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Funded Studies

Mapping the PD Brain: Oligomer-driven Functional Genomics

Study Rationale:
To determine the molecular and cellular process that lead to PD, a powerful approach is to single out and study the cells where the disease originates. To achieve this goal, we use alpha-synuclein oligomers as a cellular biomarker to identify the right cells. We will then apply state-of-the-art genomic and genetic analyses to identify genes and proteins that form the disease pathways. We can then determine the difference between cause and effect by using human cell models derived from induced pluripotent stem cells.

Hypothesis:
We hypothesize that alpha-synuclein oligomers can be used as cellular biomarkers to identify the specific cells where the disease processes begin, thus making their targeted study possible.

Study Design:
By detecting the presence of alpha-synuclein oligomers, we will identify neuronal and non-neuronal cells in the human brain at different stages of disease, which we will then study using state-of-the-art single cell genomic and transcriptomic methods. This will allow us to build a comprehensive and detailed picture of the genes and molecular processes that underlie the disease, which we will then prioritize using network theory and our knowledge of the current and emerging genetic factors. Using a human model system (iPSC) we will be able to distinguish cause and effect and deliver new targets for therapeutics, diagnostics and biomarkers of disease.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
This interdisciplinary program, combining physical chemistry, computational modelling, genetics and neurobiology, will allow us to much more fully understand the reasons behind why some cells succumb and other resist the pathological processes. Our findings will offer opportunities for accurate markers of disease status, progression and validated targets for biopharma to develop novel therapies.


Researchers

  • Nicholas William Wood, MbChB, PhD, FRCP, FMedSci

    London United Kingdom


  • Sonia Gandhi, BMBCh, PhD

    London United Kingdom


  • Steven F. Lee, DPhil

    Cambridge United Kingdom


  • Mina Ryten, MD, PhD

    London United Kingdom


  • Michele Vendruscolo, PhD

    Cambridge United Kingdom


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