Structural and functional basis of chromatin remodelling

In eukaryotes, DNA is made to fit inside the cell nucleus through a high degree of compaction that is enabled by assembly into chromatin.
 
Processes such as DNA damage repair and transcription require localized changes in chromatin compaction. Cells have multiple molecular strategies to control this. In one, multi-protein chromatin remodelling complexes use the energy from ATP hydrolysis to alter DNA compaction. Among them, the mSWI/SNF complex is of special interest because several subunits, including  components of yet unknown function are coded by genes mutated or mis-expressed in many forms of cancer.
 
The impact of these cancer-associated mutations on mSWI/SNF assembly and function, and on the cancerous phenotype, is mostly unknown.
 
By combining cryo-electron microscopy, x-ray crystallography, molecular biology and biochemistry we will gain understanding of this complex at the molecular and atomic level. Our expectation is that such information will contribute to the development of future therapeutic agents against cancer and other human diseases.