Dr Chris Sibley

Sir Henry Dale Fellow

Biography

Background

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.

 

Undergraduate teaching

2019 – present:   Co-organisor and lecturer on Gene Expression course:

  • Pre-mRNA splicing (3 lectures).
  • Marking of exams.

Project students

  • Two wet lab Honours students implementing iCLIP to study ALS-associated RBPs (2020) 
  • Two dry lab Honours student investigating gene / splicing regulatory networks using single cell RNA-seq datasets (2020/21)
  • One dry lab M.Sc student establishing network models of RBP activity (2021)

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)

Postgraduate teaching

Postgraduate advisor - Institute of Quantitative Biology, Biochemistry and Biotechnology

Open to PhD supervision enquiries?

Yes

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

Current staff

Dr Aida Cardona-Alberich (Post-doctoral research associate)

Dr Sarah Pearce (Post-doctoral research associate)

Current students

Manon Tourbez (PhD - Simons Initiative for the Developing Brain PhD Studentship)

Olivia Rifai (PhD - Wellcome Trust Translational Neuroscience PhD programme)

Orjona Taso (PhD - MRC Precision Medicine programme)

Puzhen Xia (Systems and Synthetic Biology masters student)

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

University of Edinburgh: 3 x SBS Honours students 

Past staff supervised

Imperial College London: Karen Davey (Research assistant), Daniel Chaves (Post-doctoral research associate)

Research summary

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.

Key techniques:

  • iCLIP 
  • 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).
- ISSF3 fund (2020-2021)
- Royal Society Research Grant (2020-2021)

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)

View all 31 publications on Research Explorer

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