Dr Chris Sibley
Sir Henry Dale Fellow
1 George Square
- Post code
- EH8 9JZ
2002 - 2005 B.A. Physiological Sciences, University of Oxford, UK
2005 - 2006 M.Sc Neuroscience, University of Oxford, UK
2006 - 2010 DPhil Medical Sciences, University of Oxford, UK
2011 - 2013 Post-doctoral fellow, MRC Laboratory of Molecular Biology, Cambridge, UK
2013 - 2014 Post-doctoral fellow, UCL Institute of Neurology, London, UK
2014 - 2015 Visiting research fellow, Department of Pathology, Melbourne University, Aus
2015 - 2019 Edmond Lily Safra fellow, Imperial College London, UK
2019 - Sir Henry Dale fellow, School of Biological Sciences, Edinburgh, UK
Summary: Since joining Imperial College London as an independent fellow in 2015, I have 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, whilst the translational research is principled upon core concepts of basic mammalian RNA biology. Accordingly, the group is positioned to work at the interface of systems biology, RNA biology and molecular neuroscience. The lab moved to the University of Edinburgh in May 2019 with the support of the Wellcome Trust and Royal Society.
2019 – present: Lecturer on Gene Expression course:
- Pre-mRNA splicing (3 lectures).
- Marking of exams.
- Two wet lab Honours students implementing iCLIP to study ALS-associated RBPs (2020)
- One dry lab Honours student investigating gene / splicing regulatory networks using single cell RNA-seq datasets (2020)
Past international courses
- Organising committee member for three EMBO workshops on iCLIP (2 x Mainz - Germany, Barcelona - Spain)
- Invited tutor at Centre for Genomic Regulation (CRG) workshop on iCLIP & Ribosome profiling (Barcelona - Spain)
Open to PhD supervision enquiries?
Areas of interest for supervision
- RNA processing in neurological disease
- Modelling of RNA-binding protein activity
- Stem cell models of neurological disease
- Single cell RNA sequencing of ALS / autism
- Single cell multi-omic technologies
Please contact to discuss potential research projects
Dr Aida Cardona-Alberich (Post-doctoral research associate)
Manon Tourbez (Research assistant)
Sienna Acciaroli - Characterising gene regulatory networks of the nervous system at cell-type resolution
Lauren Hinks - Defining the transcriptome-wide RNA interactions of MND-associated FET proteins with iCLIP
Ruairi Kelly - Defining the transcriptome-wide RNA interactions of MND-associated FET proteins with iCLIP
Past students supervised
Imperial College London: 2 x B.Sc. Biomedical Science students
University of Oxford: 2 x M.Sc. Neuroscience students, 1 x Final Honours School student in Medicine & Physiology
Past staff supervised
Imperial College London: Karen Davey (Research assistant), Daniel Chaves (Post-doctoral research associate)
Growing evidence implicates abnormal RNA metabolism as a contributing factor to the pathobiology of various neurodevelopmental and neurodegenerative diseases, yet understanding remains limited in direct context of the human condition. Addressing is expected to identify new disease mechanisms and therapeutic targets.
My lab integrates traditional and single-nuclei RNA sequencing to elucidate transcriptome-wide changes to RNA metabolism in clinically relevant post-mortem brain tissue and human induced pluripotent stem cell (hiPSC) models of neurological disease including ALS and autism. Mechanistic follow-up of key events is then carried out within hiPSC models using established molecular biology, functional genomics and systems biology methods in order to determine both their cause and consequence.
- Total RNA-seq
- Single cell RNA sequencing
- Single cell multi-omics
- Bayesian modelling
- Reverse engineering of gene regulatory networks
- Neuronal/astrocyte differentiation of induced pluripotent stem cells
Current research interests:
- Define RNA metabolism changes in direct context of human neuropathology: Molecules and networks are characterised at region, cell and pseudotemporal resolution.
- Mechanistically dissect key RNA metabolism changes causing neural cell dysfunction: Our priorities are to understand the cause and consequence of dysregulated splicing events, and to identify intrinsic master regulators driving transcriptome-wide signatures of neurological disease.
- Understand how seeminlgy diverse genetics converge on selective cell phenotypes: Meta-analysing cell-type specific transcriptomes from different genetic backgrounds is being used to functionally cluster diverse disease-associated genes by their induced cellular phenotypes.
Past research interests
- Processing of long genes in the mammalian brain
- Non-canonical RNA splicing mechanisms
- iCLIP study of the spliceosome
- RNAi based therapies for neurodegenerative disease
Affiliated research centres
Current project grants
- Wellcome Trust and Royal Society Sir Henry Dale Fellowship (2019-2024)
- Simons Initiative for the Developing Brain project grant (2019-2021)
- Rett syndrome Research Trust project grant (2020-2022, Co-I to Stuart Cobb).
Past project grants
- Wellcome Trust Seed Award (Imperial College London)
- MND Association project grant (Imperial College London)
- NIHR BRC project grant (x2, Imperial College London)
- Alzheimer’s Research-UK pump priming grant (Imperial College London)
- Edmond and Lily Safra fellowship (Imperial College London)
A systems view of spliceosomal assembly and branchpoints with iCLIP
P-TEFb activation by RBM7 shapes a pro-survival transcriptional response to genotoxic stress
Exon junction complex shapes the transcriptome by repressing recursive splicing
Identification of expression quantitative trait loci associated with schizophrenia and affective disorders in normal brain tissue
Individual nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP) to determine protein-RNA interactions
A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models
Progressive motor neuron pathology and the role of astrocytes in a Human Stem Cell Model of VCP-Related ALS
Transcript-specific characteristics determine the contribution of endo- and exonucleolytic decay pathways during the degradation of nonsense-mediated decay substrates
Insights into the design and interpretation of iCLIP experiments
Novel RNA-based strategies for therapeutic gene silencing
Lessons from non-canonical splicing