Histone acetyltransferases (HATs) and their antagonists, the histone deacetylases (HDACs), are important enzymes in epigenetic gene regulation. They control the chemical conversion of nuclear proteins, the histones, which are the major protein components of chromatin.
The research project of Wolfgang Sippl and Manfred Jung focuses on the computer-assisted screening of potential HAT inhibitors and the synthesis of new active substances that will then be tested in the test tube for their ability to block HAT. Subsequently, the inhibitors will be tested for their inhibitory effect on the growth of cancer cells in culture dishes and suitable candidates identified and further characterised. The work is being carried out in close cooperation with Dr. I. Fichtner from the Max Delbrück Centre for Molecular Medicine and Prof. Dr. M. Hendzel from the Cross Cancer Institute in Edmonton, Canada. The researchers are also focusing on the visualisation of what happens when histones are modified. The modification of cancer cell histones can be made visible under the fluorescence microscope using dye-labelled antibodies against acetyl groups. This helps the researchers to find new selective and potent HAT inhibitors in order to evaluate their therapeutic potential. Many more years of research will certainly be needed before the inhibitors can be used for the treatment of cancer patients.