Characterization of novel Ikaros related proteins

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/211000

Funding Status
Closed

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Funded Activity Summary

DNA-binding proteins regulate gene expression and co-ordinate normal patterns of development. We are investigating a set of DNA-binding proteins, termed the Ikaros family. These proteins are known to be important regulators of white blood cell production and mutations that interfere with Ikaros activity are associated with aggressive childhood leukaemias that are resistant to treatment. Recently, it has become apparent that Ikaros proteins also regulate genes in red blood cells. One observation is that Ikaros plays a role in silencing the foetal haemoglobin genes. The haemoglobin genes have been extensively studied because diseases, such as beta-thalassaemia, which are caused by mutations in the adult haemoglobin genes, are among the most common genetic diseases known. One strategy to alleviate beta-thalassaemia centres around re-activating the foetal globin genes and thereby re-supplying globin to adults who have only mutant forms. In this context, the observation that Ikaros plays a role in foetal globin silencing is of considerable medical significance. We have recently identified two new regulatory proteins that are related to Ikaros and are found in red blood cells. Little is known about these proteins but they can directly bind to Ikaros and they are capable of silencing gene expression. We therefore wish to test the hypothesis that they work together with Ikaros to silence gene expression. Ultimately we expect that understanding how these proteins and Ikaros operate will suggest new strategies for re-activating the silent foetal globin genes to treat beta-thalassaemia, as well as preventing the proliferation of white blood cells carrying mutant Ikaros proteins.

Funded Activity Details

Start Date: 01-01-2002

End Date: 01-01-2004

Funding Scheme: NHMRC Project Grants

Funding Amount: $422,310.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Biochemistry And Cell Biology Not Elsewhere Classified

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

anaemia | gene expression | leukaemia | oncology | protein characterization | thalassaemia | transcription factor | transcriptional regulation | zinc finger proteins

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