Crick News

ISSUE 32

September 2017

Science snippets

science-snippets-2-503x307px.jpg

New technique overcomes genetic cause of infertility

Scientists have created healthy offspring from genetically infertile male mice, offering a potential new approach to tackling a common genetic cause of human infertility.

Our sex is determined by the X and Y chromosomes. Usually, girls have two X chromosomes (XX) and boys have one X and one Y (XY), but approximately 1 in 500 boys are born with an extra X or Y. Having three rather than two sex chromosomes can disrupt formation of mature sperm and cause infertility.

In a new study published in  Science, scientists at the Francis Crick Institute have found a way to remove the extra sex chromosome to produce fertile offspring. If the findings can be safely transferred into humans, it might eventually be possible for men with Klinefelter syndrome (XXY) or Double Y syndrome (XYY) that are infertile to have children through assisted reproduction using this technique.

However, lots more research is needed before this approach could ever be used in humans. Senior author James Turner, Group Leader at the Crick, explains: "There is currently no way to make mature sperm outside of the body. In our mouse experiments we have to inject cells that have the potential to become sperm back into the testes to help them finish developing. But we found that this caused tumours in some of the mouse recipients. So reducing the risk of tumour formation or discovering a way to produce mature sperm in a test tube will have to be developed before we can even consider this in humans."

Scientists find new method to fight malaria

Scientists have discovered a new way to slow down malaria infections, providing a possible new target for antimalarial drugs. The team are already working with pharmaceutical companies to use this knowledge to develop new antimalarials - an important step in the battle against drug-resistant malaria.

When malaria parasites invade red blood cells, they form an internal compartment in which they replicate many times before bursting out of the cell and infecting more cells. In order to escape red blood cells, the parasites have to break through both the internal compartment and the cell membrane using various proteins and enzymes.

Scientists at the Francis Crick Institute and the London School of Hygiene & Tropical Medicine have identified a key protein involved in this process. Disrupting this protein reduces the efficiency of parasite escape, slowing down the rate of infection. The research, published in  PLOS Pathogens was funded by Cancer Research UK, the Medical Research Council and Wellcome.  

"The parasite sits in its internal compartment inside the cell, surrounded by lots of proteins, a bit like a baby surrounded by amniotic fluid," says Mike Blackman, Group Leader at the Crick. "We focused on the most common protein, known as SERA5, assuming that it probably has an important role since there is so much of it."

The team are now working with GSK to see if SERA5 or one of the enzymes that it controls could be a potential drug target.

"Drug resistant malaria is a huge problem, so there is a real push to develop new drugs that work in a different way," says Mike. "None of the current antimalarials work by preventing the parasites from escaping red blood cells, so we think that the proteins and enzymes that help the parasites break free could be valuable new targets that we can design drugs for."

Chemo-boosting drug discovered for leukaemia

Drugs developed to treat heart and blood vessel problems could be used in combination with chemotherapy to treat an aggressive form of adult leukaemia, new research led by the Francis Crick Institute reveals.

In a study published in  Cancer Cell, researchers at the Francis Crick Institute, King's College London and Barts Cancer Institute discovered that acute myeloid leukaemia (AML) ─ the most common acute leukaemia affecting adults ─ causes bone marrow to 'leak' blood, preventing chemotherapy from being delivered properly. Drugs that reversed bone marrow leakiness boosted the effect of chemotherapy in mice and human tissue, providing a possible new combination therapy for AML patients.

"We found that the cancer was damaging the walls of blood vessels responsible for delivering oxygen, nutrients, and chemotherapy. When we used drugs to stop the leaks in mice, we were able to kill the cancer using conventional chemotherapy," says Diana Passaro, first author of the paper and researcher at the Crick.

As the drugs are already in clinical trials for other conditions, it is hoped that they could be given the green light for AML patients in the future.

AML is relatively rare ─ approximately 2,600 people are diagnosed in the UK each year ─ but as it mainly affects people over 65, prevalence is likely to increase with an ageing population. It is a particularly aggressive cancer, with fewer than a quarter of patients living for five years after diagnosis. Chemotherapy resistance and relapse are a major problem in treating the disease.