Brain Research Theme
The strategic focus of the Brain Theme is to move away from a "one-by-one" approach to choosing therapeutic targets for neurological diseases, and instead to develop a suite of flexible tools for gene regulation.
This theme leverages several key technologies, including the CRISPR-Lock platform for precise RNA modulation, upstream open reading frame (uORF) disruption for controlled protein upregulation, and large language models for rapidly analysing existing ASO data from patents and literature.
The new CellXpress.ai cell culture platform will play a central role, providing an AI-enabled operating system to automate and scale complex cell culture and high-throughput testing, so we can run our experiments more easily, more reproducibly, and at much greater scale.
The development of ASOs and other biologics in this theme will directly inform the delivery requirements and target validation priorities for the Delivery Theme.
Our first projects are looking at allele-specific ASOs for encephalopathy (several ASOs across several genes), and upregulating genes associated with neurodevelopmental delay.
The Brain theme also works closely with the Delivery Theme to find better ways to deliver medicines across the blood-brain barrier.
Research projects
Automated cell culture and screening at scale
Using the CellXpress.ai platform for faster and more standardised testing of potential therapies
Downregulation
Downregulation approaches using allele-selective ASOs and exon 1 HTT-targeting siRNAs
Upregulation
Upregulation approaches using CRISPR-Lock and uORF disruption
Theme publications
Bias in HD-ISS staging introduced by the FreeSurfer cross-sectional stream: Insights from the Huntington's Disease Young Adult Study (HD-YAS)
Huntington disease: somatic expansion, pathobiology and therapeutics
Synthesis, Biological Activity, and Molecular Dynamics Simulations of LNA-Charge Neutral Linkages for Enhanced Splice-Switching Antisense Oligonucleotides
Team
Amarjit Bhomra
Operations Manager, Wood Group, University of Oxford
Dr Ross Ferguson
MRC CoRE TG Brain Theme Co-Lead
Senior Research Fellow, UCL
Dr Hans Friedrichsen
Postdoctoral Researcher, University of Oxford
Francis Grafton
DPhil Student, University of Oxford
Barney Hill
DPhil Student, University of Oxford
Chloe Holland
DPhil student, University of Oxford
Dr Marlen Lauffer
Senior Researcher, Dutch Center for RNA Therapeutics | Co-Lead, Patient Identification workgroup, N1C.
Professor Carlo Rinaldi
MRC CoRE TG Brain Theme Lead
Professor of Molecular and Translational Neuroscience, University of Oxford
Dr Thomas Roberts
MRC CoRE TG Brain Theme Co-Lead
Associate Professor, RNA Medicine Group Leader, University of Oxford
Professor Stephan Sanders
MRC CoRE TG Director
Professor of Paediatric Neurogenetics, University of Oxford
Associate Professor, University of California, San Francisco (UCSF)
Professor Sarah Tabrizi
MRC CoRE TG UCL Site Lead
Professor of Clinical Neurology & Neurogenetics
Joint Head of Department of Neurodegenerative Disease, UCL
Dr Emilie Wigdor
Postdoctoral Researcher, University of Oxford
Professor Matthew Wood
MRC CoRE TG Translation and Commercialisation Lead
Director of MDUK Oxford Neuromuscular Centre
Director of the Oxford Harrington Rare Disease Centre
Professor of Neuroscience and Deputy Head of Medical Sciences Division, University of Oxford