Dr Matthew Day

Matthew Day

Lecturer in Biochemistry

School of Biological and Behavioural Sciences
Queen Mary University of London
www.qmul.ac.uk/sbbs/staff/matthew-day.html
Centre for Molecular Cell Biology
ORCID

Research

DNA repair, DNA replication, Cancer, Structural Biology, CryoEM, in silico modelling (AlphaFold)

Interests

DNA replication must occur once, and only once, during each cell cycle. In eukaryotic cells this process is carried out by the replisome, a massive protein machine with many components. The MCM helicase is loaded at origins of replication in an inactive confirmation and must be converted to its active form by a highly coordinated process of events for individual origins to fire and for replication to successfully progress. This is driven by the recruitment of additional protein factors and much of this control is aided by scaffold proteins, such as TOPBP1, bringing the required factors together at the right time. Our research seeks to understand how these factors assemble into functional replication complexes, with particular interests in DNA polymerase ε (Pol ε), clamp loader complexes, and the molecular mechanisms that coordinate DNA synthesis

As well as having to be duplicated, the DNA in our cells is subject to damage every day and must be repaired to maintain genomic stability. To preserve genome stability, cells employ sophisticated DNA damage response pathways that detect lesions, signal their presence, and coordinate their repair. A major focus of our work is the 9-1-1 checkpoint clamp, its specialised loader complex, and its associated signalling network, including the scaffold protein TOPBP1.

The Day Lab aims to uncover the molecular mechanisms that govern DNA replication, DNA damage signalling, and genome maintenance. We combine structural biology approaches, including cryogenic electron microscopy, X-ray crystallography, and computational modelling, with biophysical methods such as fluorescence polarisation, Microscale Thermophoresis and isothermal titration calorimetry, alongside a broad range of biochemical and molecular biology techniques, to determine how dynamic protein assemblies are built, regulated, and coordinated. Our research is highly collaborative, working with others to bring together expertise in structural biology, cell biology, biochemistry, and biophysics to address fundamental questions in chromosome biology and genome stability.