Lewis Laboratory


Our group investigates inherited forms of Parkinson's disease, with a particular interest in the molecular mechanisms underlying Parkinson's disease caused by mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) gene.

All about LRRK2
LRRK2 is a large (2527 amino acid - about 260kDa) protein which has a complicated, multidomain structure including two enzymatic activities - a kinase and a GTPase.

Mutations in LRRK2 are the most common genetic cause of Parkinson’s disease, and understanding the function of LRRK2 - and what mutations do to alter this - is one of the most important questions in Parkinson’s research today. We know that mutations associated with Parkinson’s cluster in the enzymatic core of LRRK2, and that many of them act to either increase or decrease the kinase and GTPase activities of this protein. We are working to try and understand the mechanics of how this occurs, using a combination of biochemical and cellular approaches in the laboratory.

ROCO protein biology
One of the ways in which we are trying to understand how LRRK2 works is by looking at some of the other proteins that belong to the same family. In particular, we have investigated the function of Death Associated Protein Kinase 1 (DAPK1) and Malignant fibrous histiocytoma amplified sequences with leucine-rich tandem repeats 1 (MASL1).

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