Simon has a BSc in Biochemistry from Hertiot-Watt University (Edinburgh) and a PhD from the University of East Anglia (Norwich). Simon studied for his PhD at the John Innes Centre in Norwich under the supervision of Prof. J. Allan Downie, investigating the role of calcium signalling during legume symbiosis. It was during this time that Simon first used a confocal microscope, sparking an interest in microscopy and imaging technology.
Following his PhD, Simon went to work as a postdoc in Pete Cullen's lab in the Department of Biochemistry at Bristol University, investigating Ras GTPase-activating proteins. These studies required the use of various microscopy systems and cemented Simon’s passion for biological imaging. Simon moved to the 99ÈȾòÝÈÈ×îеØÖ· in 2004 where he established the Institute’s core Imaging Facility.
The Imaging Facility now provides state-of-the-art microscopy services essential for the delivery of Institute science and is an important Babraham Research Campus resource supporting the commercial research community.
The development of complex tissues relies on the precise assignment of cell identity. At the molecular scale, this process depends on the deposition of epigenetic modifications-such as methylation-that are regulated by complex biochemical networks and occur at specific regions on the DNA and chromatin. Here we show that despite the complexity of epigenetic regulation, dynamical scaling and self-similarity of DNA methylation marks emerge in embryonic development. Drawing on single-cell multi-omics experiments, super-resolution microscopy and statistical physics, we demonstrate that these phenomena originate in dynamical feedback between DNA methylation and the formation of nanoscale dynamic chromatin aggregates. These nanoscale processes lead to genome-wide increase in DNA methylation marks following a power law and self-similar correlation functions. Using this framework, we identify methylation patterns that precede gene expression changes in embryonic symmetry breaking. Our work identifies linear sequencing measurements as a laboratory to study mesoscopic biophysical processes in vivo.
TrAEL-seq is a robust method for profiling DNA replication genome-wide that works in unsynchronized cells and does not require drugs or nucleotide analogues. Here, we provide an updated method for TrAEL-seq that improves sample quality and includes multiplexing of up to six samples which dramatically improves throughput, and we validate TrAEL-seq in multiple mammalian cell lines. The updated protocol is straightforward and robust yet provides excellent resolution comparable to OK-seq in mammalian cell samples. High resolution replication profiles can be obtained across large panels of samples and in dynamic systems, for example during the progressive onset of oncogene induced senescence. In addition to mapping zones where replication initiates and terminates, TrAEL-seq is sensitive to replication fork speed, revealing effects of both transcription and proximity to replication Initiation Zones on fork progression. Although forks move more slowly through transcribed regions, this does not have a significant impact on the broader dynamics of replication fork progression, and instead replication forks accelerate across the first ∼1 Mb of travel irrespective of local transcriptional activity. We propose that this is a consequence of fewer replication forks being active later in S-phase when these distal regions replicate and there being less competition for replication factors.
We developed a 50-plex imaging protocol using the MACSima platform to characterize the microarchitecture of germinal centers in secondary lymphoid tissues. This workflow combines tissue processing, automated cyclic imaging, image preprocessing, and a new analysis method that detects morphological changes in irregularly shaped stromal cells.