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Becky Carlyle

Senior Postdoctoral Research Scientist

Research Summary

My research focuses on integration of global measures of RNA (transcriptomics) and protein (mass-spectrometry proteomics) in the post-mortem human brain to understand the molecular changes that leave us susceptible to neurodegeneration and identify biomarkers of disease progression.  My current projects focus on:

1. Cerebrospinal fluid biomarkers of Alzheimer's Disease. In collaboration with colleagues at Massachusetts General Hospital and the Yale-NIDA Neuroproteomics Center, I am using data-independent mass-spectrometry to analyse the cerebrospinal fluid of 400 attendees of a neurology clinic, to identify Alzheimer's Disease specific protein signatures from individuals with varied neurological conditions

2. Neuropeptides and resilience to Alzheimer's Disease. In work funded by the Bright Focus Foundation, I am using non-tryptic mass-spectrometry to identify neuropeptides that are highly abundant in individuals who are resilient to amyloid and tau pathology, combined with work in human iPSC-derived neuronal cultures to ascertain if these peptides are actively protective of neuronal function.

3. Spatial proteomics in human post-mortem tissue. I am developing biochemical methods to fractionate human post-mortem brain tissue and mass-spectrometry to identify proteins that may change localisation in disease states.  

Biography

I received my PhD from the University of Edinburgh in 2010, where I studied the interactions between the mental illness risk gene, Disrupted in Schizophrenia 1 (DISC1) and two important neuronal enzymes; PDE4 and GSK3-beta.  Following my PhD I moved to the USA, where I spent seven years  in the Yale Department of Molecular Psychiatry, working on a range of projects including the first mass-spectrometry proteomic assay of multiple human brain regions, establishing the aged rhesus macaque as a model of early Alzheimer's Disease, and developing cell-type specific techniques for measuring protein translation rates.  In 2017 I joined Massachusetts General Hospital and Harvard Medical School Neurology, and used proteomic techniques to identify novel tissue and biofluid markers of Alzheimer's Disease and related disorders. In 2021 I returned to the UK and joined the Wade-Martins lab, where I will begin using iPSC-derived neuronal models in addition to my established post-mortem work.