Research projects
I. Determining the DNA damage network that drives repeat expansion in Huntington’s Disease
Huntington’s Disease (HD) is a fatal autosomal dominant neurodegenerative disease caused by unstable expansion of a CAG triple nucleotide repeat in the coding region of the HTT gene. Currently there is no treatment that can slow or stop disease initiation or progression, thus there is an unmet need that could only be resolved by research aimed at discovering disease modifiers prospective to become used in therapy. Large HD population studies (GWAS) have recently uncovered that the expansion of repeats is strongly modified by two distinct DNA damage and repair (DDR) modules, FAN1 and mismatch repair (MMR). While the distinct connection between FAN1 and MLH1/MSH3 members of MMR is on scrutiny by us and others, we hypothesize that the repeat expansion is driven by a broader interaction network that has FAN1 as central node and we aim to uncover it. The current research builds on the successful implementation of a high-thruput CRISPR-CAS9 screening strategy and the important observation on the best cellular systems that can be used for such work. Based on this proof of principle to accomplish our overarching aim, we are proposing to:
Contract nr.760114/23.05.2023, code CF 66/14.11.2022. |