DBA Research Update DR BETH PAYNE Researching what

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? 2 mm

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 RPS 19 messenger RNA

Increasing production of Ribosomal proteins 5’TOP RPS 19 messenger RNA

We made a fish to test this Express in Blood TOP GFP

Checking out 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!!!