High-performance computing server for visualising the molecular mechanisms of eukaryotic DNA replication

Name of applicant

Thomas Charles Richard Miller

Institution

University of Copenhagen

Amount

DKK 286,324

Year

2021

Type of grant

Research Infrastructure

Summary

We study how DNA replication can be a source of genomic instability and human disease. Our genomes are duplicated by complex molecular machines (replisomes), which frequently encounter naturally occurring 'obstacles' that can impede their ability to accurately copy DNA. A failure to overcome these obstacles can result in genome instability and age-related disorders including accelerated neurodegeneration and cancer. Using complementary electron and optical microscopy approaches, and a new high-performance computing server for data analysis, we will study replisome function at resolution scales ranging from atoms to cells. Our work will reveal how replisomes overcome DNA-bound obstacles and other sources of replication stress, and how these processes can fail, leading to human disease.

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