Simon Andrews did his first degree in Microbiology at the University of Warwick. After a brief period working for Sandoz pharmaceuticals he went on to do a PhD in protein engineering a the University of Newcastle with Harry Gilbert. During his PhD his interests moved from bench work toward the emerging field of bioinformatics, and he decided to follow this direction in his future career.
After completing his PhD Simon worked with the BBSRC IT Services where he developed and then presented a series of bioinformatics training courses in protein structure analysis to the BBSRC institutes. At one of these courses at Babraham he met John Coadwell who establised the Babraham Bioinformatics group and was then employed as the second member of the bioinformatics team. Since joining Babraham Simon has seen the group grow from two people to nine as the field has become far more prominent in the biological research community. He took over the running of the group in 2010. Simon won a Papin Prize in 2025 for contributions to research (news article link).
The diversity of antibodies underpins robust immune responses. During the formation of the antibody repertoire in early bone marrow B-cells, random antibody heavy-chain proteins are generated from recombined VH, DH, and JH gene segments. Many are non-functional and are negatively selected. To understand this process in normal mice, we have undertaken an in-depth analysis of heavy-chain selection at this pre-B cell transition. We find independent selection acting on three regions of the complementarity-determining region 3 (CDR3) antigen-binding site, with particularly heavy counter-selection against certain productive VH/JH combinations. This led us to hypothesise that VH-replacement, where the VH gene segment in an existing VDJ combination is replaced, targets productive VDJ rearrangements that code for non-functional heavy chains. We detect VH-replacement recombination products that closely follow the pattern of selection of functional and non-functional VDJ rearrangements. This reveals a physiological role for VH-replacement in the developmental release of B-cells that are stalled by non-functional heavy-chains. This leads to re-modelling of the restricted early VDJ repertoire toward the use of other VH gene segments throughout the IgH locus.
Profiling combinations of histone modifications identifies gene regulatory elements in different states and discovers features controlling transcriptional and epigenetic programs. However, efforts to map chromatin states in complex, heterogeneous samples are hindered by the lack of methods that can profile multiple histone modifications together with transcriptomes in individual cells. Here, we describe single-cell multitargets and mRNA sequencing (scMTR-seq), a high-throughput method that enables simultaneous profiling of six histone modifications and transcriptome in single cells. We apply scMTR-seq to uncover dynamic and coordinated changes in chromatin states and transcriptomes during human endoderm differentiation. We also use scMTR-seq to produce lineage-resolved chromatin maps and gene regulatory networks in mouse blastocysts, revealing epigenetic asymmetries at gene regulatory regions between the three embryo lineages and identifying Trps1 as a potential repressor in epiblast cells of trophectoderm-associated enhancer networks and their target genes. Together, scMTR-seq enables investigation of combinatorial chromatin landscapes in a broad range of heterogeneous samples, providing insights into epigenetic regulatory systems.
In vitro maturation is an essential tool in reproductive technologies, though its impact on oocyte quality remains a concern. This study shows that in vitro maturation alters gene expression and DNA methylation in bovine oocytes compared to in vivo matured oocytes, potentially compromising oocyte quality and developmental competence.