Nathan Skene

Nathan Skene

Lecturer and UKDRI Group Leader

UK Dementia Research Institute

Imperial College

I am a lecturer at Imperial College’s Department of Brain Sciences and a group leader at the UK Dementia Research Institute. I initially came to Imperial as an independent Safra research fellow. My interests lie in using human genetics to gain insight into the neurobiology of brain disorders and cognitive traits. Currently I am focused on identifying the causal cell types underlying complex genetic traits. The motivation for this is that traditional approaches to science have been unable to yield definitive answers on which cell types are the primary cause of major diseases, such as Schizophrenia or Alzheimers. For instance, as the primary pathology in Alzheimers is neuronal/synapse loss, it was reasonably assumed for many years that the cause was neuronal, however analysis of genetic associatons shows that most of the causal genes are expressed in microglia.

I did my postdoctoral research at the Karolinska Institutet (KI) where I worked with Jens Hjerling-Leffler as part of the Functional Neuromics project. At KI we adapted single cell disassociation protocols such that we could obtain sufficient numbers of healthy interneurons from adult mice that we could catalogue the full complement of GABAergic cell types found in the CA1 region of the hippocampus. This work formed part of a broader effort to map all the cell types in the mouse nervous system using single cell RNA-sequencing (the completed atlas can be viewed here). To enable greater insight into which of these cell types play a role in human disease/cognition we begun collaborating with Patrick Sullivan’s psychiatric genetics team: together we established the methods which enabled us to map the cell types underlying Schizophrenia, Major Depression, IQ, Neuroticism, Alzheimer’s and Insomnia. We released the MAGMA_Celltyping package to enable others to apply this method to future GWAS studies. The KI single cell superset data which we used for cell type mapping is available here.

I gained an undergraduate degree in Artificial Intelligence and Cybernetics from the University of Reading in 2008, followed by an MPhil at the University of Cambridge in Computational Biology in 2009. I went onto do a PhD in Molecular Biology at the Wellcome Trust Sanger Institute working with Prof Seth Grant. During this time I worked on the Genes to Cognition programme, analysing the transcriptomic changes seen in a mice carrying a wide range of synaptic mutations.

Following my PhD I worked at the University of Edinburgh, where I studied how postnatal gene expression changes influence the onset of psychiatric disorders. At this time I developed a method (Expression Weighted Celltype Enrichment) which made it possible to show that microglia are the celltype whose expression profile best explains the rare & common variant’s associated with Alzheimer’s disease.

Education

  • PhD in Molecular Biology, 2014

    Wellcome Trust Sanger Institute, University of Cambridge

  • MPhil in Computational Biology, 2009

    University of Cambridge

  • BSc in Artificial Intelligence and Cybernetics, 2008

    University of Reading

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