Life Sciences Research for Lifelong Health

Simon Andrews

Simon Andrews did his first degree in Microbiology at the University of Warwick.  After a breif 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.

Latest Publications

Gender Differences in Global but Not Targeted Demethylation in iPSC Reprogramming.
Milagre I, Stubbs TM, King MR, Spindel J, Santos F, Krueger F, Bachman M, Segonds-Pichon A, Balasubramanian S, Andrews SR, Dean W, Reik W

Global DNA demethylation is an integral part of reprogramming processes in vivo and in vitro, but whether it occurs in the derivation of induced pluripotent stem cells (iPSCs) is not known. Here, we show that iPSC reprogramming involves both global and targeted demethylation, which are separable mechanistically and by their biological outcomes. Cells at intermediate-late stages of reprogramming undergo transient genome-wide demethylation, which is more pronounced in female cells. Global demethylation requires activation-induced cytidine deaminase (AID)-mediated downregulation of UHRF1 protein, and abolishing demethylation leaves thousands of hypermethylated regions in the iPSC genome. Independently of AID and global demethylation, regulatory regions, particularly ESC enhancers and super-enhancers, are specifically targeted for hypomethylation in association with transcription of the pluripotency network. Our results show that global and targeted DNA demethylation are conserved and distinct reprogramming processes, presumably because of their respective roles in epigenetic memory erasure and in the establishment of cell identity.

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Cell reports, 18, 2211-1247, 1079-1089, 2017

PMID: 28147265

DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids.
Canovas S, Ivanova E, Romar R, García-Martínez S, Soriano-Úbeda C, García-Vázquez FA, Saadeh H, Andrews S, Kelsey G, Coy P

The number of children born since the origin of Assisted Reproductive Technologies (ART) exceeds 5 million. The majority seem healthy, but a higher frequency of defects has been reported among ART-conceived infants, suggesting an epigenetic cost. We report the first whole-genome DNA methylation datasets from single pig blastocysts showing differences between in vivo and in vitro produced embryos. Blastocysts were produced in vitro either without (C-IVF) or in the presence of natural reproductive fluids (Natur-IVF). Natur-IVF embryos were of higher quality than C-IVF in terms of cell number and hatching ability to. RNA-Seq and DNA methylation analyses showed that Natur-IVF embryos have expression and methylation patterns closer to in vivo blastocysts. Genes involved in reprogramming, imprinting and development were affected by culture, with fewer aberrations in Natur-IVF embryos. Methylation analysis detected methylated changes in C-IVF, but not in Natur-IVF, at genes whose methylation could be critical, such as IGF2R and NNAT.

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eLife, 6, 2050-084X, , 2017

PMID: 28134613

Deletion of the Polycomb-Group Protein EZH2 Leads to Compromised Self-Renewal and Differentiation Defects in Human Embryonic Stem Cells.
Collinson A, Collier AJ, Morgan NP, Sienerth AR, Chandra T, Andrews S, Rugg-Gunn PJ

Through the histone methyltransferase EZH2, the Polycomb complex PRC2 mediates H3K27me3 and is associated with transcriptional repression. PRC2 regulates cell-fate decisions in model organisms; however, its role in regulating cell differentiation during human embryogenesis is unknown. Here, we report the characterization of EZH2-deficient human embryonic stem cells (hESCs). H3K27me3 was lost upon EZH2 deletion, identifying an essential requirement for EZH2 in methylating H3K27 in hESCs, in contrast to its non-essential role in mouse ESCs. Developmental regulators were derepressed in EZH2-deficient hESCs, and single-cell analysis revealed an unexpected acquisition of lineage-restricted transcriptional programs. EZH2-deficient hESCs show strongly reduced self-renewal and proliferation, thereby identifying a more severe phenotype compared to mouse ESCs. EZH2-deficient hESCs can initiate differentiation toward developmental lineages; however, they cannot fully differentiate into mature specialized tissues. Thus, EZH2 is required for stable ESC self-renewal, regulation of transcriptional programs, and for late-stage differentiation in this model of early human development.

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Cell reports, 17, 2211-1247, 2700-2714, 2016

PMID: 27926872

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Latest Publications

Two Mutually Exclusive Local Chromatin States Drive Efficient V(D)J Recombination.

Bolland DJ, Koohy H, Wood AL

Cell reports
15 2211-1247:2475-87 (2016)

PMID: 27264181

RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence.

Galloway A, Saveliev A, Łukasiak S

Science (New York, N.Y.)
352 1095-9203:453-9 (2016)

PMID: 27102483

HiCUP: pipeline for mapping and processing Hi-C data.

Wingett S, Ewels P, Furlan-Magaril M

F1000Research
4 2046-1402:1310 (2015)

PMID: 26835000

Pervasive polymorphic imprinted methylation in the human placenta.

Hanna CW, Peñaherrera MS, Saadeh H

Genome research
1549-5469: (2016)

PMID: 26769960

Ageing is associated with molecular signatures of inflammation and type 2 diabetes in rat pancreatic islets.

Sandovici I, Hammerle CM, Cooper WN

Diabetologia
59 1432-0428:502-11 (2016)

PMID: 26699651