Growing human hearts

Growing a human heart from a single cell may seem like science fiction, but scientists at the Gladstone Institute at the University of California San Francisco, have taken a huge step forward, by producing the first three-dimensional, beating, human heart chamber. Previously, it had been possible to produce a two dimensional sheet of beating heart cells, but to really gain an understanding of heart formation in a developing foetus and perhaps more importantly, how drugs given to women during pregnancy may affect this development, a three dimensional structure was needed. By treating stem cells with drugs and then confining them to a very small spherical geometry, Bruce Conklin and his team have managed to grow their very own three dimensional model of a human heart, as he explains…

Bruce – the cells around the edge became fibroblasts – a particular type of cell that you use to heal wounds and then only in the very centre were cardiac cells that beat. What this is forming is more of a little organoid is what we call it, where there’s beating cells but there’s also multiple other cell types and that’s what makes it so interesting is that these cell types are somehow talking to each other and somehow collaborating in some way so that they can actually make this structure that we didn’t expect.

Tom – It’s almost like they’re trying to form a heart…

Bruce – That certainly is the impression. They’re heart cells, they’re forming cavities so it could be a model of how parts of human development occurs, but it certainly is not a real human heart in the sense that there’s probably many things that we’re missing. We just have a simplified version with just one chamber, but having it in a controlled way where it happens the same way over and over again we can start asking questions about ‘how do these cells talk to each other?’ So once you have a system which is reproducible you can do experiments to break it in some way or to enhance it in another way.

Tom – What are the applications of this work then?

Bruce – The most obvious application of the work is to study human development. How do cells actually form a heart is something of basic interest. And also, the most common form of birth defects is actually cardiac defects. But the other application is that we can expose these developing human micro-chambers to drugs which are thought to cause developmental defects, specifically of the heart, and in fact one of the key experiments in this study was to use the drug thalidomide which is notorious for causing birth defects. When we expose these cells to the thalidomide they had a dramatic change in the morphology so that you could see that it was altering the developmental process in this micro-chamber. Thalidomide was tested in rodents before it was tried in people and there were no cardiac defects in the rodents. I think that more and more we’re thinking how do we get tests which use real human cells so that we can actually make safer drugs. And in this case say you turn back the hands of time and you had this sort of test perhaps you would have discovered that thalidomide was dangerous before it had gone on to be given to people.

You can listen to the full interview with the Naked Scientists here.

Oxplore: Do we see colour the same?

Livestream debate with researchers at the University of Oxford discussing the BIG question: do we see colour the same? Featuring an incredible trick with colour perception, a multiple choice question for you to try at home, and a discussion of the dress – is it blue and black or white and gold?

Can a pill make you fitter?

These days it seems that we are always hearing about the latest ‘wonder pill’ that will help you to get fit – often with very little science to back it up. Well, this time things are a little different. Scientists at the Salk Institute in California have discovered a new pathway used by the body during exercise and are able to recreate its effects in mice by simply giving them a pill. The mice were able to run for a much longer period of time and gained less weight! I spoke to senior researcher Weiwei Fan to find out how it all works…

  • The process involves a protein called PPL-delta which during exercise turns up the genes that burn fat and turns down the genes that burn sugar.
  • Mice that were given a chemical to activate the PPL-delta protein over an 8-week period could run for about 270 minutes, whereas mice that were not on the drug could only run for about 160 minutes.
  • The activation of the protein not only increases endurance, but by burning fat instead of glucose it can also result in weight loss, making it a possible treatment for type 2 diabetes, obesity and fatty liver disease.
  • On a high-fat diet, the mice with the drug gained 50% less weight than those without, with the weight loss occurring almost entirely in fat rather than muscle.
  • The ultimate goal is to test the findings in humans once the current negative side effects of the drug are eliminated.

 

 

 

You can listen to the full interview for the Naked Scientists here.

Plankton change genes to combat climate change

2016 was another record-breaker in terms of global temperatures, and it’s part of a longer-term trend which has seen 15 of the hottest years on record since 2001. One victim of this warming is the Artic. The sea ice is steadily retreating, which means that the habitats for species that live there are also radically altering. So are these organisms equipped to cope with the change? Thomas Mock, from the University of East Anglia, has been studying one marine species which use a genetic trick to adapt, as he explains…

Thomas – With our study we have provided first isights into the evolution adaptation of phytoplankton which are little plants floating in the ocean and we selected to sequence one of their genomes. It was a diatome, they prefer to live in nutrient rich and cold water and therefore their natural home are the polar oceans like the Southern Ocean and the Arctic Ocean. In polar oceans they are the base of the entire food web, including fish, birds and mammals like the polar bears and whales. So if their diversity changes according to global warming, which is a significant concern, then the entire food web might change with consequences for human societies.

Tom – You said that you’d looked at the genome of these phytoplankton – is that DNA sequencing?

Thomas – Yes, what we did is we selected one keystone species and we sequenced its DNA. And what we found is that they are very very different to anything that was sequenced before, at least form the marine system.

Tom – And those differences, are they because of the cold and variable environment?

Thomas – Yes that’s what we think. The variability of the polar oceans has basically caused or shaped the genomes of these organisms. What we’ve found is that the adaptation basically boils down to how they use their alleles. Alleles are basically different versions of the same gene. So in our genome we have two versions of each gene. One is derived from the mother and the other is derived from the father. They can be different from each other which impacts how we look. So I can give you an example, for instance the gene for eye colour has an allele for brown and for blue eyes. People can have two for brown, two for blue or a mix of both alleles. And this mix of alleles is basically what we found in our polar diatome genome, but not only for a small number of genes, but for 25% of all genes in the genome. These different versions are used under different environmental conditions.

Tom – So the phytoplankton are in some sense switching on the genes that help them to survive given the current environment?

Thomas – Yes that’s right – they switch on different versions of the same genes in different ways and this makes them able to cope with changing environmental conditions.

Tom – Could you give an example of one of these particular alleles that you found specifically in the phytoplankton?

Thomas – One group of genes we found is the group of antifreeze proteins. And they are expressed, they are used whenever temperatures drop below the freezing point of seawater. These creatures live between the ice crystals – this very very extreme habitat with high salinities and very low temperatures and they can cope in these extreme conditions very well because they have very different types of these antifreeze proteins.

Tom – I’m putting myself in the shoes of one of these phytoplankton. If I’m happily floating about in the sea and then suddenly the sea freezes and I become trapped in sea ice, would I then suddenly switch on this particular version of this protein to allow me to survive.

Thomas – Yeah that’s correct and this is what we actually tested in the laboratory. We simulated sea ice formation and then we looked at how all of the different genes in the genome are expressed.

Tom – Now that we now this, ultimately how is this going to help us, what does this actually mean going forwards?

Thomas – We hope that we can make predictions better about polar organisms cope with global warming. We have global warming and the most threatened ecosystems are polar ecosystems because they are the most sensitive – we see a retreat of sea ice and so on. What we didn’t know so far is how these organisms cope. What are the mechanisms that underpin how they can cope? And with our study we can say that they have a very broad tool set. To me it doesn’t seem to be all doom and gloom, they are very resilient to be honest. With our study we can say that they are very well equipped to cope with global warming and potentially also loss of sea ice.

You can listen to the full interview for the Naked Scientists here.

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