Mechanisms of gene repression in erythroid cells

Funded Activity Summary

Inherited disorders of the blood, such as sickle-cell anaemia and thalassaemia, result from mutations in the genes that produce haemoglobin. Current treatments can partially alleviate some of the debilitating symptoms of these diseases but these treatments have significant side effects, and despite the best efforts of clinicians, many patients succumb to their conditions at an early age. It has been observed that certain individuals exhibit a milder form of the disease, as a consequence of the reactivation of their foetal haemoglobin genes, (a distinct set of genes that would have been active in utero but are normally silenced around the time of birth). It is widely accepted that if pharmaceutical means can be found for reactivating the foetal haemoglobin genes then many patients would benefit. The regulation of the foetal globin genes, like most human genes, is complicated and there are few obvious means of increasing their activity. Nevertheless, it is believed that by investigating the molecular mechanisms by which they are controlled it will be possible to devise therapeutic agents that mimic these mechanisms or to develop agents that prevent the shutdown of the foetal genes around birth. To this end we have been working on the molecules that regulate the activity of the haemoglobin genes. We have recently cloned a number of DNA-binding proteins, and their co-factors, that appear to be involved in silencing foetal globin gene expression. This grant proposal is concerned with learning how these new molecules operate to silence gene expression as a first step towards designing agents that will prevent the silencing.

Funded Activity Details

Start Date: 01-01-2000

End Date: 01-01-2002

Funding Scheme: NHMRC Project Grants

Funding Amount: $233,656.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Gene Expression

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

DNA-binding proteins | haemoglobinopathy | repression of gene expression | sickle cell anaemia | thalassaemia | transcription factors

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