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

TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD.
White MA, Kim E, Duffy A, Adalbert R, Phillips BU, Peters OM, Stephenson J, Yang S, Massenzio F, Lin Z, Andrews S, Segonds-Pichon A, Metterville J, Saksida LM, Mead R, Ribchester RR, Barhomi Y, Serre T, Coleman MP, Fallon J, Bussey TJ, Brown RH, Sreedharan J

Amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) constitutes a devastating disease spectrum characterized by 43-kDa TAR DNA-binding protein (TDP-43) pathology. Understanding how TDP-43 contributes to neurodegeneration will help direct therapeutic efforts. Here we have created a TDP-43 knock-in mouse with a human-equivalent mutation in the endogenous mouse Tardbp gene. TDP-43mice demonstrate cognitive dysfunction and a paucity of parvalbumin interneurons. Critically, TDP-43 autoregulation is perturbed, leading to a gain of TDP-43 function and altered splicing of Mapt, another pivotal dementia-associated gene. Furthermore, a new approach to stratify transcriptomic data by phenotype in differentially affected mutant mice revealed 471 changes linked with improved behavior. These changes included downregulation of two known modifiers of neurodegeneration, Atxn2 and Arid4a, and upregulation of myelination and translation genes. With one base change in murine Tardbp, this study identifies TDP-43 misregulation as a pathogenic mechanism that may underpin ALS-FTD and exploits phenotypic heterogeneity to yield candidate suppressors of neurodegenerative disease.

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Nature neuroscience, , 1546-1726, , 2018

PMID: 29556029

Comparison of whole-genome bisulfite sequencing library preparation strategies identifies sources of biases affecting DNA methylation data.
Olova N, Krueger F, Andrews S, Oxley D, Berrens RV, Branco MR, Reik W

Whole-genome bisulfite sequencing (WGBS) is becoming an increasingly accessible technique, used widely for both fundamental and disease-oriented research. Library preparation methods benefit from a variety of available kits, polymerases and bisulfite conversion protocols. Although some steps in the procedure, such as PCR amplification, are known to introduce biases, a systematic evaluation of biases in WGBS strategies is missing.

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Genome biology, 19, 1474-760X, 33, 2018

PMID: 29544553

MLL2 conveys transcription-independent H3K4 trimethylation in oocytes.
Hanna CW, Taudt A, Huang J, Gahurova L, Kranz A, Andrews S, Dean W, Stewart AF, Colomé-Tatché M, Kelsey G

Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyte provides an attractive system to investigate these mechanisms, because extensive H3K4me3 acquisition occurs in nondividing cells. We developed low-input chromatin immunoprecipitation to interrogate H3K4me3, H3K27ac and H3K27me3 marks throughout oogenesis. In nongrowing oocytes, H3K4me3 was restricted to active promoters, but as oogenesis progressed, H3K4me3 accumulated in a transcription-independent manner and was targeted to intergenic regions, putative enhancers and silent H3K27me3-marked promoters. Ablation of the H3K4 methyltransferase gene Mll2 resulted in loss of transcription-independent H3K4 trimethylation but had limited effects on transcription-coupled H3K4 trimethylation or gene expression. Deletion of Dnmt3a and Dnmt3b showed that DNA methylation protects regions from acquiring H3K4me3. Our findings reveal two independent mechanisms of targeting H3K4me3 to genomic elements, with MLL2 recruited to unmethylated CpG-rich regions independently of transcription.

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Nature structural & molecular biology, 25, 1545-9985, 73-82, 2018

PMID: 29323282

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Latest Publications

TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD.

White MA, Kim E, Duffy A

Nature neuroscience
1546-1726: (2018)

PMID: 29556029

MLL2 conveys transcription-independent H3K4 trimethylation in oocytes.

Hanna CW, Taudt A, Huang J

Nature structural & molecular biology
25 1545-9985:73-82 (2018)

PMID: 29323282

An endosiRNA-Based Repression Mechanism Counteracts Transposon Activation during Global DNA Demethylation in Embryonic Stem Cells.

Berrens RV, Andrews S, Spensberger D

Cell stem cell
21 1875-9777:694-703.e7 (2017)

PMID: 29100015

Transcription and chromatin determinants of de novo DNA methylation timing in oocytes.

Gahurova L, Tomizawa SI, Smallwood SA

Epigenetics & chromatin
10 1756-8935:25 (2017)

PMID: 28507606

Gender Differences in Global but Not Targeted Demethylation in iPSC Reprogramming.

Milagre I, Stubbs TM, King MR

Cell reports
18 2211-1247:1079-1089 (2017)

PMID: 28147265