Walter and Eliza Hall Institute of Medical Research

Leigh Coultas

Lorraine Ann O'Reilly

Andreas Strasser

Hamsa Puthalakath

Grant Dewson

David Ching Siang Huang

Emma Watson

Jennifer Beaumont

Andreas Villunger

The specification relates to the use of Mcl-1 inhibitors to promote apoptosis in vascular endothelial cells undergoing neovascularisation in disease states.

Use of therapeutic agents

The present invention relates generally to novel molecules capable of, inter alia, modulating apoptosis in mammalian cells and to genetic sequences encoding same. More particularly, the present invention relates to a novel member of the Bcl-2 family of proteins, referred to herein as 'Bmf', and to genetic sequences encoding same and to regulatory sequences such as a promoter sequence directing expression of Bmf. Bmf comprises a BH3 domain which facilitates interaction to pro-survival Bcl-2 family members thereby triggering apoptosis. Bmf is regarded, therefore, as a BH3-only molecule. The molecules of the present invention are useful, for example, in therapy, diagnosis, antibody generation and as a screening tool for therapeutic agents capable of modulating physiological cell death or survival and/or modulating cell cycle entry. The present invention further contemplates genetically modified animals in which one or both alleles of Bmf are mutated or partially or wholly deleted alone or in combination with a mutation in one or both alleles of another Bcl-2-type molecule such as but not limited to Bim. The genetically modified animals are useful inter alia in screening for agents which ameliorate the symptoms of diseases caused by defects in apoptosis or which specifically promote apoptosis of target cells.

Bcl-2-modifying factor (bmf) sequences and their use in modulating apoptosis

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Melbourne, Australia

Leigh Coultas