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Welcome to the Sibley Lab

Find out all about us

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 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.

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 are exploring 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 contributions to disease of these fascinating, un-conventional and CNS-enriched transcripts. In particular we are exploring examples which are intrinsically linked to disease mechanisms, whilst we are interested to see if any of these events can help explain disease-associated genetic variation which lies 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 drop-seq 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 Alzheimer's disease aetiology, 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 motor neurons in collaboration with Dr Rickie Patani at the UCL institute of Neurology. Moreover, we are working to establish an efficient and direct differentiation of human fibroblasts into motor neurons. These will be used to dissect why these cells are perturbed in MND.

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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

We are presently a small group and will be looking to expand soon. We 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, Dr Sibley 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 also spent a year as a visiting post-doctoral fellow in the Systems Biology group of Dr Mike Inouye at the University of Melbourne. Following his diverse training his research area spans from basic molecular biology to functional genomics to systems biology. Outside of research he is a keen runner, cyclist and kite-surfer

    • Imperial College London

      Hammersmith Campus

      Our lab is part of Imperial College London, a university that is consistently ranked within the top 10 universities of the world. The university spans several locations across London, and we are based on the Hammersmith Campus near White City

    • Division of Brain Sciences

      Burlington Danes Building

      We are part of the Department of Medicine within its Brain Sciences Division. We are located in the Burlington Danes Building which is immediately adjacent to the MRC Clinical Sciences Centre and Hammersmith Hospital. The building was completed in 2007 and has modern lab and office space.


 

Our Collaborators


Our Funding

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

The Wellcome Trust
  • Projects Funded:
  • Master Regulators
  • Genomic variation
  • Network inference
  • iCLIP / ChIP-exo
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

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


Contact Us



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Our address

Division of Brain Sciences
Burlington Danes Building
Hammersmith Hospital Campus
Imperial College London
Du Cane Road
London
W12 0NN
United Kingdom

Get in contact

c.sibley@imperial.ac.uk
www.imperial.ac.uk/people/c.sibley