Skip to main content
Funded Studies

Combining Mass Spectrometry with Genetic and Pharmacological Approaches to Discover and Validate LRRK2 Substrates

Much recent work has suggested that comprehending the biological properties of an enzyme termed LRRK2 that is mutated in about one percent of all Parkinson’s disease patients, will be crucial for better understanding of the molecular causes of Parkinson’s disease as well as designing new strategies to better treat this condition. Our objective is to deploy the state of the art molecular, technological, genetic and clinical expertise from six world leading researchers based in the United States, United Kingdom and Germany as well as the GlaxoSmithKline pharmaceutical company to undertake studies to identify and characterise the key physiological targets of LRRK2.

Project Description:
We plan to employ genetically modified pre-clinical models in which the LRRK2 enzyme is disrupted and undertake detailed analysis using state of the art technology called mass spectrometry to identify sets of proteins in pre-clinical tissues that are controlled by LRRK2. We will then undertake follow up studies to better understand how these proteins are controlled by LRRK2 and study whether we can exploit these findings to better understand how mutations in LRRK2 cause Parkinson’s disease in humans. We hope that this new molecular understanding of LRRK2 biology will provide us with a framework of knowledge that will lead to new ideas and accelerate our ability to devise improved diagnosis and treatment of Parkinson’s disease in the future.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
We hope that the discoveries and tools we generate in this project will be of great relevance to researchers as well as many pharmaceutical companies developing and evaluating new treatments of Parkinson’s disease based on targeting the LRRK2 enzyme. This research project has the potential to accelerate pre-clinical as well as clinical evaluation of potential drugs that target the LRRK2 enzyme for the treatment of Parkinson’s disease. Overall this research could aid and speed up the development of improved treatments for Parkinson’s disease

Anticipated Outcome:
We aim to produce a molecular framework of knowledge that better explains the molecular mechanism by which LRRK2 operates and how mutations in this enzyme might promote the development of Parkinson’s disease. This work should be useful in helping many pharmaceutical companies working in this area to better characterize the potential drugs that they are developing that target the LRRK2 enzyme for the treatment of Parkinson’s disease. These tools and methods will greatly facilitate the ability of researchers and pharmaceutical companies to work out more quickly what drugs are the most effective at targeting the LRRK2 enzyme.



  • Jarrod A. Marto, PhD

    Boston, MA United States

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

    London United Kingdom

  • Alastair D. Reith , PhD

    Stevenage United Kingdom

  • Matthias Trost, PhD

    Dundee United Kingdom

  • Dario Alessi, PhD

    Dundee United Kingdom

  • Nathanael Gray, PhD

    Boston, MA United States

Discover More Grants

Within the Same Program

Within the Same Funding Year

We use cookies to ensure that you get the best experience. By continuing to use this website, you indicate that you have read our Terms of Service and Privacy Policy.