Tian Qiu

Profile

Project Title: The role of the chromatin modifier Kdm2aa in melanoma formation

Summary:

Kdm2aa is an orthologue of the human chromatin modifier KDM2A. Loss of Kdm2aa in zebrafish causes Braf^V600E-independent spontaneous melanoma and other phenotypes such as fin regeneration and oogenesis defects. Our Kdm2aa^sa898 and Kdm2aa^sa9360 mutants have premature stop codon alleles due to point mutations. Kdm2aa^sa898 is assumed to produce a non-functional protein, and Kdm2aa^sa9360 may produce a partially functional protein. However, which protein domains in Kdm2aa are required to prevent the melanoma phenotype is not known. GO analysis of genes differentially expressed in mutants as determined by RNA-seq revealed enrichment of genes related to DNA replication, translation, and chromosome organisation, especially DNA double strand break (DSB) and chromatin modification, which is in accordance with the role of Kdm2aa in chromatin regulation.

This research project will study the role of chromatin maintenance in cancer formation. Using CRISPR/Cas9 in wild-type zebrafish to generate zebrafish lacking specific protein domains of Kdm2aa, the project will determine which domains of Kdm2aa are required to suppress tumour formation. Functional assays and in vivo protein stainings will elucidate which DNA damage signalling and repair pathways are affect by Kdm2aa loss of function. Zebrafish melanoma tissues will firstly be separated by specific melanoma markers, and then functional genomics approaches such as ATAC-seq and CUT&RUN will be applied to study chromatin changes in the tumour tissue compared to normal tissue in zebrafish.

Supervisor:

• Dr Elisabeth Busch-Nentwich

Research