Science and the single cell
Our bodies are made up of trillions of cells - but these aren’t mere biological building blocks, as inert as bricks. They’re constantly communicating and changing. So how do scientists measure this? Plus, you can now take part in an international survey about genetics knowledge, a GIANT study throws up new genes linked to height, and a romantic gene of the month.
In this episode
Spying on single cells
with Stephan Lorenz, Wellcome Trust Sanger Institute
The human body is an enormous conglomeration of trillions of cells, of probably thousands of different types, all working together. Advances in technology now mean that we can spy on their activity and behaviour, right down to the level of a single cell. Kat Arney took a trip to the Wellcome Trust Sanger Institute to meet Stephan Lorenz, head of the single cell genomics core facility, to discover why scientists need to get up close and personal with single cells, and how on earth they manage it.
Kat - Stephan Lorenz from the Wellcome Trust Sanger Institute. And now it’s time to catch up with the latest genetics news.
09:36 - All genes great and small
All genes great and small
An international collaboration of researchers has discovered 83 new genetic variations linked to human height, according to a paper published in the journal Nature. So far 700 genetic variations have been found that affect height, and these new discoveries add yet more information to the picture. The new findings come from the appropriately named GIANT study, or Genetic Investigation of Anthropometric Traits, involving more than 700,000 people.
The GIANT team previously used a technique called GWAS, or genome-wide association study, to link genetic variations at single DNA letters, called SNPs to height. In this study, they’ve turned to a more in-depth genetic analysis technique called exome sequencing - which looks at the whole DNA sequence of genes rather than snapshots of single letters - to find rare variations linked to height, which are found in less than 5 per cent of the population.
The study is an important proof of principle that this more detailed method can find new and rare genetic variations, as well as revealing the genetic pathways that help to control height.
10:50 - Gene editing fights leukaemia
Gene editing fights leukaemia
Doctors at Great Ormond Street children’s hospital in London are thrilled to announce that two baby girls with cancer, who were both treated with gene-edited immune cells, are doing well more than a year later, according to a report published in the journal Science Translational Medicine.
Back in November 2015, the team announced that a baby girl with leukaemia had been treated with an experimental therapy made from immune cells modified using new gene editing technique. Another baby girl was also treated in December that year, and both received the treatment as a last-ditch attempt when all other options had failed.
Known as CAR-T cells, the therapy involves modifying immune cells, known as T-cells, so that they spot cancer cells and destroy them. Many trials are underway around the world using modified versions of a patient’s own T cells, in order to avoid provoking an immune response against the therapy, although this level of personalisation makes the treatment very expensive and challenging to do. By using gene editing to knock out a gene in T cells that provokes the immune system, bulk-produced modified CAR-T cells can be given to any patient.
It’s not perfect, and just under 1 per cent of the modified T cells still stimulated an immune response, which can be very serious. But once it had settled down in the two treated babies, the modified T cells got to work killing their cancer cells. Further trials are now underway in other parts of the world, making this a hugely exciting area to watch for potential future cancer cures.
12:25 - Revealing rare disorders
Revealing rare disorders
Fourteen new developmental disorders have been discovered by a team led by researchers at the Wellcome Trust Sanger Institute, publishing their findings in the journal Nature this month. The Deciphering Developmental Disorders study - the largest of its kind in the world - has been analysing the DNA of thousands of children affected by previously undiagnosed rare genetic conditions, such as intellectual disability, epilepsy, autism or heart defects, along with their parents, in order to uncover the gene faults responsible.
On average, 1 in 300 children born in the UK have a rare developmental disorder caused by a new fault in a gene, adding up to 2,000 children a year in the UK. To find the genes responsible, the team screened all 20,000 or so human genes from more than 4,000 affected UK and Irish families, focusing their attention on new gene faults, or mutations, that crop up randomly as DNA is passed from parents to their child.
By matching up this genetic information with clinical records, the researchers were able to find children with new mutations in genes that had previously been linked to developmental disorders, but also managed to to spot 14 new developmental disorders that had been caused by spontaneous mutations in a child’s DNA and weren’t found in their parents.
Importantly, the study also revealed that older parents have a higher risk of having a child with a developmental disorder due to this kind of new, spontaneous mutation, with the chances rising from 1 in 450 for 20-year-old parents to 1 in 210 for 45-year-old parents. As part of the study, the researchers managed to provide a firm diagnosis for rare conditions affecting over a thousand children and their families - something that is very important for investigating potential treatments, informing the best clinical care, and getting access to additional health and educational support.
