Epigenetic Regulation Of Self Renewal And Lineage Commitment In Haematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$1,104,930.00
Summary
The process by which all our mature blood cells are produced and sustained remains largely unknown. Underpinning the cell fate decisions made through blood cell development is the tightly regulated expression of key genes and proteins that subsequently direct the process of blood cell differentiation. This project will aim study and uncover the molecular mechanisms that coordinate the key gene expression programs that lead to normal blood cell development.
We are seeking to understand how the protein ADAR1 functions. When it is mutated, ADAR1 can cause a range of diseases, most notably in a subset of Aicardi-Goutieres syndrome (AGS) patients, an autoimmune disorder affecting the brain, immune system, and skin. We have identified how we think that changes in ADAR1 activity may ultimately cause disease. This application will allow us to test this mechanism experimentally.
A New Function For Histone Variants In The Tissue-specific Regulation Of Pre-mRNA Splicing
Funder
National Health and Medical Research Council
Funding Amount
$657,224.00
Summary
It is estimated that greater than 90% of human genes undergo alternative RNA splicing, which can explain how protein diversity is achieved with a limited number of genes. However, how alternative splicing patterns are established remains poorly understood but is an important question given that 15-50% of human disease mutations are associated with changes to the splicing patterns of RNA. We have uncovered a new splicing mechanism, which involves changing the way DNA is packaged in a cell.