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Welcome to the Sibley Lab

We have moved to Edinburgh University!

Welcome to the Sibley Lab

Find out all about us

Welcome to the Sibley Lab

Find out all about us


Our research

Since joining Imperial College London as an independent Safra fellow in 2015, Dr Sibley has established a research group that aims to understand how RNA is regulated in the central nervous system in both health and disease. A diverse range of wet and dry-lab techniques are used to achieve this. Accordingly, the group is positioning itself to work at the interface of systems biology, RNA biology and molecular neuroscience. The lab moved to Edinburgh University in May 2019 with the support of the Wellcome Trust, Royal Society and Simons Initiative for the Developing Brain.

Master Regulators

A main focus of the group is to use a combination of functional genomics and computational approaches to research master regulators in both post-mortem tissue and human cell models of neurological disease. Specifically, we define and explore target networks of both transcription factors and RNA-binding proteins. This is with the aim of identifying target networks that are perturbed in disease and which contribute to neurological disease phenotypes. In parallel, we are using computational models to understand how genomic variation impacts on regulator-target networks. Ultimately we plan to use our network models to predict the interactions that might be corrected to allow phenotypic recovery.

Cryptic Splicing

Concomitantly, we explore the disease dysregulation of the numerous un-annotated and non-canonical features of the transcriptome that have been reported in recent years. Among others this includes unconventional RNA processing events such as cryptic splice sites, recursive sites, microexons and circular RNAs. Indeed, much remains to be learned about the biological functions, biogenesis mechanisms and disease contributions of these fascinating, un-conventional and CNS-enriched transcripts. In particular we are exploring examples intrinsically linked to disease mechanisms, whilst we are testing whether any of these events can help explain disease-associated genetic variation lying outside of the exome.

Methodology

Experimentally, in addition to standard molecular biology approaches and cell culture methods, we employ the functional genomics techniques of individual nucleotide resolution UV-crosslinked immuno-precipitation (iCLIP) of RNA-binding proteins, exonuclease chromatin immuno-precipitation (ChIP-exo) of DNA-binding proteins, and RNA sequencing of the transcriptome. Importantly, both traditional RNA seq approaches and single-cell transcriptome-profiling are employed. Computational methods include weighted gene co-expression network analysis, computational inference of master regulator networks, expression quantitative trait loci analysis, and integrative modelling of iCLIP and ChIP-exo datasets.

Experimental systems

We are focussing our efforts on increasing understanding of motor neurone disease (MND) and autism spectrum disorder (ASD), whilst we primarily work with human post-mortem datasets and human cellular models. Specifically we utilise public datasets from the GTEx, CommonMinds, and UK brain expression consortia to generate our network models. We experimentally follow up our findings in human induced pluripotent stem cells differentiated into neurons and astrocytes in collaboration with Dr Rickie Patani at the Francis Crick Institute. Moreover, we are working to establish an efficient and direct differentiation of human fibroblasts into neural models. These will be used to dissect how these cells are perturbed in disease.

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Million reads sequenced

Publications

Have a look at what we've been up to. Click on the details to be taken to the article.


Our Team

Future jobs will be posted on the Edinburgh jobs portal and jobs.ac.uk, whilst we will additionally promote posts via our twitter account. Please contact Chris for more details via the form below. We also welcome prospective applications from undergraduate and masters students wishing to work with us in the meantime

    • Dr Chris Sibley

      Principal Investigator

      Following a B.A in Physiological Sciences and a M.Sc in Neuroscience both at the University of Oxford, Chris completed his DPhil at Oxford University in the lab of Professor Matthew Wood. He then spent four years as a post-doc with Professor Jernej Ule; first at the MRC's Laboratory of Molecular Biology in Cambridge, then at the UCL institute of Neurology in London. During this time he spent a year as a visiting post-doctoral fellow in the Systems Biology group of Dr Mike Inouye at the University of Melbourne. This diverse training allowed Chris to establish a group at Imperial in 2015 that spanned basic molecular biology, functional genomics and systems biology. In 2019 the lab moved to Edinburgh University with support of a Royal Society and Wellcome Trust funded fellowship. Chris is a keen runner, cyclist and kite-surfer outside of research.

    • Edinburgh University

      George Square

      Our lab is part of Edinburgh University, a university that is consistently ranked within the top 25 universities of the world. The university spans several locations across Edinburgh, and we are based between George Square and the Kings Buildings

    • The Sibley Lab

      IQB3, SIDB

      We are part of the Institute of Quantitative Biology, Biochemistry and Biotechnology (IQB3), and the Simons Initiative for the Developing Brain (SIDB). We are primarily located in 1 George Square, and are in close proximity to Discovery Brain Sciences and the School of Informatics. We additionally work closely with groups at the CH Waddington building at the Kings Buildings


Collaborators


Our Funding

We thank the following organisations for the generous current funding of the research being carried out in the Sibley lab

The Wellcome Trust
  • Projects Funded:
  • ALS transcriptomics
  • Single-cell RNA profiling
  • Master regulators
  • iCLIP / RNA networks
The Royal Society
  • Projects Funded:
  • ALS transcriptomics
  • Stem cell models
  • Cryptic splicing
  • CRISPR/Cas9 screens
The Simons Foundation
  • Projects Funded:
  • Single-cell RNA profiling
  • ASD transcriptomics
  • CRISPR/Cas9 screens
  • Converging mechanisms


Past Funding

Edmond J. Safra Foundation
  • Projects Funded:
  • ALS transcriptomics
  • iCLIP / ChIP-exo
  • Cryptic splicing
  • RNA networks
NIHR Biomedical Research Centre
  • Projects Funded:
  • Single-cell sequencing
  • ALS transcriptomics
  • Cryptic splicing
  • ALS iCLIP
The MND association
  • Projects Funded:
  • Cryptic splicing
  • RBP regulation
  • Biomarkers
  • iCLIP

Comments on our work


The Sibley Lab Blog

We are committed to the public engagement of our work so we will blog about our news and research on a regular basis. Please keep coming back to find out the latest lab developments. You can also follow us through our Twitter account

Welcome to our new website

We'll be updating the site and blogging regularly, so please keep returning to find out more about us

by Chris | 2 September 2016

We are now live on Twitter!

We will use twitter to preview our work, announce lab news, and let you know what's interesting us

by Chris | 8 September 2016

Wellcome Seed Award

I'm pleased to say we were successful in our bid for a Wellcome Trust Seed Award to study master regulators with various computational & experimental approaches!

by Chris | 7 December 2016

NIHR BRC grants

We were delighted to be awarded two grants through the NIHR Biomedical Research Centre to study the transcriptomic signatures of ALS and to develop single-cell drop-seq!

by Chris | 5 June 2017

Sir Henry Dale Fellowship

I'm delighted to announce we are moving to Edinburgh University following award of a Sir Henry Dale fellowship from the Wellcome Trust and the Royal Society.

by Chris | 29 April 2019



Contact Us



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Find us on the map

Our address

1 George Square
Edinburgh University
Edinburgh
EH8 9JZ
United Kingdom

Get in contact

chris.sibley@ed.ac.uk
https://www.ed.ac.uk/profile/dr-chris-sibley/