14:41 - Test your genetic knowledge
Test your genetic knowledge
with Robert Chapman, Goldsmith's University of London
Cast your mind back to the Naked Genetics podcast from June 2016, and you’d have heard Kat Arney interviewing Robert Chapman from Goldsmiths University of London about a pilot study he was carrying out to look at public knowledge and understanding about genetics - aiming to find out what people know, what they don't know, and what they think they know, as well as finding out if there are any gaps or areas of concern in specific age or ethnic groups.
Robert - So for example, do people from certain ethnic groups have different concerns to other groups - are there age differences, are there international differences, is the way that genetics is taught at school a predictor of concerns and things like that. So, we're really trying to do an empirical quantitative study, I believe for the first time, in the broad area of genetics. There has been research in this area, focusing on medical genetics, but not generally the issues that they apply across society so that's the new thing hopefully.
Kat - So everything from pea plants to pandas.
Robert - Exactly, yeah. I couldn't say it better.
Kat - So tell me a bit more about the study. What are you actually doing? What are you asking? Who are you asking?
Robert - So I can't give too much away because we've just piloted it and I'm hoping that some or all of your readers will be interested enough to engage with the study when it is published. But we're looking at what people know about genetics so there are general knowledge questions. We're looking at how they feel about genetics. So do they have concerns for example about genetically modified foods? We're also asking for information about their demographics. So this is very much a first stage. We're hoping to talk to as many people as possible. We're aiming for about 5,000 participants and stratified by profession and country. We're asking people whether they're parents or students so we can really build-up a picture of the demographics of our participants and see if there are any trends that we can spot which might help us target training material information more effectively.
Kat - I’m pleased to tell you that Robert’s full survey, the International Genetic Literacy and Attitude Survey, is now online at http://tagc.world/iglas/ - not only is it a fun quiz to test your genetics knowledge, but it’s providing important data to help the scientific community communicate genetics better in the future, so please do take a few minutes to fill it in. That’s http://tagc.world/iglas/
17:34 - Social lives of cells
Social lives of cells
with Alpha Yap, University of Queensland
Our bodies are made up of trillions of single cells all working together - common idea is that they are inert, almost like bricks. Alpha Yap, professor of cell biology at the university of Queensland in Brisbane, Australia, is keen to show that this idea of static cells simply isn’t true. Kat Arney caught up with him at the Royal Institution, where he was giving a lecture, sponsored by the Company of Biologists, entitled “Touching and holding: The social lives of our cells” to find out why.
Kat - Alpha Yap, from the University of Queensland in Australia, speaking to me at the Royal Institution. Thanks again to the Company of Biologists for sponsoring his talk.
27:07 - Gene of the Month - Panton-Valentine leukocidin
Gene of the Month - Panton-Valentine leukocidin
To celebrate Valentine’s day, for this episode's Gene of the Month we’ve picked the most romantic molecule we could find - Panton-Valentine leukocidin, or PVL. Unlike flowers, chocolate or sexy underwear, this is definitely not a gift that you’ll want to receive from your beloved, as it’s a potent bacterial toxin.
PVL was first discovered by Belgian researcher Honore Van de Velde in 1894, who was searching for chemicals produced by bacteria that could damage white blood cells, or leukocytes - important cells in the immune system. But it’s named after It’s named after Philip Panton and Francis Valentine, two scientists working in the 1930s who discovered that it was produced by strains of Staphylococcus aureus bacteria that caused the most severe infections in rabbits.
Further research revealed that PVL is made up of two proteins LukS-PV and LukF-PV, encoded by two separate genes. Together, they form a small pore in the wall of immune cells, causing their insides to leak out - something known as cell lysis. The contents of these sadly exploded cells than acts as tasty nutrients to feed the bacteria as the infection spreads. Intriguingly, the genes seem to have originally come from tiny viruses that infect bacteria, called bacteriophages.
Just as Panton and Valentine found that PVL-producing Staph. aureus produce nasty infections in bunnies, they also bring a lot of harm to humans, causing a type of necrotising pneumonia that can kill up to three quarters of patients. PVL-producing bacterial strains have also been pinpointed in many fatal bacterial outbreaks.
Given that PVL is found in the majority of antibiotic resistant Staph. aureus - the infamous MRSA superbugs - there’s a lot of interest in developing new treatments that block the toxin, which could combat the growing problem of antibiotic resistance. So although it may have Valentine in its name, PVL definitely isn’t something you’ll want to give the one you love this February.