Exeter Neuroscience Seminar Series 6 September, 2016 16:00 – 18:00 White Hart Inn, 66 South Street, Exeter, EX1 1EE Mick Craig – Using network oscillations to probe neural circuit function Mick’s main interest is studying the cellular circuitry that enables different regions of the brain synchronise their activity over long distances, with a particular focus on […]
Friday the 3rd of June saw a group of students and post-docs from our group attend the 5th annual Human Methylation Array Meeting at King’s College London. PhD student Sarah Marzi was part of the organising committee of this popular meeting designed to bring together members of the scientific community all working with the same technology to discuss different data analysis approaches in a wide range of diseases. 134 researchers from around the world were in attendance to listen to Keynote Speaker Holger Heyn from CNAG-CRG Barcelona and 12 other talks selected from submitted abstracts. Eilis Hannon and Adam Smith both gave updates of their work on DNA methylation and hydroxymethylation in schizophrenia and Alzheimer’s disease respectively. Two placement students from the Medical Sciences BSc course at Exeter University, Bethany Crawford and Olivia Knox, celebrated a very successful and productive year with the Complex Epigenetics group by presenting posters of their projects. Congratulations to Olivia who was awarded the best Poster prize for her work entitled “A longitudinal study of DNA methylation changes associated with major surgery.”
A new paper from our group published in Genome Biology characterizes the distribution of DNA hydroxymethylation (5hmC) in two regions of the human brain. We used oxidative bisulfite (oxBS) treatment with the Illumina Infinium 450K BeadArray to quantify genome-wide patterns of 5hmC in the prefrontal cortex and cerebellum. Distinct patterns of 5hmC were identified in each brain region, with notable differences in the genomic location of the most hydroxymethylated loci between these brain regions. This study demonstrates the utility of combining oxBS-treatment with the Illumina 450k methylation array to quantify 5hmC across the genome and the potential utility of this approach for epigenomic studies of brain disorders.
Our study looking at genetic influences on DNA methylation in the developing human brain was published online today in Nature Neuroscience. The study, led by Dr Eilis Hannon, identified >16,000 fetal brain mQTLs which were primarily cis-acting, enriched in regulatory chromatin domains and transcription factor binding sites, and showed substantial overlap with genetic variants that are also associated with gene expression in the brain. Of note, fetal brain mQTLs were enriched amongst risk loci identified in a recent large-scale genome-wide association study (GWAS) of schizophrenia, a severe psychiatric disorder with a hypothesized neurodevelopmental component. Our data show that mQTLs can be used to refine GWAS loci through the identification of discrete sites of variable fetal brain methylation associated with disease-associated risk variants. Our data is freely available to the wider research community via an online database
Dr Chloe Wong has received funding and is the Principal Investigator for a project entitled ‘Epigenetic trajectories of biological response to adolescent psychosocial stress: A novel longitudinal study of discordant monozygotic twins.’ This is one of eight projects, funded by the ESRC and the BBSRC, which combines biological and social sciences to uncover the long term health impacts of early life experiences.
To celebrate the launch of our new Pacific Biosciences sequencer, funded by the MRC Clinical Research Infrastructure scheme, we’d like to invite you to a special one-day meeting. It will be held in at the RILD building in Exeter on the 1st September 2015. We have a great line-up of international speakers.
Katie Lunnon has led a successful application to the Alzheimer’s Society to fund a project building on our previous studies of DNA methylation in Alzheimer’s disease brain. The project will aim to combine data from multiple studies across the world, and integrate findings with genetic data on the same patients.
The first set of twins who will be part of the new Peninsula Pre/Perinatal Twins Research Bank (PTRB) have been born. The PTRB has been established to enable us to study how growth in the womb can influence health and disease across the life-course. For more information, go to the PTRB page.
Pilot research awards have been awarded to PhD researchers Matt and Adam respectively by the recently established Alzheimer’s Research UK (ARUK) Southwest Network. Both studies aim to improve our current understanding of the dynamic epigenetic landscape and its association with the onset and progression of Alzheimer’s pathology. Matt’s grant will focus on the expression of mitochondrial-encoded genes in post-mortem brain, to determine whether changes in these genes are associated with disease. Adam’s project will focus on isolating cell populations from post-mortem brain tissue using fluorescent antibody based cell sorting (FACS).
In collaboration with Nick Allen at the University of Cardiff, Vasanta Subramanian at the University of Bath, and James Hodge and Caroline Relton at the University of Bristol we have been awarded a GW4 accelerator award to investigate the functional consequences of epigenetic changes previously identified in Alzheimer’s disease brain by our group. Together we will establish novel genetic and epigenetic editing techniques and investigate the function of the ANK1 gene in Drosophila and human cellular models. GW4 is an alliance which combines the intellectual capacity and physical resources of the four leading research-intensive universities in the South West of England and Wales: Bath, Bristol, Cardiff and Exeter.