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!!!