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What did the project achieve?
“Our work has revealed new insight into the underlying biology of Diamond-Blackfan anaemia, which could lead to improved diagnosis and new treatments for children and their families affected by this condition in the future,” says Professor John Strouboulis of King’s College London.
Diamond-Blackfan anaemia (DBA) is a rare genetic condition where a child’s bone marrow fails to produce enough red blood cells. As a result, they can’t carry enough oxygen around their body – leading to severe anaemia. Currently, haematopoietic stem cell transplantation is the only cure for the condition, but carries significant risks – and long-term treatment involving regular blood transfusions or steroid drugs can cause complications.
Researchers have previously identified several faulty genes that cause DBA, most of which carry the instructions to build tiny structures called ribosomes – which are the cell’s protein-making factories. Faults in the ribosomal protein (RP) genes lead to low levels of a protein called GATA1, which is essential for the production of new red blood cells. In rare cases, faults in the GATA1 gene that lead to a shortened version of the GATA1 protein, have also been associated with DBA.
This research aimed to understand how these faulty genes and proteins work together to interfere with fundamental biological processes in the bone marrow that generate red blood cells, leading to DBA.
“We initially discovered that more than 70% of RP genes may be switched on by GATA1 in red cells grown in laboratory dishes,” says Professor Strouboulis. “In further experiments, we showed unequivocally that GATA1 controls the activity of RP genes that we tested in these cells – and disrupting this process affects the production of red blood cells and proteins.”
The team also carried out a series of experiments that showed that introducing the faulty version of the GATA1 gene into red cells leads to severe problems with red blood cell production and high levels of cell death.
“Action funding was very important because it allowed us to explore a new area of research in DBA to better understand the molecular pathways of the disease,” says Professor Strouboulis.
“Our findings led us to design a new test to screen for faults within the control switches of the RP genes that are targeted by the GATA1 protein. This could pave the way to improved diagnosis for the one in three children with DBA who do not currently have a confirmed genetic explanation.”
This research was completed on
Diamond-Blackfan anaemia (DBA) is a rare genetic condition where a child’s bone marrow fails to produce enough red blood cells. Affected children are usually diagnosed with severe anaemia in their first year of life. Currently, there is no cure and long-term treatment involving regular blood transfusions or steroid drugs can cause complications. Professor John Strouboulis of King’s College London is aiming to improve understanding of the underlying biological causes of the condition. This work could ultimately lead to new treatments – and improved diagnosis for around three in 10 children with DBA who do not currently have a confirmed genetic explanation.
How are children’s lives affected now?
Children born with DBA have problems with the production of red blood cells. As a result, they can’t carry enough oxygen around their body – leading to severe anaemia.
“An affected child will experience symptoms such as tiredness, breathlessness, headaches and pale skin,” says Professor Strouboulis. “Around half also have physical changes when they are born – and they are often short for their age and may have delayed puberty.” Children with DBA also have an increased risk of developing cancer later in life.
Researchers have identified several faulty ribosomal protein (RP) genes that cause the condition, which account for around seven out of 10 children with DBA. Most of these genes code the building blocks for tiny structures in cells called ribosomes, which process the cell’s genetic instructions to make proteins.
“If a cell’s ribosomes aren’t working properly, this leads to low levels of a protein called GATA1 that is essential for producing new red blood cells,” explains Professor Strouboulis.
Rare faults in the GATA1 gene itself have also been found in DBA patients, further highlighting the critical involvement of this protein in this type of anaemia.
How could this research help?
“We aim to improve understanding of the biology of DBA – and to identify other faulty genes that cause the condition,” says Professor Strouboulis.
The researchers have found evidence suggesting that the GATA1 protein, as part of its role in red blood production, may also be involved in controlling genes that build the ribosomes themselves.
“We will carry out laboratory research to find out whether the GATA1 protein directly controls ribosome production in red blood cells – and if rare faults in this gene found in patients affect this process, leading to DBA,” says Professor Strouboulis.
The team will also explore the development of a new test that can identify faults in ribosomal genes switched on by the GATA1 protein that may account for some children with DBA who currently have no genetic diagnosis.
Building knowledge about the underlying causes of anaemia in DBA could lead to new treatments and improved diagnosis for children and their families affected by this condition.
Research table
Project details
| Project Leader | Professor John Strouboulis, PhD |
| Location | Comprehensive Cancer Centre, Rayne Institute, King’s College London |
| Project Team |
Dr Barnaby E Clark, PhD
Dr Helen Heath, PhD |
| Other Locations |
Precision Medicine, King’s College Hospital
Comprehensive Cancer Centre, Rayne Institute, King’s College London |
| Grant Awarded | |
| Grant Amount | £96,205 |
| Start Date | |
| End Date | |
| Duration | 24 months |
| Grant Code (GN number) | GN2866 |
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