Transcript Slide 1

DBA Research Update
DR 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?
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?
This part
controls how
much protein
is made
5’TOP
This part
actually codes
for the protein
RPS19 messenger RNA
Increasing production of Ribosomal proteins
5’TOP
RPS19 messenger RNA
We made a fish to test this
Express in Blood
TOP GFP
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
Acknowledgements
UCL
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!!!