to create new applications such as quantum computers, topological insulators, or single photo emitters.

James - It's absolutely mind blowing to me that engineering something so small can have ramifications for how we interact with our physical world.

Ryan - Yeah, it's really exciting as well to be doing that. And it does change the material properties so we can put in individual ions and then collections of ions that will change the material properties in ways that we can measure as well.

James - I know quantum computing's a highly hyped field. What are the main challenges with achieving what it's going to be able to unlock for us?

Ryan - So we are working on atom resolution, so a hundred thousand times smaller than the width of a human hair. And what we can do is we can also make these materials for our sources. So if we are implanting an ion, we need to have an alloy that will be stable and allow us to create that ion and then implant it into our material. So there's lots of scientists working on this project to allow us to improve the capabilities of this tool.

James - Alright. Well it sounds terrific. Thanks so much for chatting with me. Have a nice rest of the exhibition.

Ryan - Thank you. You enjoy it.

James - Hi, I'm James from the Naked Scientist Podcast. Can I get your name please?

Ben - So, I'm Dr. Ben Moat from the National Ocean Center in Southampton. So, our planet is warming at present, the ocean is absorbing 90% of this excess heat, this sort of anthropogenic heat that we and our ancestors, with CO2, have put into the atmosphere.

James - How on earth do you measure something like that 90% figure? Can you, can you expand on the methodology there?

Ben - So, since 2000 we have this program, this big international program called Argo. And we use these robots that basically measure the ocean for up to five years and they measure the top 2000 metres of the ocean. So we measure the temperature of its salinity and we transmit that data back every 10 days. So sea surface temperatures are rising. So we've all heard about coral bleaching. So the Great Barrier Reef, for instance, is dying, but there are other consequences as well. As the oceans get warmer, it can hold less oxygen. 50% of the oxygen we breathe comes from the ocean, but also 30% of that excess CO2 is going to the ocean that is then changing its pH. So that means it's harder and harder for these animals that build shells up around themselves to form. So there's a whole impact for the whole food chain.

James - How are these findings that you've acquired through these techniques going to lead to things we can do, actions we can implement to improve that situation.

Ben - So what we need is a large coupled ocean atmosphere, these big mathematical models to try and look at how it's gonna change in the different CO2 scenarios, carbon dioxide futures. We make the observations, we see how it's changing. We use those observations to benchmark or basically truth, these big ocean models.

James - Terrific. Well thank you so much for your time. Have a lovely rest of the exhibition.

Ben - Thank you very much. Thank you.

James - Hi, I'm James from the Naked Scientist Podcast. Can I get your name please?

Julie - I'm Professor Julie Forrester from the University of Sussex.

James - Tell me about Baby Boogie. What's the project?

Julie - So babies from birth have what we call rising movements and they're kind of like a belly dancer. They've got their arms and their legs going all at the same time. You see this kind of really smooth movement throughout the body. And it's, it's relatively constant. There'll be bursts of it and then it will calm down and burst again. And we can see different kinds of features in this writhing movement. Clinicians have known for a long time that children who are in high risk clinics, maybe they've had trauma at birth, that they can tell whether or not that repertoire looks healthy or poor. In talking with the clinicians and trying to better understand what they see in poor repertoire and good repertoire, we've learned that the complexity and the variability of infant movements seems to associate with their cognitive development. So good high variability and complexity tends to associate with healthy cognitive development.

James - So we might see language development skills come a lot later in babies who would otherwise have those more fluid movements that you were talking about.

Julie - So not even necessarily later, but possibly disrupted if we see poor repertoire. And so the idea is that right now our screening for autism and other neurodevelopmental disorders tends to be quite late. We wait until we see a deficit or with language or social behaviour. And so our diagnoses end up being two years, three years, four years, or even later. But what we think now we can do is find earlier risk markers that are visible and present within the motor behaviour of babies from birth. The Baby Grow project is already revealing promising results. We're seeing that babies in the first eight weeks of life are already showing differences in the high and low risk groups.

James - What are the benefits to those babies of understanding these developmental concerns as early as possible? How does that help you help them?

Julie - Oh, great question. The idea is that the earlier we can see risk factors, the earlier we can get in there and have new interventions. We don't have those interventions yet. They're things we need to develop, but we can develop motor interventions that help mitigate against some of those more severe language and social disorders that might happen otherwise.

James - Well, good luck with it. Thank you so much for your time. Been a pleasure.

Julie - Thank you so much.

James - Big thank you to everyone that's given me some of their time. Signing off from the Summer Science Exhibition here at the Royal Society. Get down here if you get the chance.

A sinkhole

What are sinkholes?
Vanessa Banks, British Geological Survey & Grady Hillhouse, Practical Engineering

You may have seen recent footage of a sinkhole appearing on a large football field in Illinois. The hole - which is 100 feet wide and 50 feet deep - swallowed the flood lights, benches and even the football pitch’s turf. But what exactly is a sinkhole? Here’s Vanessa Banks from the British Geological Survey…

Vanessa - A depression in the ground that doesn't have a surface drainage outlet, and therefore this depression is draining only from its space. The depression in the ground may have formed because of the lowering of the ground surface, because at that point there are soluble rocks. And a soluble rock is one that dissolves a bit like sugar in water when you pour slightly acidic water over it for prolonged periods of time. And as the hollow forms, then more and more water is focused to that point, and the dissolution extends to greater depth. And then we have something that we might call a dissolution sinkhole.


