Right place, right time: a closer look at DNA folding
Your body is made up of trillions of cells, all with the exact same DNA code to make you, you. But all our cells have different jobs – red blood cells deliver oxygen around the body, stomach cells break up your food and heart cells keep you going. So how can the same set of instructions lead to such different roles? And what impact do mistakes in these instructions have on human health? In this blog, Caz Harrold explains the science that underpins our Royal Society Summer Science Exhibition stand.
Each cell of the body contains a large amount of DNA – if you were to uncoil the DNA found in a single cell and stretch it out, it would be roughly 2 metres long! However, cells are very small and can usually only be seen under a microscope. So, how does 2 metres of DNA fit itself into a structure that is ten times smaller than a human hair?
DNA fits into a cell because of the way it is packaged and folded. This folding happens in a very specific and regulated way, and plays an important part in making different cells with specific roles. Genes are small sections of DNA that hold the instructions to make proteins – the building blocks of life that allow cells to perform their specific functions. Red blood cells produce a protein called haemoglobin, which latches onto oxygen, while stomach cells produce proteins called enzymes than chew up your food.
But while your genes (all 20,000 of them) take centre stage in everything you do, they only make up 2% of your DNA code. Most DNA acts in a regulatory manner, behaving as switches that can turn genes on or off, either making proteins or not. It’s the different combinations of genes which are either on or off at specific times that makes different types of cells. It’s this regulatory DNA that our team are interested in, as we try to uncover how faults in DNA can lead to disease.
In a lot of cases, the switches that control the genes are located very far away from each other along the DNA molecule. It’s the folding of the DNA that can bring them together and allow them to interact. However, the mechanisms of how DNA folds itself are still not fully understood. When this folding goes wrong, and the correct switches aren’t interacting with the correct genes, it can lead to diseases such as anaemia.
New technologies, called chromosome conformation capture techniques, have allowed us to study the 3D structure of DNA. This allows us to look at which exact bits of DNA are touching. We’ve used this technique to identify faults in folding in blood diseases, and we’re now using it to understand whether similar faults play a role in more common diseases such as diabetes. If we can find the problem, then we might be able to fix it with DNA editing techniques.
To uncover the genetics behind common diseases, we need to know more than just the DNA sequence. We need to understand the mechanisms and rules of DNA folding, and investigate the impact it has on switching the right genes on or off in the right cells at the right time. By combining expertise from biologists, medics and computer scientists, we hope to not only better understand human disease, but provide new options for treatments.