Dr Sam Washer is a Postdoctoral Research Fellow who joined the lab in 2020 to research and develop a genome wide CRISPR screen in iPSC derived microglia to elucidate the role of microglial genetics in Alzheimer’s Disease and Parkinson’s.
From genome wide association studies we have identified a plethora of genes which lead to an increased risk of developing of Alzheimer’s disease or Parkinson’s. With advances in genetic technologies we have identified that some of these risk genes are expressed in the brain within microglia, the cells responsible for “mopping up” dead cells and debris through phagocytosis. However, as with most genes, we have very little knowledge about the role they play in the symphony of the cellular response to pathogens and debris. The standard approach is to remove or “knock-out” one gene at a time and perform a very stringent set of phenotypic assays to assess the role of the gene, however this is very time consuming and laborious and assumes you already have a vague idea what the gene of interest does. Sam’s project aims to address this problem by performing genetic knockout of all genes at once in a massively parallel way to screen phenotypes of interest in relation to microglial function, with the overall aim of identifying novel targets for potential treatments and further exploration. This is a highly collaborative project between Dr Sally Cowley (James Martin Stem Cell Facility), Dr Daniel Ebner (Target Discovery Institute), and Dr Andrew Bassett (Wellcome Trust Sanger Institute), in collaboration with Open Targets (https://www.opentargets.org/).
Prior to joining the lab Sam graduated from the University of Exeter in 2016 with a BSc in Medical Sciences with a Professional Training Year, having spent a year at Newcastle University. At Newcastle he researched the genetics of cardiovascular development and the role of alternative splicing in planar cell polarity in zebrafish. Alongside this he generated knockout zebrafish lines using the relatively new technique (at the time) CRISPR/Cas9. Sam enjoyed the South West so much he remained at Exeter for his PhD (2016-20) with Dr Emma Dempster and Professor Jonathan Mill in the Complex Disease Epigenomics Group. Here he translated his knowledge of genetic CRISPR techniques to epigenetic markers, specifically DNA methylation. During his PhD he developed a CRISPR/Cas9 method for editing DNA methylation in cell models to examine how DNA methylation regulates gene expression in neuropsychiatric disorders including Schizophrenia and Alzheimer’s disease.
Sam’s ORCID ID: https://orcid.org/0000-0003-4004-8984