So, can anything be done to prevent them from swallowing up the ground and might they actually have a practical purpose in some cases? We put in a call to civil engineer and science populariser Grady Hillhouse, who is best known for his youtube channel Practical Engineering…

Grady - There are lots of areas across the world that have the specific geology that's conducive to sinkholes and there's really not much you can do to stop the problem. Right. It's very insidious. It's wide scale. So in that way it's kind of threatening. But also if you zoom out and look, we don't see that many sinkholes that cause real problems in the world. And so they're kind of rare, but also, you know, it's a widespread problem. <laugh>

Chris - So dramatic when it happens, but thankfully fairly infrequent at the moment. <laugh>. When it does happen, is there anything from an engineering point of view we can do that either we know will make the problem worse, so we know what to avoid doing? Or if we build buildings, build roads, put in infrastructure in a certain way, even if there is a sinkhole in the vicinity, we're a bit more resilient?

Grady - Yeah, definitely. The first step of that is just identifying the hazard. And so a big part of engineering in places that experience sinkhole is just characterising the hazard, right? And usually that involves drilling bore holes to take a look at the subsurface, see if there are caverns, see if there's limestone or gypsum or salt or human made things like mines that could pose a hazard to a structure. And then once you understand that hazard, then you can make a decision about what to do about it. Maybe that means relocating a structure from where you originally intended to put it, or it could also mean building stronger foundations that you know, can withstand a little bit of movement, a little bit of settlement, or even bridge a gap that might form over time.

Chris - So if we know there's a risk in a certain area and we have some plans to do some building there, is there anything we can do to almost put sensors in or anything like that so we can tell how fast things are moving, when things are on the move, and therefore when to watch out?

Grady - Yes and no. There's definitely opportunities to instrument buildings and structures and we do it all the time, right, to keep track of how a structure's performing over time, whether it be movement or expansion or contraction or cracks or how groundwater is flowing. So we do that, not just for sinkholes, but for all kinds of things. But sinkholes are a little bit different in that a lot of times it's a very, very slow process that culminates in this really dramatic collapse. And so it's much harder to kind of predict that very last part of it.

Chris - I suppose one of the issues here is that most big cities sprung up because there was an abundance of mineral resources or something else people could get from the vicinity where that city grew from. And often that was stuff underground, which means most big cities, certainly from days gone by, were on top of resources that people mined out. So we kind of made a rod to beat our own back, haven't we? Because <laugh>, we've got a city there because it was in an area that was plentiful for something we wanted. But the legacy of that is we are now building on land that we've turned into a honeycomb.

Grady - Yeah, I definitely think that's the case. In some places. There are also human made causes of sinkholes. For example,drainage and sewer pipes can get a crack and start eroding soil into the inside. And so oftentimes you'll see a sinkhole that opens up in the middle of a road that has nothing to do with geology at all, right? It's all about a failure of a sewer or water pipe that's eroding the soil and moving it away from the subsurface.

Chris - Is anyone trying to do anything practical with a sinkhole? So if we know that one is coming or one has happened in an area, it sort of saves us from making a big hole in the ground. It strikes me. So is there anything that people are saying, well, this could actually be useful?

Grady - That's a good question. There are definitely examples where natural drainage will flow into a sinkhole and that can be useful to recharge an aquifer that may be used as a water supply. I'm trying to remember the Arecibo telescope in Puerto Rico that was formed in a big basin and I can't remember if they would call that a sinkhole or not, but that was an example of using the natural topography to the advantage of creating a big radio reflector.

A leaf

Why aren't plants damaged by UV light?

Thanks to Gareth Jenkins for the answer!

Gareth - The answer is that plants have evolved very effective ways of protecting themselves from the harmful ultraviolet radiation in sunlight that causes sunburn and melanoma in humans. Although we humans can shelter from bright sunlight, exposure to UV radiation is an unavoidable hazard for plants. They need to be exposed to sunlight for photosynthesis, which fuels their growth. Plants avoid damage by sunlight in three main ways. Firstly, they reflect it by having a waxy coating and hairs on the surface of leaves. But this reduces light exposure in general and doesn't prevent UV exposure specifically. Second, plants actually make their own sunscreen and deposit it in the outer tissues. These sunscreen molecules work in the same way as our sunscreen by selectively absorbing UV wavelengths.

James - Well, that's a whole lot more convenient than applying sunscreen out of a bottle and now for that other solution.

Gareth - Thirdly, plants have effective mechanisms to repair any damage to their cells caused by UV exposure. An important feature of all these protective mechanisms is that they're stimulated when plants are exposed to UV radiation. Even very low levels of UV, such as found on a dull winter's day in the UK, are sufficient to stimulate production of the sunscreen and UV repair mechanisms. This ensures that protection is already in place when plants are subsequently exposed to high levels of UV in bright sunlight. Remarkably, plants can detect the presence of UV using a photoreceptor protein, and this causes genes to be activated that enable production of the sunscreen and damage repair mechanisms. So plants are able to avoid damage in sunlight through genetic processes, stimulated by their ability to sense and respond to UV light.

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