DBA Research UpdateDBA Research UpdateDR BETH PAYNE
Researching what goes wrong in DBA – WHAT DO WE KNOW?
•Mistakes or absence one copy of a group of genes•These genes code for ribosomal proteins
US National library of Medicine
Researching what goes wrong in DBA – WHAT DO WE KNOW?
• Red blood cells die prematurely
Researching what goes wrong in DBA – WHAT WOULD WE LIKE TO KNOW?
•Since ribosomes are needed in all cells, why does DBA mainly cause problems with red blood cells?
How to answer our questions?
• Patients and their families are the greatest teachers
• Some experiments cannot be done on patients so we need to learn more using other laboratory models
Zebrafish
Why do we use zebrafish?Why do we use zebrafish?
2mm
Effects of Leucine in DBA zebrafish
How l-leucine alleviate anaemia in DBA fish?
• We think L-leucine switches on production of ribosomal proteins
• This may be important in patients with DBA because they have a missing or defective copy of a RP
How does this happen?
RPS19 messenger RNA5’TOP
This part controls how much protein is
made
This part controls how much protein is
madeThis part actually
codes for the proteinThis part actually
codes for the protein
Increasing production of Ribosomal proteins
RPS19 messenger RNA5’TOP
We made a fish to test this
Express in Blood GFPTOP
Checking out the theory
The Goal
• Confirm how L-Leucine works to alleviate anaemia in DBA in humans
• Use the zebrafish we have generate to screen for new drug treatments that work in this way
AcknowledgementsUCL
Maria Virgilio
Greg Pietka
Youngrock Joung
Tariq Enver
Steve Wilson
David Linch
St Marys/Imperial College
Josu De La Fuente
DFCI/Harvard Medical School USA
Tom Look
Evisa Gjini
Ujwal Pyati
Hong Sun
Arati Khanna-Gupta
Nancy Berliner
Anu Narla
Ben Ebert
DBA Patients and families!!!
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